PESTICIDE RESIDUES IN FOOD - 1984
Sponsored jointly by FAO and WHO
EVALUATIONS 1984
The monographs
Data and recommendations of the joint meeting
of the FAO Panel of Experts on Pesticide Residues
in Food and the Environment and the
WHO Expert Group on Pesticide Residues
Rome, 24 September - 3 October 1984
Food and Agriculture Organization of the United Nations
Rome 1985
CARBOSULFAN
IDENTITY
Carbosulfan is a draft ISO common name
Chemical name: 2,3-dihydro-2,2-dimethylbenzofuran-7-yl
(dibutylaminothio)methylcarbamate
Chemical Abstracts Registry Number: 55285-14-8
Company Code Number: FMC 35001
Structural formula:
Other information on identity and properties
Empirical formula: C20H32N2O3S
Molecular weight: 380.5
Physical state: Viscous brown liquid
Vapour pressure: 0.31×10-6 Torr
Specific gravity: 1.056
Solubility:
Water 0.3 mg/l
Xylene >50%
Hexane >50%
Chloroform >50%
Methylene Chloride >50%
Methanol >50%
Acetone >50%
Formulations
Corrosion hazards: none
Storage stability: Some emulsifiable concentrate and solid
formulations are said to be stable for 6
months at 50°C, and over one year at room
temperature.
Explosive hazards: Non-explosive
Flash point: Above 38°C (closed cup method)
Shipping classification: Agricultural insecticide, liquid or solid.
RESIDUES IN FOOD AND THEIR EVALUATION
USE PATTERN
Carbosulfan is a broad spectrum carbamate pesticide closely
related to its main metabolite carbofuran, a major pesticide in its
own right. Carbosulfan is available as emulsifiable concentrates,
dusts and granular formulations (wettable powder formulations are
under development) for the control of soil and foliar pests of a
variety of commodities. It may be applied to soil or foliage and is
said to be effective through direct contact or stomach ingestion.
Foliar pests may be controlled by soil applications via systemic
action, although as discussed under "Fate of Residues" most of the
systemic activities is not due to carbosulfan per se. It is also
registered for seed treatment and may be applied from the ground or
air. Treatment may be in furrow, by band, broadcast, side dress,
pre-plant, injection or pre-emergence.
Adequate information on registered or nationally approved
pre-harvest intervals, restrictions, etc. was not provided to the
meeting. Application rates were received too late for consideration in
this evaluation, but are included in Table 1 which summarizes the
available information on use patterns for those commodities for which
residue data were also provided. Information on experimental uses in
the U.S.A. was also received although these uses do not yet represent
U.S. good agricultural practice. This information is summarized in
Table 2 for those commodities for which residue data were also
available. The information available (Tables 1 and 2 and similar
information on crops for which there were no residue data) does not
allow an estimate of MRLs based on nationally approved uses. Other
information on "suggested" uses was provided, but without safety
intervals, and it could not be determined whether these uses are
approved in any country.
Table 1. Summary of world-wide registered carbosulfan formulations
Application
Formulation rate kg
(wt/vol for a.i./ha or
Commodity Country EC and WP) (g a.i./100L) Application1
Apples Greece 25% EC (50-75) 1
Korea 25% WP 1.25 1
Taiwan 48.3 EC 0.1-2.4 (wax apple)
Brassica Taiwan 3% G 1.2 -
U.K. 10% G (50) 3
Brassica U.K. 10% G 3
(leafy)
Carrots Taiwan 5% G 3.5 -
Citrus Greece 25% EC (50-75) 1
Israel 25% EC 1.25 1
Tunisia 25% EC (50) 1
Taiwan 40 WP 0.8(lemon & orange)
48.3 EC 0.5-1 (orange)
Corn France 5% G 0.5 3
Greece 25% EC 0.5-0.6 1
Indonesia 25% ST 0.5-1% a.i./kg seed A
Pakistan 20% EC 0.1-0.2 1
Philippines 25% ST 0.2 A
Spain 5%-10% G 0.65-0.75 3
Swaziland 25% 2.5-3 C
Taiwan 3 G 1.2
Zimbabwe 25% EC 3 4
Pears Greece 25% EC (50-75)
Potato Greece 2.5% EC 0.4-0.5 1
Spain 2% D 0.5 15
25% EC 0.375-0.5 15
Yugoslavia 25% EC 1
1.5% D 1
Rice Bangladesh 20% EC 0.2-0.5 1
India 20% EC 0.2 1
Indonesia 20% EC 0.2-0.4 1
25% ST 0.5-1%/kg seed A(upland
rice)
Korea 25% EC 0.29 1
1.5% D 0.6 5
Malaysia 20% EC 0.2-0.4 1
2% D 0.6 1
Philippines 20% EC 0.2-0.25 1
150 EC 0.2 1
Table 1. (continued)
Application
Formulation rate kg
(wt/vol for a.i./ha or
Commodity Country EC and WP) (g a.i./100L) Application1
Sri Lanka 2% D 0.5 1
20% EC 0.2-0.5 1
Taiwan 1% D 0.5-1.2 C
2% D 0.8-1.2 6C
40% WP 0.3-0.4 1
48.3% EC 0.5 1
30 WP 0.45
Thailand 20% EC 1
5G 2
Sorghum France 5% G 0.5(corn extension) 3
Spain 5% G 0.45-0.75 3
10% G 0.45-0.75 3
Soybean Indonesia 20% EC 0.2-0.4 1
25% ST 0.5-1% a.i./kg seed A
Sugar beets France 5% G 0.6 3
Greece 25% EC 0.5 1
Spain 5% G 0.6-0.75 3
10%G 0.6-0.75 3
U.K. 10% G 3.0 g a.i./100m of row 3
Swedes U.K. 10% G 3
(rutabaga)
Wheat Greece 25% EC 0.4 C
1 APPLICATION RATES CODE
1. Foliar: Ground application
2. Foliar: Aerial application
3. Soil: In-furrow
4. Soil: Band
5. Soil: Broadcast
6. Soil: Sidedress
7. Soil: Pre-plant incorporated
8. Soil: Root zone injection
9. Soil: Pre-emergence
A. Seed Treatment
B. Seed Soak
C. Other
Table 2. Experimental uses in the U.S.A.1
Commodity Formulation Application (rate/restrictions)
Alfalfa 4EC2 0.125-1 lb. a.i./A; 1 spray appli./cutting;
3 appli. per season; 9 mo. crop rotation
restrictions, reed/forage restriction; Limited
to certain states.
Apples 25WP 0.125-0.5 lb a.i./A; per 100 Gal full coverage
(dilute) or 0.5-2 lb. a.i./A for concentrate
sprays.
Citrus 2.5EC3 5-60 oz. a.i./A (0.35-4.2 kg a.i./ha) full
coverage, 2-4 appli./season, depending on
specific label instructions.
Field corn 4EC 1 lb. a.i./1300 linear feet (1 acre with 40
inch row space) at plant
or
2 lb. a.i./A broadcast at plant.
OR:
4EC 0.125-0.5 lb. a.i./100 gal full cover (dilute)
or 0.5-2 lb. a.i./A for concentrates.
Sorghum 4EC 0.5 lb. a.i./20-40 gal/A to plant base.
(ground only)
or
per Gal/A for aerial 30-day graze and harvest
restrictions. 3 applications/season.
1 Uses listed are for experimental purposes and do not represent established good
agricultural practices in the U.S.A.
2 4 lb. a.i./Gal.
3 2.5 lb. a.i./Gal.
RESIDUES RESULTING FROM SUPERVISED TRIALS
Over 70 residue studies were submitted from supervised residue
trials on a variety of crops grown in America, Asia or Europe. The
data are summarized in Tables 3a-i.
Root and Tuber Vegetables
Data were available from three European countries for either
carrots, potatoes, sugar beets or rutabagas (Table 3a). Application
rates were generally consistent with the 0.5-2 kg a.i./ha foliar rates
"suggested" for sugar beets and potatoes, with the exception of the
French trials. No pre-harvest intervals were suggested. While residues
in most samples were below 0.05 mg/kg each of carbosulfan, carbofuran
and 3-hydroxycarbofuran, a significant number exceeded that level.
Maximum total carbamate residues (sum of the maxima of the three
residues in any one set of data) were: carrots <0.07 mg/kg, potatoes
0.22 mg/kg, sugar beet roots 0.71 mg/kg and rutabaga roots 0.95 mg/kg.
Carbosulfan was generally the predominant root residue from foliar
spray or in-furrow granular applications except in one rutabaga sample
where carbofuran was much the highest.
Harvest-to-analysis intervals and temperatures were not provided
in many cases. For carrots, storage was for 20 days with
refrigeration; potatoes unknown conditions (French trials) and
intervals unknown to 1 year at ±20°C (U.K.); sugar beets ±20° and
unknown to 9 months (France) and 1 month-1.5 yr., unknown temperature
(U.K.). In storage trials (see "Storage" under "Fate of Residues")
residues were constant over 21 months at -18°C (0°F), but with some
conversion of carbosulfan to carbofuran.
Brassica
Data were available (Table 3b) for head cabbage, Brussels sprouts
and cauliflower from the U.K., where the 5G formulation used in the
trials is approved for use, but information was provided too late for
the meeting to determine whether the application rates reflected
approved practice. "Suggested" uses (no interval) for vegetables are
2.5-5kg a.i./ha or EC foliar at 0.25 to 0.5 kg a.i./ha.
In all cases individual residues of carbosulfan, carbofuran, and
3-hydroxycarbofuran were <0.05 mg/kg in the portions of the
commodities to which limits normally apply, giving a total carbamate
residue below 0.15 mg/kg. Residues of 3-hydroxycarbofuran on whole
Brussels sprouts plants ranged up to 0.52 mg/kg.
Samples were stored at ±20°C for periods ranging from unknown to
1 year. In storage studies (see "Fate of Residues-In Storage") 40% of
the total residue was lost within three weeks.
Table 3a. Residues of carbosulfan and metabolites in root and tuber vegetables resulting from supervised field trials
Application Residues, mg/kg
Crop Country Year
Rate, Interval, 3-OH- FMC Reports
No. kg a.i./ha Formulation days Carbosulfan Carbofuran Carbofuran 1984
carrots France 1981 1 1 (furrow) 5G 125 <0.01(1)1 <0.01(1) <0.05(1) VII-3
potatoes France 1979 1? 1.25 not given not given <0.01(5) <0.06(5) <0.01(5) VI-5
1980 1? 25-37.5 not given 88-123 <0.01(9) <0.01(9) <0.01(9)
1981 1? 1.25-50 not given not given <0.01(15) <0.01(11) <0.05(11)
1981 1? 50 not given not given 0.16(1)
Italy 1981 1? 30 not given not given - <0.04(5) <0.05(5)
U.K. 1978 1 0.75 25EC 79-100 <0.05(8) <0.05(8) <0.05(8) VII-5 &
VI-4
1979- 1-2 0.75 25EC 66-68 <0.05(14) <0.05(14) <0.05(14) VII-5 &
80 VI-4
1980 62 0.75 25EC 14 <0.03(4) <0.01(4) <0.01(4) VII-5 &
(foliar) VI-4
28 <0.03(4) <0.01(3) <0.01(4)
0.02(1)
Table 3a (2)
Application Residues, mg/kg
Crop,
Country, Rate 3-OH-
Year No kg a.i./ha formulation Days Carbosulfan Carbofuran Carbofuran Ref.
Roots Foliage Roots Foliage Roots Foliage VII-2
Sugar
beets,
France, 172
1978 1 0.6-0.75 5G (mature) <0.05(4)1 <0.05(4) <0.05(4) <0.05(4) <0.05(4) <0.05(4)
1979 1 0.6 5G 129-132 <0.05(10) <0.05(12) <0.05(12) <0.05(12) <0.05(12) <0.05(12) VII-2
(in furrow) 0.06 (1)
0.25 (1)
1 1.8 5G 129-132 <0.05-0.1(5) <0.05(12) <0.05(12) <0.05(12) <0.05(12) <0.05(10)
(in furrow) [0.13-0.2]7(2) [0.09-0.1](2)
[0.3-0.4] (2)
1 0.6 5G 159-162 <0.05(11) <0.05(12) <0.05(12) <0.05(12) <0.05(11) <0.05(12)
(in furrow) 0.06 (1) 0.06 (1)
1 1.8 5G 159-162 <0.05(11) <0.05(11) <0.05(11) <0.05(11) <0.05(12) <0.05(8)
(in furrow) 0.06 (1) 0.07 (1) [0.06-0.13](4)
Table 3a (3)
Application Residues, mg/kg
Crop,
Country, Rate 3-OH-
Year No kg a.i./ha formulation Days Carbosulfan Carbofuran Carbofuran Ref.
Sugar
beets,
U.K., seedlings seedlings seedlings
1981
1 3.0ga.i./ 10G 40 <0.05(1)1 <0.05(1) <0105(1) VIII-
100m 8
Roots Leaves Roots Leaves Roots Leaves
1 (in furrow) 104 <0.05(1) <0.05(1) <0.05(1) <0.05(1) <0.05(1) <0.05(1)
1 (in furrow) 181 <0.05(1) <0.05(1) <0.05(1) <0.05(1) <0.05(1) <0.05(1)
1978 6 0.5(foliar 25EC 14 <0.05(2) <0.06(1) <0.05(4) <0.05(2) <0.05(4) <0.24(1) VII-
spray) 0.08(1) 0.15(1) 0.06(1) 0.3(1) 4
0.66(1) 0.21(1) 0.07(1) 0.8
1(1) 1.1
28 <0.05-0.09(4) <0.05- <0.05(4) <0.05- <0.05(4) <0.3(2)
0.11(3) 0.07(4) [0.5-0.6]7 (2)
0.47(1)
1-2 0.5 25EC 68-118 <0.05(9) <0.05(9) <0.05(9) <0.05(9) <0.05(9) <0.05(5)
(broadcast (mature) [0.08-0.13](4)
foliar
spray)
Swedes
(rutabaga),
U.K., 1981 1 1-1.2 10G 121-123 <0.05(3) <0.05(3) <0.05(2) <0.05(1) <0.05(3) <0.05(3)
(in furrow) (mature) 0.85(1) [0.4-
0.6] (2)
Table 3b. Residues of carbosulfan and metabolites in brassica and legume vegetables resulting from supervised field trials
Application Residues, mg/kg
Crop,
Country, Rate, Interval, 3-OH-
Year No. kg a.i./ha Formulation days Carbosulfan Carbofuran Carbofuran Ref.
Cabbage (head),
U.K.,
1979 1 2-3 5G 105-152 <0.05(10)1 <0.05(10) <0.05(10) VI-6&
(furrow at VII-1
seedling)
Brussels sprouts,
U.K.,
1978 1 2 (furrow 5G 131-146 <0.05(4) <0.05(4) <0.05(4) "
at transpl.)
whole plant 1 3.1 (furrow 5G 120 0.05(2) 0.05(2) 0.05-0.52(6) "
at seedling) (0.4 av.)
cauliflower,
U.K.,
1979 1 2-3 (furrow 5G 105-152 <0.05(20) <0.05(20) <0.05(20) "
(at seeding (curds)
or transplt.)
Legume Vegetables
Dry beans,
Brazil,
1983 1 0.75-1 25EC 87 <0.02(1) <0.02(1) <0.02(1) V-6
kg a.i./100
kg seed
treatment
Table 3c. Residues of carbosulfan and/or metabolites in citrus resulting from supervised residue trials
Application* Residues, mg/kg
Country, 3-Hydroxy- 3-Keto-
Year, Rate, Interval, Carbosulfan Carbofuran carbofuran carbofuran Total
Crop, No. kg a.i./ha Days Max Ave Max Ave Max Ave Max Ave Max Ave Ref.
U.S.A. 1 0.94 0 .09 .08 .06 (.04) (.01) ND** (.01)8 ND .15 .13 I-17,
(FL) (3 trials) 7 (.01) (.01) .05 (.04) (.03) (.02) (.01) (.01) (.09) (.08) 19
1979 14 ND ND .05 (.04) (.02) (.01) (.02) (.01) (.08) (.06)
28 ND ND (.03) (.03) (.01) (.01) (.01) ND (.04) (.04)
oranges 5 0.94-3.8 0 .16 .12 .28 .23 .41 .28 .09 .07 .90 .71
(10 total) 7 (.03) (.03) .26 .19 .39 .24 .12 .05 .74 .50
(3 trials) 14 (.01) ND .28 .20 .31 .23 .10 .07 .68 .53
28 ND ND .28 .21 .41 .28 .10 .07 .70 .56
4 0.94-3.8 0 .14 .12 .16 .16 .37 .34 (.02) (.02) .68 .64
(9.4 total) 7 (.02) (.02) .17 .14 .41 .38 (.04) (.04) .59 .58
(1 trial) 14 (.01) (.01) .15 .14 .31 .31 (.04) (.04) .50 .49
28 (.01) (.01) .17 .15 .34 .32 (.04) (.04) .55 .52
grapefruit 4 0.94-3.8 0 (.04) (.04) .24 .22 .35 .34 .06 .05 .67 .65
(9.4 total) 7 (.01) (.01) .20 .18 .24 .23 .05 (.04) .49 .46
(1 trial) 14 ND ND .26 .20 .28 .26 .09 .08 .62 .56
28 ND ND .17 .16 .23 .22 .05 (.04) .43 .42
Table 3c. (continued)
Application* Residues, mg/kg
Country,
Year, Rate, Interval, 3-keto- 3-OH-
Crop No. kg a.i./ha Days 7-phenol 7-phenol 7-phenol Total4 Dibutylamine 5,6,7
oranges 0 0.02 0.04 0.07 0.13 0.29 I-1,8
[0.005-0.07)7 [0.03-0.04] [0.06-0.08] [0.19-0.41]
5 (3 trials)
Note: same 7 0.03 0.03 0.06 0.12 0.25
trials as [0.14-0.36]
oranges 14 0.02 0.03 0.07 0.12 0.20
above where 5 [0.14-0.32]
applications 28 <0.005 0.04 0.06 0.10 0.21
and 3 trials (detection [0.15-0.29]
were conducted limit)
* All 2.5EC formulation
** ND = none detected = <0.01 mg/kg for individual carbamates.
Table 3c (2)
Application* Residues, mg/kg
Country, 3-Hydroxy- 3-Keto-
Year, Rate, Interval, No. of Carbosulfan Carbofuran carbofuran carbofuran Total9
Crop, No. kg a.i./ha Days Samples Max Ave Max Ave Max Ave Max Ave Max Ave Ref.
U.S.A.
(FL,TX),
1980-81,
Oranges 5 4.6 (2x) 7 6 0.06 0.02 0.63 0.53 0.58 0.47 0.20 0.18 1.37 1.19 I-3,
(Valenica) 1 (3x) 4,20
(3 trials)
oranges 4 4.6 (2x) 0 2 0.33 0.30 0.26 0.22 0.46 0.45 0.06 0.06 1.05 1.04
(Hamlin & 1 (2x) 7 4 0.05 0.05 0.24 0.21 0.65 0.50 0.08 0.07 1.00 0.83
Marrs) (2 trials) 14 2 (0.04) (0.03) 0.20 0.20 0.42 0.40 0.10 0.09 0.76 0.71
28 2 (0.02) (0.02) 0.26 0.25 0.34 0.32 0.10 0.10 0.72 0.70
grapefruit 4 4.6 (2x) 0 2 0.14 0.14 0.63 0.60 0.46 0.42 0.10 0.10 1.33 1.25
1 (2x) 7 6 0.09 (0.04) 0.69 0.40 0.53 0.36 0.25 0.13 1.56 0.93
(3 trials) 14 2 0.10 0.07 0.74 0.70 0.50 0.48 0.24 0.24 1.54 1.49
28 2 (0.02) (0.02) 0.62 0.58 0.46 0.46 0.27 0.26 1.36 1.32
3-keto- 3-Hydroxy- Total No. of
7-phenol 7-phenol 7-phenol phenolics DBA Samples Ref.
oranges 5 as above [(0.04)-0.13)]7 [(0.04)-0.09)] [0.08-0.23] [0.16-0.45] [0.43-0.64] 16 see
0.07±0.02 0.06±0.01 0.13±0.05 0.26+0.09 0.43 above
as above 4 as above [(0.04)-0.15] [(0.02)-0.09] [(0.04)-0.24] [0.10-0.55] [0.18-0.66] 12
0.09±0.03 0.05±O.02 0.15±0.09 0.29±0.10 0.45
* All 2.5EC formulation
Table 3c (3)
Application* Residues, mg/kg Ref. 1-22
Total
Country, 3-OH- 3-Keto- carbamate
year, Rate Interval, No. of Carbosulfan Carbofuran carbofuran carbofuran metabolites
crop No. kg a.i./ha Days Samples Max Ave Max Ave Max Ave Max Ave Max* Ave
USA
(CA),
1982,
oranges
(Valencia) 2 1.7 (aerial) 0 4 0.08 (0.04) 0.08 (0.04) (0.02) (0.02) (0.01) (<0.01) 0.11 0.06
2.5EC
7 4 (0.01) <0.01 0.05 (0.04) (0.02) (0.02) (0.01) (0.01) 0.08 (0.06)
14 4 (0.01) <0.01 (0.04) (0.03) (0.03) (0.02) (0.01) (0.01) (0.08) (0.06)
28 4 <0.01 <0.01 (0.01) <0.01 (0.02) (0.01) (<0.01) (<0.01) (0.03) (0.02)
* Total metabolite max. based on max. for any individual sample
CONT'D
Phenolic residues (18 samples) DBA Ref.
I-13,
0 4 All phenolics <0.01 mg/kg at (0.11) 15
[0.01-0.11]7
7 4 all intervals except one (0.17)
[0.11-0.2]
14 4 0.03 mg/kg estimated residue (0.13)
[<0.1-(0.15)]
28 4 at 0 day (0.14)
[0.11-0.18]
Table 3c (4)
Application** Residues, mg/kg Ref. 1-21
Country, 3-Hydroxy- 3-Keto-
year, Rate Interval, No. of Carbosulfan Carbofuran carbofuran carbofuran Total
crop No. kg a.i./ha Days Samples Max Ave Max Ave Max Ave Max Ave Max Ave
USA 2 1.7 0 8 1.7 0.53 0.39 0.23 0.83 0.16 0.06 (0.03) 2.3 0.94
(CA,AZ) , 7 4 0.87 0.27 0.86 0.42 0.36 0.12 0.19 0.08 2.2 0.89
1982, 14 8 0.35 0.15 0.77 0.47 0.36 0.14 0.18 0.08 1.7 0.83
oranges 28 8 0.11 (0.04) 0.31 0.26 0.22 0.08 0.08 0.05 0.55 0.43
4 1.7 0 8 0.95 0.58 0.58 0.28 0.08 (0.04) (0.04) (0.01) 1.5 0.91
7 8 0.41 0.27 0.90 0.38 0.19 0.07 0.14 0.05 1.5 0.76
14 8 0.27 0.14 0.70 0.40 0.15 0.07 0.09 0.05 1.0 0.65
28 8 0.10 (0.03) 0.51 0.29 0.09 0.05 0.06 (0.03) 0.66 0.33
* Total max. based on max. total in any one sample
** All 2.5EC formulation
Table 3c (4) (continued)
Phenolic and DBA residues
Rate
kg a.i./ 3-Hydroxy-
Cont'd ha Days Samples 7-Phenol 3-Keto-7-phenol 7-phenol Phenolics DBA Ref.
Range Ave. Range Ave. Range Ave. Range Ave.
3
0 8 (0.01)2 0.09 (0.04) ND (0.02) (0.01) ND-(0.02) (0.004) (0.02)-0.12 0.09 all studies
0.38 ± 0.24 I-
2 1.7 7 24 ND 0.17 0.05 ND- 0.06 (0.02) ND- 0.06 (0.02) (0.02)-0.25 0.09 6,7
14 8 (0.02)-0.10 0.05 ND- 0.06 (0.02) ND- 0.06 (0.02) (0.02)-0.22 0.09 [0.08-1.8]7
28 8 (0.01)-(0.04) (0.03) ND-(0.04) (0.02) ND-(0.04) (0.01) (0.01)-0.11 0.09
0 8 (0.03)-0.10 0.07 ND (0.02) (0.01) ND-(0.03) (0.01) 0.05-0.11 0.08
7 24 ND-0.11 0.05 ND-0.05 (0.02) ND-(0.03) (0.01) ND-0.19 0.08
4 1.7 14 8 ND-0.12 0.06 ND-(0.04) (0.02) ND-(0.02) (0.01) ND-0.19 0.09
28 8 ND-0.07 (0.03) ND-(0.043) (0.02) ND-(0.03) (0.01) ND-0.12 0.06
Table 3c (5)
Application Residues, mg/kg
Country,
year, Interval, 3-keto- 3-OH-
crop No. kg a.i./ha days 7-phenol 7-phenol 7-phenol DBA Ref.
USA (CA,AZ),
1982, 2 1.7 0 [<0-01-0.09]7 <0.01 <0.01 0.42 I-12,
grapefruit 2.5EC 16
formulation 7-8 [(0.03)-0.05] at all at all 0.2-0.4
intervals intervals
14 (0.02) 0.16
28 [0.01-0.03] 0.28
Table 3c (6)
Application Residues, mg/kg Ref. 1-24
Total
Country, 3-Hydroxy- 3-Keto- carbamate
year, Rate Interval, No. of Carbosulfan Carbofuran carbofuran carbofuran metabolites
crop No. kg a.i./ha Days Samples Max Ave Max Ave Max Ave Max Ave Max Ave
USA (FL), 4 l(2x) 0 4 0.09 0.06 0.36 0.30 0.57 0.44 (0.04) (0.03) 0.95 0.76
1982, 4.2(2x) 7 4 (0.01) ND 0.40 0.26 0.49 0.37 (0.04) (0.03) 0.93 0.66
2.5EC 14 4 ND ND 0.25 0.22 0.50 0.39 (0.03) (0.03) 0.74 0.64
formulation 28 4 ND ND 0.19 0.18 0.42 0.36 (0.03) (0.03) 0.64 0.57
ND = none detected = <0.01 mg/kg
Phenolic and DBA residues
3-kote 3-OH Total
7-phenol 7-phenol 7-phenol phenolics DBA (Max) Ref.
Cont'd 0 4 (0.04) (<0.01) to 0.06 0.11 0.43-0.49 I-11,
[(0.03)-0.05]7 (0.02) [0.05-0.07] 14
7 4 0.03 at all 0.09 0.13 0.41-0.48
[(0.01-0.05] intervals [0.05-0.12]
14 4 (0.02) 0.07 0.1 0.32-0.36
[0.02-0.03] [0.05-0.08]
28 4 (0.02) 0.06 0.09 0.29-0.40
[(0.02)] [0.05-0.07]
Table 3c (7)
Application Residues, mg/kg10
Country,
year, Rate, Interval, 3-Hydroxy-
crop No. kg a.i./ha Days Carbosulfan Carbofuran carbofuran Ref.
Fruit Peel Fruit Peel Fruit Peel
Italy, 2 75g/hl 0 0.67 3.9 0.48 1.1 <0.05 0.15 VI-3
1982, 25EC 0 0.71 3.5 0.47 1.7 +<0.05 0.13
oranges formulation untreated 0 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 VIII-5
14 0.96 3.4 1.07 1.9 0.07 0.31
14 0.66 1.8 0.90 1.2 0.05 0.17
untreated 14 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
28 0.46 1.3 1.51 2.3 0.15 0.19
28 0.27 1.1 0.75 1.6 0.08 0.12
untreated 28 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
42 0.30 1.2 1.09 2.6 0.06 0.36
42 0.28 0.71 0.95 1.8 +<0.05 0.23
untreated 42 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
56 0.7 2.9 0.08 0.3
56 0.25 0.4 0.67 2.2 +<0.05 <0.05
untreated 56 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05
Table 3d. Residues of carbosulfan and metabolites in pome fruit resulting from supervised field trials
Application Residues, mg/kg
country, Total
year, Rate, Interval No. of 3-Keto- 3-Hydroxy- carbamate
crop kg a.i./ha formulation Days Samples Carbosulfan Carbofuran carbofuran carbofuran metabolites** Ref.
USA (16 2.2 4EC 0 8 0.12 - 0.71 0.12 - 0.32 ND* 0.04 - 0.34 0.17 - 0.55 III-1,
trials, 8 (delayed + Average=0.52 Average=0.21 Average=0.18 Averaqe=0.39 2,6
states), dormant 4EC
1981, (1X) + 14 8 0.07 - 0.96 0.04 - 0.29 ND 0.04 - 0.31 0.08 - 0.55
apples 1.1 Average=0.36 Average=0.16 Average=0.16 Average=0.31
foliar
(3X) 28 24 0.05 - 0.96 0.03 - 0.38 ND ND - 0.33 0.33 - 0.68
Average=0.32 Average=0.16 Average=0.12 Average=0.28
2.2 4EC 0 4 0.26 - 0.56 0.25 - 0.35 ND ND - 0.05 0.27 - 0.40
(delayed Average=0.40 Average=0.29 Average=0.03 Average=0.32
dormant +
1X) + 14 4 0.11 - 0.45 0.05 - 0.14 ND ND - 0.05 0.05 - 0.19
1.1 25WP Average=0.26 Average=0.10 Average=0.03 Average=0.13
foliar
(3X) 27-28 8 0.06 - 1.60 0.04 - 0.72 ND 0.02 - 0.23 0.08 - 0.95
Average=0.50 Average=0.29 Average=0.11 Average=0.40
*ND = <0.02 mg/kg **Total carbamate max. is max. for any one sample
Table 3d. (continued)
CONTINUED Phenolic residues Dibutylamine residues
No. of
EC + EC Samples Days Range or average, corrected, mg/kg
7-Phenol 3-Keto- 3-Hydroxy- No. of Average
7-phenol 7-phenol Total Samples Days [range], mg/kg
8 0 0.23
[0.15-0.27]
Range 0- ND*-0.15 ND-0.05 ND-0.08 ND-0.24 10 14 0.22
Average 44 28 0.06 0.01 0.02 0.09 [0.09-0.37]
26 28 0.2
[<0.1-0.52]
EC + WP
Range 18 0- 0.02-0.17 ND-0.03 ND-0.06 ND-0.06
Average 28 0.06 0.01 0.02 0.02
ND = <0.01
Table 3d (2)
Application Residues, mg/kg
Country, Carbosulfan Carbofuran 3-OH-carbofuran
year, Rate, Site Site Site
crop No. kg a.i./ha Days 1 2 1 2 1 2 Ref.
Italy, 2 75 ga.i/hl 0 2.1 0.8 0.5 0.1 0.08 0.1 VIII-2
1981, (site 1) 25EC 2.5 1.7 0.5 0.2 0.3 0.1
apples 3 fomulation
(site 2) (aerial) 14 1.2 1 0.2 0.2 0.1 0.2
1.9 0.7 1.2 0.1 0.4 0.1
21 1.4 0.7 0.8 0.2 0.3 0.2
1.4 0.7 0.3 0.2 0.07 0.1
28 0.3 0.8 0.6 0.2 0.1 0.2
1 0.8 0.6 0.3 0.3 0.2
35 0.7 0.2 0.9 0.2 0.4 0.2
1.2 0.8 0.3 0.2 0.2 0.1
42 1 0.2 0.6 0.1 0.4 0.1
0.1 0.2 0.9 0.2 0.3 0.3
Table 3d (3)
Residues, mg/kg
Application Carbosulfan Carbofuran 3-Hydroxycarbofuran
country,
year, Rate, Interval Site Site Site Site Site Site
crop No. kg a.i./ha Days 1 2 3 4 1 2 3 4 1 2 3 4 Ref.
UK, 4-5 0.1 7 1 1.4 0.2 0.5 0.1 0.3 VIII-1
1980, (foliar
apples (Cox, spray to 10 2.3 0.7 0.6 0.5 0.3 0.3
Bramley, run-off) 2.1 0.7 0.6 0.2 0.3 0.2
George Cave) 25EC
formulation 13- 0.9 0.7 0.6 1.5 0.3 0.5 0.2 0.5 0.2 0.3 0.09 0.08
14 1.5 0.6 0.7 0.3 0.2 0.2
1.4 1 0.7 0.6 0.4 0.5
0.3 0.8 0.8 0.6 0.2 0.5
21 0.4 0.6 0.2 0.4 0.08 0.2
28 1 1.1 0.6 0.3 1.1 0.5 0.3 0.3 0.8 0.6 0.1 0.2
0.8 0.6 0.8 0.4 0.7 0.5
35 0.2 0.4 0.2 0.3 0.2 0.2
42 0.91 0.6 0.8 0.5 0.5 0.4
0.7 0.2 0.5 0.3 0.3 0.3
Table 3d (4)
Residues, mg/kg
Application
Country, Total
year, Rate, Interval No. of 3-Keto- 3-Hydroxy- carbamate
crop kg a.i./ha formulation Days Samples Carbosulfan Carbofuran carbofuran carbofuran metabolites** Ref.
USA (6 2.2 4EC 0 0.18 - 1.07 0.04 - 0.11 ND* ND - 0.06 0.06 - 0.16 III-11
trials, delayed Average=0.58 Average=0.06 Average=0.04 Average=0.11
4 states), dormant +
1981-82, 1X + 1.1 14 ND - 0.08 ND - 0.04 ND 0.05 - 0.09 0.05 - 0.10
pears foliar 2X 4EC Average=0.05 Average=0.03 Average=0.06 Average=0.09
28 ND - 0.23 ND - 0.03 ND 0.02 - 0.08 0.02 - 0.09
Average=0.08 Average=ND Average=0.05 Average=0-06
2.2 4EC 0 0.38 - 0.92 0.04 - 0.08 ND ND - 0.04 0.04 - 0.12
delayed Average=0.67 Average=0.07 Average=0.02 Average=0.08
dormant +
1X + 1.1 14 0.12 - 0.19 0.02 - 0.05 ND 0.03 - 0.06 0.05 - 0.11
foliar 2X 25WP Average=0.15 Average=0.03 Averaqe=0.04 Average=0.08
28 0.05 - 0.17 ND-0.03 ND 0.02 - 0.05 0.02 - 0.08
Average=0.09 Averace=0.02 Average=0.03 Average=0.05
3-Keto 3-Hydroxy Total Ref.
7-Phenol 7-phenol 7-phenol Phenols Dibutylamine III
EC+EC
as above as above Range 0 36 ND*-0.10 ND - ND ND - 0.03 ND - 0.11 0.11 - 0.36 10
Avg. 28 0.02 ND 0.01 0.03 0.22 12,
13
as above EC+WP
Range 0 36 ND - 0.11 ND - ND ND - 0.01 ND - 0.01 0.04 - 0.2
Avg. 28 0.04 ND ND 0.04 0.11
Table 3e Residues of carbosulfan and its metabolites in cereal grains, forage and fodder resulting from
supervised field trials
Application Residues, mg/kg
Country,
year, Rate, Interval, No. of 3-Hydroxy-
crop No. kg a.i./ha Days Samples Carbosulfan Carbofuran carbofuran Ref.
France, 1 0.5 - 1.5 89-193 16 <0.05 <0.05 <0.05 VII-3
1978-79, 5G
grain (mature) formulation
plant (whole) 90-120 32 <0.05 <0.05 - 0.1* <0.05 - 0.12*
* Only value >0.05 mg/kg 90 days post-treatment.
Table 3e (2)
Application Residues, mg/kg
Country,
year, Rate, Interval, No. of 3-OH- 3-Keto- Total
crop No. kg a.i./ha Days Samples Carbosulfan Carbofuran carbofuran carbofuran carbamates Ref.
USA, 1 3.4 (in-
1981, furrow
field corn at-plant)
grain 4 EC 114-170 11 <0.01 <0.02 <0.02 <0.02 <0.07 V-5
formulation
fodder 114-170 11 <0.01 <0.02 <0.01 <0.05 <0.18
[<0.02-0.75] [<0.02-0.25] [<0.02-1.03]
silage 86-131 11 <0.01 <0.2 <0.2 <0.02 <0.02
[<0.02-0.03] [<0.02-1.6] [<0.02-1.6]
phenolic residues
DBA
3-Keto 3-Hydroxy
Crop Part 7-Phenol 7-Phenol 7-Phenol Total Ref.
as above 1 as above 86-131 11 Silage
Range <0.01-0.56 <0.01-1.30 <0.01-1.69 <0.01-3.55 <0.01-0.03 V-
Average 0.05±0.2 <0.11±0.03 0.14±0.4 0.2 2,
3,
114-170 11 Grain 4
Range <0.01 <0.01 <0.01 <0.01 <0.01
Average <0.01 <0.01 <0.01 <0.01 <0.01
3,
114-170 11 Stover
Range <0.01-0.26 <0.01-0.57 <0.01-1.03 <0.01-1.66 <0.01-0.11
Average 0.03±0.06 0.09±0.2 0.16+0.3 0.28±0.5 <0.02 3,
* Average of duplicate determinations
Table 3e (3)
Application Residues, mg/kg
Country,
year, Rate, Interval, No. of 3-OH-
crop No. kg a.i./ha Days Samples Carbosulfan Carbofuran carbofuran Ref.
Brazil, 1 0.23-0.30 101 4 <0.02 <0.02 <0.02 III-21
1982, kg a.i./ha
rice grain (0.75-1 kg
a.i./100 kg
seed)
25 STD
formulation
Greece, Analytical results available, but no sample history provided
1983, V-1
grain
Brazil, 1 625-875g 115 3 <0.02 <0.02 <0.02 III a-32
1983, a.i./100 kg (in
wheat seed=0.75- dupl.)
1 kg a.i./ha
25 STD
formulation
Table 3e (4)
Application Residues, mg/kg
Country,
year, Rate, Interval, No. of 3-OH- Total
crop No. kg a.i./ha Days Samples Carbosulfan Carbofuran carbofuran carbamates Ref.
USA (10 trials, 4 1X 2.2 30-39 III-15
7 states), 10G at plant
1981, + 3X 0.56
sorghum foliar 4EC
stalk 10* [<0.1-1.13] [<0.1-0.-65] [(0.05)-0.85] [0.12-2.27]
0.25 Av. 0.16 Av. 0.43 Av. 0.84 Av.
±0.29 ±0.18 ±0.27 ±0.52
grain 10* [<0.02-0.14] [<0.02-0.29] [(0.02)-0.35] [(0.02)-0.56]
(0.04) Av. 0.05 Av. 0.10 Av. 0.19 Av.
±0.05 ±0.06 ±0.09 ±0.17
Phenolic residues
3-Keto- 3-Hydroxy-
7-Phenol 7-phenol 7-phenol Total DBA
stalk 10* [0.02-2.5] [0.14-0.74] [0.08-0.84] [0.42-4.1] [0.16-1.8] III-14
1.0±0.6 0.44±0.2 0.34±0.2 1.8±1.0 0.8±0.49 16,17
grain 10* [0.08-0.61] [0.06-0.46] [0.02-0.48] [0.24-1.6] [0.19-1.1]
0.19±0.1 0.14±0.1 0.16±0.1 0.49±0.3 0.48±0.28
* In duplicate
Table 3f. Residues of carbosulfan in grass and clover resulting from supervised residues trials
Application Residues, mg/kg
Country,
year, Rate, Interval, No. of 3-Keto- 3-Hydroxy- Total
crop kg a.i./ha Days Samples Carbosulfan Carbofuran carbofuran carbofuran carbamates Ref.
USA (32 Ground or
trials), aerial
1980-81, spray
grass &
clover
green grass 0.28 7 6 0.46[0.07-1.1] 0.67[<0.03-1.8] 0.04[<0.03-0.11] 10.6010.08-1.2] 1.3[0.04-4.4] III-
0.56 14 10 0.55[0.04-1.5] 0.37[<0.03-2.1] 0.03[<0.03-0.20] 1.7[<0.03-2.4] 1.1[0.04-4.4] A
29
green clover 0.28 7 7 0.39[0.04-1.2] 0.47[0.09-1.8] 0.13[<0.03-0.44] 0.87[0.41-1.4] 1.5[0.71-3.4]
0.56 14 10 0.22[<0.02-0.54] 0.44[0.04-1.8] 0.6[<0.03-0.34] 1.2[<0.03-4.1] 1.7[0.08-5.1]
grass hay 0.28 7 6 1.1[0.16-2.4] 1.2[0.24-6.0] 0.07[<0.05-0.25] 1.2[0.26-2.0] 3.0[0.50-8.2]
0.56 14 10 0.77[<0.05-3.9] 1.7[<0.05-12.2] 0.05[<0.05-0.35] [1.6[<0.1-7.2] 3.6[ND-19.8]
clover hay 0.28 7 7 0.46[0.08-1.1] 1.5[0.10-3.5] 0.23[<0.05-1.1] 2.0[<0.1-5.1] 3.7[0.10-8.8]
0.56 14 11 0.31[0.06-0.71] 1.1[<0.05-3.6] 0.19[<0.05-1.0] 6.3[0.22-14.6] 7.7[0.30-17.1]
Table 3f. (continued)
Phenolic residues
Total
3-Keto 3-Hydroxy- phenolic
7-Phenol 7-phenol 7-phenol metabolites DBA
green grass 0.28 7 0.40 [ND**-1.51] 0.15[ND-0.36] 0.45[ND-1.64] 1.00[0.07-2.41] 1.6[0.6-3.8] III-
0.56 14 0.41 [ND-2.69] 0.16[ND-0.47] 0.35[ND-1.66] 0.91[0.04-4.82] 1.1[0.01-2.4] A
22,
green clover 0.28 7 0.28[0.09-0.60] 0.26[0.08-0.45] 0.06[ND-0.16] 0.60[0.18-1.03] 1.7[0.6-3.4] 25,
0.56 14 0.38[0.07-0.99] 0.44[0.12-0.96] 0.12[ND-0.31] 0.94[0.25-2.12] 2.0[0.6-4.9] 26
grass hay 0.28 7 0.86[0.12-1.78] 0.34[0.09-1.18] 1.20[ND-5.88] 2.39[0.61-8.06] 2.9[0.2-4.7]
0.56 14 0.70 [ND-3.36] 0.32[ND-1.31] 0.64[ND-2.89] 1.67[0.04-6.70] 1.7[<0.01-3.6]
clover hay 0.28 7 1.08[0.06-2.62] 0.94[0.11-2.17] 0.45[ND-0.89] 2.47[0.30-5.43] 5.3[<0.01-12.7]
0.56 14 1.38[0.06-3.86] 1.56[ND-03.60] 1.177[ND-1.95] 3.67[0.08-8.97] 7.3[<0.05-21]
* All single applications of 4EC formulation
** ND = not detectable = <0.01 mg/kg green; <0.02 mg/kg hay.
Table 3f (2)
Residues, mg/kg Ref. III-A
30
Total
Country, Application cholinesterase
year, rate, Interval, 3-Keto- 3-Hydroxy- inhibiting No.of
crop kg a.i./ha Days Carbosulfan Carbofuran carbofuran carbofuran metabolites*** Samples
USA (9 states 0.84
15 trials), (ground
green grass or air) 21 0.28[ND**-1.0] 0.25[ND-1.2] 0.50 [0.06-0.92] 0.04 [ND-0.13] 0.78 [0.06-1.9] 7
green clover 21 0.29[ND-1.9] 0.34[ND-2.4] 1.2 [ND-2.9] 0.05 [ND-0.17] 1.6 [ND-4.7] 9
grass hay 21 0.43[ND-2.0] 0.38[ND-1.3] 0.94 [0.14-1.9] 0.05 [ND-0.23] 1.4 [0.14-3.4] 7
clover hay 21 0.43[ND-3.2] 0.57[ND-3.5] 2.8 [0.14-6.5] 0.10 [ND-0.32] 3.5 [0.24-7.6] 9
Table 3f (2) (continued)
Phenolic residues
3-hydroxy- DBA
Crop 7-phenol 3-keto-7-phenol 7-phenol Total phenols Ref.
Green grass 0.29[0.06-0.52] 0.26[0.10-0.69] 0.26[ND**-0.52] 0.82[0.59-0.17] 1.3[ND-2.4] III-A
23,
Green clover 0.28[0.02-0.85] 0.39[ND-1.14] 0.25[ND-1.40] 0.91[0.02-3.07] 1.4[0.4-2.9] 24,
Grass hay 0.50-[0.21-1.15] 0.76[0.16-2.42] 1.04[0.18-2.39] 2.30[0.79-5.19] 2.4[0.5-4] 27
Clover hay 0.82[0.05-2.06] 0.96[0.03-1.86] 0.43[ND-1.01] 2.21[0.05-3.97] 3[0.8-6.2]
* All single applications of 4EC formulation.
** ND = non-detectable: <0.03 mg/kg carbamates and 0.01 mg/kg phenols in green; <0.05 mg/kg carbamates and 0.02
mg/kg phenols in hay; <0.1 mg/kg DBA in all.
*** Max. is total for any one study.
Table 3f (3)
Country, Application Residues, mg/kg
year, rate,* No. of Interval,
crop kg a. i ./ha Samples** Days Carbosulfan Carbofuran Ref.
USA,
1981,
Clover 0.56
seeds 3 0 1.8 [0.51-3.2] 0.07[0.03-0.17] III-A
3 3 0.72 [0.18-1.7] 0.22[ND-0.66] 28
3 7 0.17 [ND-0.40] 0.11[ND-0.23]
3 14 0.26 [0.04-0.74] 0.20[ND-0.55]
3 21 0.16 [ND-0.30] 0.16[ND-0.37]
2 28 0.12[0.04-0.24] 0.16[0.09-0.23]
stems 3 0 28.3 [8.4-63.6] 1.6 [0.77-3.4]
3 3 14.1 [2.0-33.6] 1.5 [0.38-3.8]
3 7 12.1 [0.34-35.4] 2.0 [0.09-5.1]
3 14 4.3 [0.75-7.1] 1.5 [0.21-2.7]
3 21 2.1 [0.45-5.8] 0.91 [0.11-1.5]
2 28 3.6 [0.87-6.6] 2.0 [0.35-3.9]
* Single application of 4EC formulation.
** Two or more analyses on each sample.
ND = not detected = <0.03 mg/kg for carbosulfan and <0.02 mg/kg for carbofuran.
Table 3g. Residues of carbosulfan and metabolites in alfalfa resulting from supervised trials
Residues, mg/kg*** Ref. II-13
Country, Application
year, rate, No. of Interval, 3-Keto- 3-Hydroxy- Total
crop kg a.i./ha Samples days Carbosulfan Carbofuran carbofuran carbofuran carbamates
USA (10 states
15 trials) ,
1980-81,
Alfalfa
green 0.28 (ground) 11 7 0.43 0.11 0.02 1.5 2.1
[0.40-1.2] [<0.03-0.25] [<0.05-0.18] [0.29-3.3] [0.47-4.4]
0.56 (ground 16 14-15 00.25 0.09 0.02 2.9 3.2
or air) [<0.02-0.87] [<0.03-0.22] [<0.05-0.15] [0.55-6.2] [0.65-7.3]
hay 0.28 (ground) 11 7 0.62 0.57 0.05 4.8 6.0
[0.10-2.6] [<0.05-2.1] [<0.05-0.35] [1.5-9.8] [1.7-12.8]
0.56 (ground 16 14-15 0.39 0.43 0.05 8.6 9.4
or air) [<0.05-1.6] [<0.05-1.2] [<0.05-0.34] [0.88-23.0] [1.2-25.5]
Table 3g. (continued)
Phenolic residues
3-Keto- 3-hydroxy-
7-Phenol 7-phenol 7-phenol Total DBA Ref.
as above 0.28 7 0.13 0.34 0.22 0.70 1.8 II-2,
green [0.02-0.28] [0.10-0.65] [0.03-0.56] [0.15-1.3] [<1-3.1] 4,8,9
0.56 14 0.25 0.62 0.50 1.40 3
[0.06-0.68] [0.17-1.30] [0.08-2.10] [0.31-4.10] [<1-8.4]
as above 0.28 7 0.52 1.20 1.30 3.10 3.9
hay [0.08-1.30] [0.45-3.20] [0.09-4.10] [0.66-8.50] [<3.7.1]
0.56 14 0.82 1.90 2.2 5.00 6.2
[0.11-2.30] [0.22-4.40] [0.25-5.70] [0.77-11.00] [<3.14]
* All single applications of 4EC formulation.
** Most samples in duplicate
*** <= below limit of detection
Table 3g (2)
Residues, mg/kg*
Country, Application
year rate, Interval, 3-Keto- 3-Hydroxy- Total Ref
crop kg a.i./ha days Carbosulfan Carbofuran carbofuran carbamates II-2
USA (8 trials),
1979,
Alfalfa 0.56
1 application
green at each of 3 0 26.0 [13.9-62.1] 4.5 [1.9-9.4] 3.0 [0.73-8.3] 33.5 [16.9-73.0]
cuttings 4EC 7 1.1 [0.12-4.3] 0.33 [0.07-0.99] 4.5 [0.89-9.6] 6.0 [1.4-10.8]
formulation 14 0.32 [0<02-2.5] 0.20 [<0.03-1.4] 3.0 [0.48-8.1] 3.6 [0.58-9.6]
hay 0 48.2 [0.09-141] 8.5 [0.66-34.0] 6.9 [0.79-21.0] 63.6 [4.9-185]
7 2.1 [<0.05-11.9] 1.1 [<0.05-6.1] 10.5 [0.19-59.7] 13.7 [0.70-64.1]
14 0.46 [0.05-2.6] 0.46 [0.05-1.9] 8.1 [0.88-22.8] 9.1 [1.1-25.3]
Phenolic residues, mean and [range]
3-Hydroxy- Ref.
7-Phenol 3-Keto-7-phenol 7-phenol Total II-1
green 0 1.0 [0.54-1.3] 0.08 [0.06-0.12] 0.08 [0.05-0.12] 1.2 [0.68-1.5]
7 0.43 [0.24-0.68] 1.1 [0.70-1.4] 0.70 [0.48-0.85] 2.2 [1.4-2.7]
14 0.24 [0.04-0.85] 0.78 [0.10-1.7] 0.40 [0.04-1.3] 1.4 [0.18-4.2]
hay 0 2.5 [1.3-4.0] 0.61 [0.11-1.7] 0.48 [0.12-1.4] 3.6 [1.5-7.1]
7 1.0 [0.57-1.7] 2.4 [1.8-3.7] 1.6 [1.0-2.3] 5.0 [3.4-7.7]
14 0.59 [0.09-1.6] 1.6 [0.14-3.4] 0.97 [0.09-2.1] 3.2 [0.32-6.1]
* <= below limit of detection.
Table 3g (3)
Residues, mg/kg**
Total
Country, Application cholinesterase
year, rate, Interval, 3-Keto- 3-Hydroxy- inhibiting
crop kg a.i./ha days Carbosulfan Carbofuran carbofuran carbofuran metabolites DBA Ref.
USA (10 states
11 trials) ,
1981-82,
Alfalfa 0.84 21 0.08 0.05 0.02 1.7 1.8 1.6 II-5,
green (ground or [<0.03-0.44] [<0.03-0.23] [<0.03-0.28] [<0.03-5.1] [0.14-5.3] [ND-5.2] 11,
air) 14
hay 21 0.12 0.12 0.05 3.5 3.7 3.5
[<0.05-1.1] [<0.05-0.69] [<0.05-0.54] [0.27-16.6] [0.27-17.8] [0.04-15.1]
Table 3g (3) (continued)
Total
cholinesterase
3-Hydroxy- 3-Keto- inhibiting
Cutting Carbosulfan Carbofuran carbofuran carbofuran metabolites Ref.
USA (8 states), 2.1
1982-83, (at plant)
Alfalfa 1 <0.03 0.05 1.3 0.11 1.4 II-15
Spring [<0.03-0.29] [<0.05-8.1] [<0.05-1.1] [ND-8.8]
green hay 58-196 2 <0.03 <0.03 0.09 0.05 0.09
[<0.05-0.62] [ND-0.62]
1 <0.03 0.06 2.1 0.03 2.2
[<0.03-0.39] [<0.05-11.7] [<0.05-0.21] [ND-12.1]
2 <0.03 0.02 0.27 <0.05 0.29
[<0.03-0.14] [<0.05-1.9] [ND-1.9]
Fall 161- 1 <0.05 <0.05 0.03 0.01 0.05
green hay 346 [<0.05-0.14] [<0.05-0.06] [ND-0.20]
2 <0.05 <0.05 <0.05 <0.05 ND
1 <0.05 0.02 0.22 <0.05 0.24
[<0.05-0.08] [<0.05-0.47] [ND-0.55]
2 <0.05 <0.05 <0.05 <0.05 ND
* All single applications of 4EC formulation.
** <= below limit of detection.
Table 3h. Residues of carbosulfan and metabolites in hops and beer resulting from supervised trials
Residues, mg/kg
Country,
year, No. of Interval, 3-OH-
crop Application Samples days Carbosulfan Carbofuran carbofuran Ref.
W. Germany, 6 x 9.75
1981-82, kg a.i ./ha, 11 0 8.1 2.6 1.5 VIII-4
hops 25 EC [0.5-19.4] [0.9-6.2] [0.5-19]
dry formulation
11 7 1.7 0.4 10
[0.16-3.4] [0.05-0.9] [0.24-21]
11 14 0.9 0.4 10
[0.09-2] [<0.05-1.6] [0.36-22]
11 21 1.6 0.3 6
[0.2-3.4] [0.09-0.9] [0.7-11]
11 28 0.6 0.08 3.7
[0.07-2.1] [<0.05-0.24] [0.06-8]
green 5 0 2.6 0.7 1.1
[1.2-6.4] [0.6-1.5] [0.7-3]
5 7 0.8 0.4 1.5
[0.2-3] [<0.05-1.2] [0.3-2.3]
5 14 0.2 0.1 1.2
[0.1-3] [<0.05-0.25] [0.08-2.1]
5 21 0.07 0.07 1.2
[<0.05-0.1] [<0.05-0.13] [0.6-2.8]
Table 3h. (continued)
Residues, mg/kg
Country,
year, No. of Interval, 3-OH-
crop Application Samples days Carbosulfan Carbofuran carbofuran Ref.
5 28 0.08 0.05 1.1
[<0.05-0.2] [<0.05-0.06] [0.7-2.5]
W. Germany, as above
1982,
Spent hops 2 21 [<0.05] [<0.05] [<0.05]
beer 4 21 [<0.05] [<0.05] [<0.05]
Table 3i. Residues of carbosulfan and metabolites in rapeseed resulting from supervised trials
Residues, mg/kg
Country,
year, No. of Interval, 3-OH-
crop Application Samples days Carbosulfan Carbofuran carbofuran Ref.
France,
1979,
rapeseed 1 x 0.45-0.9 8 287-304 <0.05 <0.05 <0.05 VI-2,
(grain) (in furrow) VIII-7
5G formulation
Table 3 Footnotes and References
1 No. of samples is in parenthesis after residue value if not in a separate column
2 Two week intervals;
3 maturity (160 days or more)
4 3 samples
5 10 samples
6 Corrected for recovery
7 Square brackets indicate range throughout Table 3, usually accompanied with mean value
immediately above, below or to the side
8 Residue values in parentheses are estimates, above the limit of detection, but below the
limit of determination
9 Total maximum residue from an individual sample within a study
10 Residues of all three compounds were each <0.05 mg/kg in pulp. Values for fruit and peel are
duplicates at each interval
References: See Table 3 references in reference section.
No data were available for the more leafy members of this group,
so a group limit would not be appropriate.
Legume Vegetables
Only minimal data were available (on dry beans) from one country
(Table 3b). Total carbamate residues were <0.06 mg/kg, but results
were too few to support a limit on beans, even if approved use
information were available.
Citrus Fruit
Data on more than 25 supervised trials were available to the
meeting, but there was no information on nationally approved uses in
either of the two countries in which the trials were conducted
(Table 3c). Most of the data were from the U.S.A. where uses on citrus
are proposed, but as yet unregistered. The application rates and
number of applications in the trials are consistent with those
permitted for experimental purposes only or in one case with the
"suggested" 11g a.i./l water. No safety interval was available.
In most trials samples were analyzed for carbosulfan, carbofuran,
3-hydroxycarbofuran, 3-ketocarbofuran, total carbamates, individual or
total phenolics and dibutylamine (DBA). In general levels of
individual and total carbamates were relatively constant over the 0-28
days-after-last-treatment intervals for any one group of similar
trials. In some trials on grapefruit however, the proportion of
ketocarbofuran increased during the 28-day trial from about 8% to 20%
of the total carbamate. This appears to be typical of the proportion
of 3-ketocarbofuran in citrus relative to the total carbamate residue.
The highest residues found in any of the trials on day 0 and on day 28
respectively were carbosulfan 1.7 and 0.46 mg/kg; carbofuran 0.63 and
1.51 mg/kg; 3-hydroxycarbofuran 0.83 and 0.46 mg/kg; 3-ketocarbofuran
0.1 and 0.27 mg/kg; and total carbamates 2.3 and 2.1 mg/kg. In
general, except on the day of last application when carbosulfan was
frequently higher, carbofuran and 3-hydroxycarbofuran were the
predominant carbamate residues and frequently at similar levels.
Figure 1 illustrates a typical carbamate residue profile in citrus and
is derived from Table 3c (Ref. 1-19; average residues from five
applications).
As in the case of the carbamates, average phenolic and DBA
residues were relatively constant from 0 to 28 days after the last
treatment. The maximum total phenolic and DBA residues found in any
trial were 0.55 and 1.8 mg/kg respectively.
Table 15 illustrates the distribution of carbamate and phenolic
residues in peel, edible fruit and whole mature oranges. Residues are
shown to be almost entirely in the peel. Similar results were observed
for lemons (FMC, 1984, 1-10) and grapefruit (FMC, 1984, I-9), although
up to 8% of the average phenolic residues in grapefruit were in the
edible portion. Most samples were stored at -18°C although
harvest-to-analysis intervals were not provided. Storage trials (see
"Fate of Residues-In Storage") showed no carbosulfan or carbofuran
losses after one year storage of citrus at -18°C.
Pome Fruit
No pome fruit residue data were available from the one European
and two Asian countries where EC and WP formulations respectively are
approved for use (Table 1). Pre-harvest intervals were not provided
even for these countries and information on application rates,
although summarized in Table 1, was received too late for
consideration. Except in one study, "suggested" application rates of
50-75g a.i./1001 water for deciduous fruit could not be compared with
the rates used in the trials. Residue data were available on apples
from two European countries whose approved uses were not known, and on
apples and pears from the U.S.A. where uses are not yet registered.
Data are summarized in Table 3d.
Applications were with EC and/or WP formulations which were
applied by ground or aerially. The highest residues in any trial at 0
and (28) days after the last application were: carbosulfan 2.5 mg/kg
(1.6 mg/kg), carbofuran 0.5 (1.1) mg/kg, 3-hydroxycarbofuran 0.34
(0.8) mg/kg, and total carbamates 3.3 (2.9) mg/kg. In trials in one
country from which no O-day data were available, maximum residues even
after 10 days were 2.3 mg/kg carbosulfan, 0.6 mg/kg carbofuran and
0.3 mg/kg 3-hydroxycarbofuran. When included in the analyses,
3-ketocarbofuran was not detected (<0.02 mg/kg). In general
carbosulfan was the major residue over a 28-day interval followed in
order by carbofuran and 3-hydroxycarbofuran.
Where compared, residues of total carbamates were similar for WP
and EC applications. The aerial applications indicate that carbamate
residues increase with the number of applications and most of the
studies indicate that they are persistent and fairly constant up to 28
days after the last application.
The highest total phenolic residue measured was 0.24 mg/kg. With
average total phenolic residues of 0.12, 0.07 and 0.09 mg/kg at 0, 14,
and 28 days respectively after the last application (FMC, 1984,
III-1), phenolics were shown to be fairly constant from 0-28 days.
Where compared, average individual and total phenolic residues were
similar from WP and EC formulations.
The highest DBA residue in any trial was 0.52 mg/kg and average
DBA residues were relatively constant from 0-28 days after the last
application. In one set of similar trials average DBA residues
resulting from EC application were twice those from WP over the 28-day
period.
Harvest-to-analysis storage conditions were not provided in many
cases. Storage was at -18°C in the U.S. trials, but intervals were not
stated. The U.K. samples were stored at ±20°C (5-29°C before shipment
to the laboratory). No information was provided for the Italian
trials. No storage stability data were provided.
Cereal Grains
Residue data were available from European, North American or
South American countries on corn, rice, sorghum and wheat (Table 3e).
Information on nationally approved application rates was received too
late for consideration. No information was provided on safety
intervals.
Maize. Data were available from one European country whose approved
uses were provided too late for consideration. Data were also
available from a North American country where the use is not yet
registered, although information on uses permitted in experimental
programmes only was provided. In the European trials individual
residues of carbosulfan, carbofuran and 3-hydroxy-carbofuran in mature
grain from in-furrow 5G applications at 0.5-1.5 kg a.i./ha were
<0.05 mg/kg (limit of determination). In whole plants, residues of
each were <0.12 mg/kg. The 1.5 kg a.i./ha furrow rate is twice the
maximum "suggested" granular rate.
In the North American studies at-plant in-furrow EC applications
were at what appears to be three times the experimental permit rate or
suggested rate. Residues in grain were less than the limits of
detection for carbosulfan, carbofuran, 3-hydroxycarbofuran and
3-ketocarbofuran and hence <0.07 mg/kg for total carbamates.
Carbosulfan residues were less than the 0.01 mg/kg limit of detection
in grain, fodder and silage. 3-hydroxycarbofuran was the predominant
residue in fodder and silage. The maximum total carbamate residues
were 0.03 mg/kg and 1.6 mg/kg in fodder and silage respectively.
Maximum total phenolic residues were <0.01, 3.5 and 1.7 mg/kg in
grain, silage and stover respectively. Corresponding maximum DBA
residues were <0.01, 0.03 and 0.11 mg/kg.
Rice. Residue data were available from one European country and one
South American country, although no information on uses was available
for either. Carbosulfan is registered for rice in several countries,
but none in proximity to those from which data were available. The
limited data show individual residues less than the 0.02 mg/kg limit
of detection for carbosulfan, carbofuran and 3-hydroxycarbofuran
(<0.06 mg/kg total).
Application rates could not be compared to the "suggested"
2.5-3.5 g a.i./box of seed (granular); 0.15-0.3g a.i. granular/10 sq.m
seed bed; 0.75-1 kg a.i./ha granular broadcast or 0.2-0.5 kg a.i./ha
EC foliar treatments.
Wheat. Limited data on residues (<0.02 mg/kg each of carbosulfan,
carbofuran and 3-hydroxycarbofuran) but none on use were available
from one country. A 25EC formulation is permitted in one country not
in close proximity.
Sorghum. Data were available from one country in which carbosulfan
is not yet registered. Other use information was available from
European countries where 5G in-furrow applications are permitted, but
not in time for consideration. In the trials for which data were
available, application rates reflected those allowed for experimental
purposes only, except that an at-plant 10G application was also made
in addition to the three foliar EC applications. Maximum residues in
grain 30-39 days after the last application were: carbosulfan 0.14,
carbofuran 0.29, 3-hydroxycarbofuran 0.35 and total carbamates (for
any one sample) 0.56 mg/kg. In stalks the corresponding maximum
residues were 1.13, 0.65, 0.85 and 2.27 mg/kg. Maximum residues of
total phenolics were 4.1 and 1.6 mg/kg for stalks and grain
respectively, and of DBA 1.8 and 1.1 mg/kg respectively.
Information was minimal on harvest-to-analysis storage conditions
for cereals. In the French trials, maize samples were stored up to 9
months at ±20°C. U.S. and Brazilian samples of field corn, rice and
wheat were stored at -18°C and sorghum samples at -20°C but no storage
periods were provided. Storage stability data were available only for
corn forage (see "Fate of Residues-In Storage") where carbosulfan
decreased by 50% and total residues by 30% within one year during cold
storage.
Grass Fodder
Extensive residue data on grass (green and hay) were available
from one country (Table 3f), but no information on approved uses (not
even "suggested" uses). Seven to 21 days after single, ground or
aerial applications of 4EC at 0.28, 0.56 or 0.84 kg a.i./ha to grass,
maximum residues in green grass and (hay) were: carbosulfan 1.5
(3.9) mg/kg, carbofuran 2.1 (12.2) mg/kg, 3-hydroxycarbofuran 2.4
(7.2) mg/kg, 3-ketocarbofuran 0.92 (1.9) mg/kg, total carbamates 4.4
(19.8) mg/kg, total phenolics 4.8 (8.1) mg/kg and DBA 3.8 (4.7) mg/kg.
Legume Animal Feeds
Data on residues in alfalfa and clover from one country, but no
information on nationally approved or even "suggested" uses, were
available.
Alfalfa. Residue data were available from 34 trials with
0.28-0.84 kg a.i./ha EC applications by ground or air and from a
single at-plant EC application on green alfalfa and hay (Table 3g).
Only experimental use information was available; the trials uses were
generally consistent with experimental permits. Data for hay were not
corrected for moisture which varied from 4-52%, but averaged
approximately 23%.
Maximum residues 0-21 days after the last application over all
the foliar treatments in green alfalfa and (hay) were: carbosulfan 62
(141) mg/kg, carbofuran 9.4 (34) mg/kg, 3-hydroxycarbofuran 9.6
(59.7) mg/kg, 3-ketocarbofuran (not measured in all the trials)
0.28 (0.54) mg/kg and total carbamates 73 (185) mg/kg. Highest
residues generally occurred on the first day and total carbamates
decreased to about one-tenth of the initial level by 14 days.
In general air and ground applications resulted in similar
residues especially on green alfalfa. Residues of 3-ketocarbofuran
were generally about 1-5% of the total carbamate residue. Data
provided to the meeting clearly show that there was no increase in
carbamate residue levels in second and third cuttings when there was
on application per cutting.
Maximum total phenolic residues from foliar applications at 0-21
days were 4.2 and 11 mg/kg in green alfalfa and hay respectively.
Average phenolic residues were similar from ground or air applications
after 14 days and the data provided (Ref. II-1 Table 3g) show no
increase in average phenolic residues 14 days after 2nd and 3rd
cuttings. However, 0- and 7-day samples from 2nd and 3rd cuttings were
not analyzed so no conclusion can be drawn on residue increases at
these intervals.
Maximum DBA residues 21 days after foliar ground or aerial
applications were 5.2 and 15.1 mg/kg in green alfalfa and hay
respectively.
In general residues in green alfalfa or hay from at-plant
applications were significantly lower than those from applications
0-21 days before harvest. No residues of carbosulfan per se
remained, but up to 9 and 12 mg/kg carbamate metabolites were present
in spring green alfalfa and hay, respectively, 58-196 days after
treatment.
Clover. Extensive supervised trials data were available from one
country (Table 3f). Maximum residues on green clover and (hay) 7-21
days after ground or aerial EC applications at 0.28-0.84 kg a.i./ha
were: carbosulfan 1.9 (3.2) mg/kg, carbofuran 2.4 (3.6) mg/kg,
3-hydroxycarbofuran 4.1 (14.6) mg/kg, 3-ketocarbofuran 2.9 (6.5) mg/kg
and total carbamates 5.1 (17.1) mg/kg. The 3-ketocarbofuran was
generally <5% of the total carbamate residues. Maximum residues of
carbosulfan and carbofuran were 3.2 and 0.17 mg/kg respectively in
clover seeds and 63.6 and 3.4 mg/kg respectively in the stems on the
day of application. Carbosulfan residues decreased to about one-tenth
of their initial levels by day 28 while carbofuran residues remained
relatively constant.
Maximum total phenolic residues in green clover and hay in any
trial were 3.1 and 9 mg/kg respectively, while maximum DBA residues
were 4.9 and 21 mg/kg.
Harvest-to-analysis storage periods for alfalfa and clover were
not provided, although macerates were stored at -18°C. Field-incurred
residues of carbosulfan in green alfalfa have been shown to be stable
at -18°C (see "Fate of Residues-In Storage").
Oilseed
Limited data on residues in rapeseed resulting from an in-furrow
granular application were available from one country. Residues of
carbosulfan, carbofuran and 3-hydroxycarbofuran were each less than
the 0.05 mg/kg limit of determination (Table 3i). No information on
uses was available.
Unclassified Commodities
Hops. No information on registered or even "suggested" uses was
available. Substantial residue data from one country were available on
green and dry hops, spent hops and beer (Table 3h). Except on the day
of last application, when carbosulfan was the major residue,
3-hydroxycarbofuran was the predominant residue over the 28-day
period. Maximum residues of carbosulfan, carbofuran and
3-hydroxycarbofuran respectively ranged from 19.4, 6.2 and 19 mg/kg in
dry hops on the day of last application to 2.1, 0.24 and 8 mg/kg after
28 days. Corresponding levels on green hops ranged from 6.4, 1.5 and
3 mg/kg on the day of last application to 0.2, 0.06 and 2.5 mg/kg
after 28 days. Residues of each compound were less than the 0.05 mg/kg
limit of determination in spent hops and beer.
FATE OF RESIDUES
General
The fate of carbosulfan has been investigated in plants,
animals, soil, water and light and in storage under a variety of
conditions. In general, carbosulfan, carbofuran, 3-hydroxycarbofuran
and 3-ketocarbofuran are the principle carbamate residues in plants
with relative amounts varying from crop to crop and with time.
Phenolics and dibutylamine contribute an analytically significant part
of the total residue.
The fate in non-food animals is considered under "Biochemical
Aspects". This section describes the fate in goats and poultry.
Residues are rapidly excreted from goats, primarily in the urine.
The principle poultry tissue residues in decreasing order are
3-hydroxycarbofuran, the 3-keto-7-phenol and
3-hydroxy-N-hydroxymethylcarbofuran. No residues of carbosulfan or
carbofuran were detected. Residues in goats and eggs were not
identified.
The names and structures of some carbosulfan-related compounds
are listed in Figure 2.
In animals
Goats. The distribution of radioactive residues from
14C-ring-labelled carbosulfan was studied in the urine, faeces,
blood, milk, expired air and tissues of two lactating goats dosed
twice daily by gelatin capsule for seven days (Huhtanen, 1979; Wu,
1980). The doses were equivalent to average daily dietary carbosulfan
intakes of
4.43 ppm for goat I and 11.4 ppm for goat II. The distribution of
excreted and retained radioactivity is shown in Tables 4 and 5.
Residues in whole milk were directly related to the dose and
became level by day three in both goats. Similar levels were found in
skim milk. Maximum levels in the cream of animals I and II were 25.8
and 69.9 µg/l respectively. Residue levels in blood were also directly
related to the dose and increased throughout the 7-day test period,
ranging from 3.6 to 13.1 µg/l for goat I and from 8.9 to 29.8 µg/l for
goat II.
It can be seen that maximum tissue residues occurred in kidney
and liver with significantly less in fat and muscle.
Two goats were dosed twice daily by capsule for ten days with
14C-carbosulfan labelled in the C-1 position of the dibutylamine
group (Wilkes and Wargo, 1981; Wu 1981). The total daily dose was
10.1 mg/kg, equivalent to approximately 10 ppm in the diet. The
distribution of residues in urine, faeces, blood, expired air, milk
and tissues was determined in goat I which was sacrificed two hours
after the last dose. Milk residues in goat II were monitored and
tissues were analyzed after sacrificing 3.75 days after the last
dosing. This provided data on the loss of residues after cessation of
dosing. Results are shown in Tables 6 and 7.
It is obvious that most of the radioactivity is excreted in the
urine with some excretion in the faeces. Residues in the whole milk of
both animals became steady on day three at 279 and 330 µg/l for goats
I and II respectively. In goat II residues declined to 24.6 µg/l 3.75
days after the last dose.
As in other studies, 14C residues in blood increased throughout
the dosing period and, as in the case of milk, decreased (from 119 to
68.4 mg/l) during the 3.75-day withdrawal period.
FIGURE 2a;V084PR22.BMP
Table 4. Radioactivity excreted by goats dosed with ring-14C
carbosulfan
14C, % of total administered dose
Sample Goat I Goat II
urine 81.5 79.8
faeces 2.3 2.8
milk 0.6 0.6
expired gases 2.1 2.6
Total Recoveries 86.5 85.9
(adjusted)*
* Adjusted to take into account urine losses and contamination
of faecal samples.
Table 5. Radioactivity in tissues, blook and milk of goats dosed
with ring-14C carbosulfan
Total 14C expressed as µg/kg (ppb) carbosulfan
Tissue Goat I Goat II
liver 31.0 111.2
kidney 49.7 118.4
heart 9.9 25.2
back muscle 4.2 16.1
foreleg muscle 7.0 12.3
hind leg muscle 6.2 22.7
omental fat 5.2 6.1
milk (maximum levels) 21.3 (mean 16) 50.8 (mean 43)
blood (at sacrifice) 17.9 33.5
Table 6. Radioactivity excreted by goat dosed with
dibutylamine - 14C carbosulfan
14C excreted (goat I)
Sample % of
% of total dose adjusted dose*
urine 68.79 79.40
faeces 2.28 2.69
milk 1.40(2)** 1.40(2)**
expired gases 0.62 0.62
Total Recovery 73.09 84.10
* Excluding first and final days which did not represent full
24-hour periods.
** Goat II in parenthesis
Table 7. Radioactivity in tissues, blood and milk of goats dosed with
dibutylamine-14C carbosulfan
Total 14 expressed as µg/kg (ppb carbosulfan
Tissue Goat I Goat II
(2 h after last dose) (3 days after last dose)
liver 541.9 341.2
kidney 611.4 149.4
heart 75.9 43.4
back muscle 71.7 29.3
foreleg muscle 77.3 31.9
hind leg muscle 72.1 34.1
omental fat 7.7 27.5
subcutaneous fat 11.6 19.4
milk (maximum level) 312.4 363.0
blood (last day of dosing) 109.2 119
blood (at sacrifice) 109.2 68.4
Also confirming other studies, residues were highest in kidney
and slightly less in liver in the goat killed shortly after the last
dose, whereas 3.75 days after cessation of dosing the residue in the
kidney was less than half that in the liver. Residues in other
non-fatty tissues of goat II declined to about half those in goat I. It
also appears that fat residues increased substantially during the
withdrawal period. This is probably due to cleavage of the fat-soluble
dibutylamine side chain.
Poultry. The fate of carbosulfan in laying hens dosed by capsule
was investigated in three closely interrelated studies (Wilkes et
al., 1981; Markle, 1982a, b). The hens were dosed daily for 14 days
at levels equivalent to 0.5, 1.5 and 5 ppm in the diet (0.05, 0.15 and
0.5 mg/kg body weight) with 14C-ring or 14C-dibutylamine
(DBA)-labelled carbosulfan. Eggs were collected throughout and the
hens slaughtered at 6h. and 7 and 14 days after the last dose. Total
residues were determined by oxidative combustion and identification
was by chromatographic and spectrometric techniques. Dibutylamine was
derivatized with phenyl isocyanate for analysis.
In eggs, residues of both labelled compounds became steady after
7-10 days with those from the highest dose reaching approximately 0.01
and 0.03 mg/kg carbosulfan equivalents in egg whites and yolks
respectively for the ring label and 0.1 and 2 mg/kg respectively for
the DBA label. As evident in Table 8, residues were dose-dependent
with both labels, higher in yolks than whites and higher in yolks and
whites from the DBA label than from the ring label. On cessation of
dosing residues from the ring label decreased to the 0.002 mg/kg limit
of detection after 11 days, whereas residues had decreased only to
0.06 mg/kg (yolk) by 12 days after cessation of the DBA-label feeding.
In tissues from ring-label feeding, residues were less than the
0.002 mg/kg carbosulfan equivalents limit of detection at all three
dose levels after 7 days of dosing. Dose-related residues occurred on
the first day of dose administration and from the high dose level were
0.3 mg/kg in liver and 0.2 mg/kg in other tissues. Seven days after
cessation of dosing residues had decreased to approximately the limit
of detection in all tissues, with depletion fastest from liver and
slowest from fat.
The residue profile in liver and thigh muscle is shown in Table 9
for the high dose level at day 0. It can be seen that the
3-hydroxy-7-phenol, at 16% of the total, is the major residue in
liver, whereas 3-hydroxycarbofuran at 37% of the total is the major
thigh muscle residue. Other metabolites occurred also, but neither
carbosulfan nor carbofuran was found. The residue profile in eggs was
not determined for the ring-label feeding.
Table 8. Maximum residues in eggs following dosing with 14C-ring- or
DBA-labelled carbosulfan
Radioactivity calculated as
carbosulfan, mg/kg
Dietary Ring Label DBA Label
Feeding White Yolk White Yolk
Level (ppm)
0.5 <0.002* <0.002 0.014 0.18
1.5 <0.002 0.007 0.033 0.58
5 0.012 0.031 0.13 2
* Limit of detection.
Table 9. Residues in thigh muscle and liver of chicken, 6h after dosing with
14C-ring-carbosulfan at 5 mg/kg bw.
Fraction Thigh Muscle Liver
% of muscle
residue mg/kg % of liver mg/kg
Extractable residues
Carbosulfan metabolites
Carbosulfan - <0.002 - <0.002
Carbofuran - <0.002 - <0.002
3-OH, N-hydroxymethylcarbofuran 9.3 0.007 2.1 0.004
3-OH-7-phenol 7.1 0.004 16.1 0.021
3-OH-carbofuran 36.9 0.026 1.1 <0.002
3-Keto-7-phenol 6.4 0.003 2.5 0.003
3-Keto-carbofuran 1.7 <0.002 1.7 0.003
7-Phenol - <0.002 3.3 0.004
Minor metabolites 2.1 <0.002 0.5 <0.002
Extractable unknowns
MW > 500 3.0 - 8.3 -
Other 3.6 - 2.4 -
Total % Extractable 70.1 - 37.9 -
Aqueous 14.6* - 44.9* -
Post-extraction solids 1.6 - 18.6* -
Total % recovered 86.3 - 101.4 -
* These fractions were hydrolyzed with 0.25N HCl. Hydrolysis products include
unknowns and ¾2.1% of individual tissue residues, 3-keto carbofuran,
3-keto-7-phenol and 7-phenol.
As in the case of eggs, tissue residues from the DBA label were
significantly higher than from the ring label. From the high DBA label
dosing at day 0 residues in liver were 1.4 mg/kg carbosulfan
equivalent, fat 0.4 mg/kg, gizzard 0.3 mg/kg and heart, skin and
muscle all <0.24 mg/kg. Tissue residues generally decreased over
the test period except in skin where they were relatively constant and
in fat where they apparently increased, especially at the lower dosing
levels. On cessation of dosing residues decreased to <0.1 mg/kg in
all tissues except fat and skin in which they remained constant or
even increased slightly during the 14-day withdrawal period.
The predominant identified 0-day tissue residue from the high
DBA-labelled dose was dibutylamine at 0.12 mg/kg (22.5% of the tissue
total) in muscle and 0.18 mg/kg (36.9% of the total) in liver. The
other residues in these tissues were for the most part unidentified.
In fat only 3.1% of the residue was DBA with another 81.7%
characterized as extractable unknowns. This increased to 99.2% after
14 days.
In eggs only approximately 4% of the residue (after 9-12 days,
yolk and white) was identified as DBA with 86% in the yolks
characterized as extractable unknowns and 72.5% in the whites as
either water-soluble (6.5%) or post-extraction solids (66%). It was
confirmed by GCMS that the 14C label was incorporated into individual
fatty acids, thus identifying a major route for the DBA side-chain
metabolism. The same was found for chicken fat samples.
Feeding studies were conducted with egg-bearing white leghorn
chickens fed daily by capsule for 28 days with non-labelled
carbosulfan and separately with non-labelled dibutylamine equivalent
to dietary levels of 1.5 ppm carbosulfan and 10 ppm dibutylamine. Eggs
were collected periodically throughout the study and liver, fat and
muscle samples taken on days 28, 31 and 35 (Tilka, 1983; Leppert,
1983a). Using analytical methods similar to those used in
carbosulfan metabolism studies, tissue samples were analyzed by
thermionic-nitrogen-phosphorus GLC for carbosulfan, carbofuran,
3-hydroxycarbofuran and 3-ketocarbofuran (the latter after hydrolysis
and ethoxylation). The limits of determination and detection were 0.05
and 0.005 mg/kg for each compound in each tissue. Analytical
recoveries from 0.05-0.1 mg/kg fortifications were >70% for all
compounds in all tissues except 3-hydroxycarbofuran at 65 and 68% in
muscle and fat respectively and 3-ketocarbofuran at 66% in fat. No
residue was detected in any of the tissues at the 0.005 mg/kg limit of
detection. This is consistent with results from the chicken metabolism
studies, with labelled carbosulfan.
The eggs (whole) were analyzed for the same compounds with limits
of determination of 0.02 mg/kg for carbosulfan and carbofuran and
0.01 mg/kg for 3-hydroxycarbofuran and 3-ketocarbofuran. Average
recoveries were 70% for carbosulfan, 65% for carbofuran, 83% for
3-hydroxycarbofuran and 66% for 3-ketocarbofuran, although individual
recoveries were frequently only 50% (except 3-hydroxycarbofuran
>60%). Fortification levels were generally 0.02-0.1 mg/kg. The
analytical procedure for eggs was similar to that for tissues except
that carbosulfan and carbofuran were initially extracted with
acetonitrile instead of ethanol/diethyl ether/hexane. As in the case
of tissues, no residues were detected at the 0.005 mg/kg limit of
detection.
Neither tissue nor egg samples were analyzed for the carbamate
3-hydroxy-N-hydroxymethylcarbofuran which was identified as 9.3% of
the total thigh muscle residue in chicken metabolism studies (Table
8), nor were any samples analyzed for dibutylamine although some hens
were fed a 10 ppm dietary level.
In plants
Apples. The persistence of carbosulfan and its
cholinesterase-inhibiting metabolites on apple leaves after three 1.1
kg a.i./ha foliar sprays of EC and WP formulations was investigated
during re-entry studies (Leppert, 1982). Half-lives of carbosulfan and
carbofuran were 4-5 and 12.5-16 days respectively: the dissipation
followed first order kinetics. Dissipation rates were similar for the
two formulations. Residues of 3-hydroxycarbofuran were approximately
one-hundredth and one-tenth of the carbosulfan and carbofuran residues
respectively at day 1 and were at about the same level (0.03 mg/cm2)
on day 21. Residues of 3-ketocarbofuran were <0.01 mg/kg (limit of
detection) throughout the 21-day study.
Cotton and corn. The fate of carbosulfan was studied in the cotton
plant at 1, 3, 6 and 10 days after painting leaves with an
ethanol:acetone:water solution of 14C-carbosulfan labelled in the
dibutylamine side chain (Nishioka et al.). Surface residues and
organosoluble, unextractable and water-soluble fractions were analyzed
by GLC. Extraction was with buffered methanol containing N-ethylamide
(NEM) as a sulfhydryl scavenger.
The total radioactivity recovered ranged from 88 to 101% of that
applied. Surface residues decreased from 13.6% of the applied a.i. at
day 1 to 3.2% at day 10 (9.5% to 0.6% as carbosulfan). Internal
organosoluble residues accounted for 86-96% of the applied activity,
and by day 10 dibutylamine accounted for approximately 60% of it
(mostly as internal residue). A significant proportion of this was
scavenged with the NEM. Three other major internal organosoluble
metabolites were not identified, but accounted for 9.1, 16.6 and 10.5%
of the applied radioactivity. Carbosulfan in the internal fraction
accounted for <1.1% of that applied.
The absorption, translocation and metabolism of 14C-ring- and
carbonyl-labelled carbosulfan were studied in cotton and corn plants
following both foliage applications and stem injections (Umetsu et
al., 1979). Carbonyl-14C carbosulfan residues remained at the point
of application (up to 9 days) when the carbosulfan was applied near
the tips of corn and cotton leaves, but were translocated to the whole
leaf within 24 hr when it was applied to the base of a cotton leaf.
Most of the radioactivity remained for up to 6 days with little
translocation to opposite leaves. Radioactivity from stem injections
of ring- or carbonyl-labelled carbosulfan in cotton and corn was
rapidly translocated to the plant extremities, but only slightly to
new growth.
In cotton plants after stem injection of 14C-ring or
carbonyl-labelled carbosulfan total organosoluble radioactivity
decreased from approximately 90% of that applied at day 1 to 55% at
day 10, while water-soluble conjugates increased from approximately 9%
to 40%. For both labels by day 10 carbosulfan and carbofuran were the
major residues, at roughly the same levels, together accounting for
approximately 50% of the applied radioactivity. 3-hydroxy-carbofuran
(mostly conjugated) was the next major metabolite with either label,
increasing from approximately 10% of the applied radioactivity at day
1 to 20-30% by day 10. The three compounds therefore accounted for
approximately 70-80% of the injected radioactivity. Other identified
residues were 3-hydroxyphenol <3%, 3-ketocarbofuran <8% and
N-hydroxymethylcarbofuran <5% of the injected carbosulfan.
The same metabolites were found in corn after stem injection of
14C-carbonyl-labelled carbosulfan, although conversion to carbofuran
was more rapid in corn (56% of the applied carbosulfan appeared as
carbofuran at day one) and most of the metabolites remained
unconjugated.
When carbonyl-labelled carbosulfan was painted on cotton leaves,
the distribution of radioactivity after 1 and 10 days respectively was
69 and 15% of that applied in surface residues; 18.9 and 12.5% in
internal extracts and 11 and 66% as water-soluble conjugates. The
surface and internal residues found are shown in Table 10.
Similar results were found with 14C-ring-labelled carbosulfan
except that additional metabolites in the water-soluble conjugate
fraction were the 3-ketophenol (10% of the applied radioactivity), the
phenol (<3%), and the 3-hydroxyphenol (<5%).
Corn metabolism studies were conducted on the basis of in-furrow,
at-plant soil-sprayed applications of either ring-14C or DBA-14C
carbosulfan at an equivalent of 3.3 kg a.i./ha (FMC, 1984, V,(1)).
Plants were grown in tanks in a greenhouse but simulating field
conditions, and harvested at 31, 60, 110 (silage stage) and 136 days
(maturity). Stalks, leaves, husks and grain of mature grain plants
were analyzed. Analysis of free and (after HC1 hydrolysis) conjugated
residues was by HPLC and scintillation counting. The dibutylamine
fraction was reacted with phenyl isocyanate before analysis.
In the ring study the major residues (combined conjugates and
non-conjugates) were as shown in Table 11.
Table 10. Residues from foliar application of 14C-carbonyl
carbosulfan to cotton
% of applied radioactivity
Residue Day 1 Day 2
Surface
Carbosulfan (free) 18.1 1.6
Carbofuran (mostly free) 49.2 12.6
3-hydroxycarbofuran 19.6 62.1
(mostly conjugated)
86.9 90.7
3-ketocarbofuran <2%
N-hydroxymethylcarbofuran <5%
3-hydroxy-N-hydroxymethylcarbofuran <0.7%
Day 1 Day 10
Internal organosoluble
carbofuran 14 7.9
carbosulfan 3.4 1.7
others (each) <1 <1.4
Table 11. Residues in corn from soil treatment with ring-14C-labelled carbosulfan
% of recovered radioactivity
Interval (days)
Residue 31 60 110 136
Stalks
&
Leaves Husks Grain
3-hydroxycarbofuran 24.9 22.3 13.6 12.2 10.3
carbofuran 23.8 16 2.6 1.7 0.2
3-keto-7-phenol 4.8 15.1 11 9.7 6.7
3-ketocarbofuran 3.2 3.1 1.2 2.1 2.9
3-hydroxy-7-phenol 2.2 2.1 6.7 4.7 9.8
7-phenol 0.5 3.2 3.7 2.1 3.1
3-hydroxy-N-hydroxymethylcarbofuran 0.3 0.6 - - -
unidentified (organosoluble)1 18.5 18.5 15.3 16.9 8.6
Total organosoluble 78.2 80.9 55.5 49.4 42.9 6.4
Total 14C expressed as carbosulfan mg/kg 20 6.4 4.4 25.1 1.8 1.1
1 No one compound exceeded 6.5%
Carbosulfan, its keto and hydroxy metabolites and its sulphone
and keto sulphone (also free) were each <0.02%, and were detectable
only at the 31-day interval. Carbofuran and its 3-hydroxy metabolite
were mostly (>60%) unconjugated at 31 days, but conjugated or bound
residues were predominant by the silage stage.
In the study with DBA-labelled carbosulfan total 14C expressed
as carbosulfan ranged from 3.6 mg/kg at 31 days to 1.2 mg/kg at 110
days. Non-conjugated metabolites in corn plants ranged from 40% of the
total radioactivity at 31 days to 19% in mature stalks and leaves.
Dibutylamine was the major residue ranging from 31% at 31 days to 8%
in mature plants with none in the husks or grain.
Carbosulfan and its keto, hydroxy, and sulphone metabolites
occurred only at 31 days with residues of carbosulfan 0.3%,
carbosulfan sulphone 0.4% and 3-ketocarbosulfan sulphone 2% of the
total recovered activity.
At the silage and mature stages DBA was the only residue
identified (9.3 and 7.6% of the recovered radioactivity respectively).
In husks and grain over 90% of the recovered radioactivity was polar
or bound unidentified residue.
Thus, these corn studies indicate that carbofuran, its 3-hydroxy
metabolite and dibutylamine are the predominant identified residues in
corn from soil treatments with only low levels of parent compound and
its sulphur-containing metabolites in immature plants.
Alfalfa. Tank-grown alfalfa was foliarly treated under simulated
field conditions with either ring-14C or DBA-14C labelled carbosulfan
as an emulsifiable concentrate at a rate equivalent to 0.5 kg a.i./ha.
Ring-14C carbofuran was similarly applied for comparison, but a
flowable formulation was used. In each case residues were
characterized, identified and quantified at 7 and 14 days. After an
initial methanol/phosphate buffer extraction, samples were separated
into non-polar and polar fractions for analysis by scintillation
counting or HPLC. Conjugates were hydrolyzed with 0.25 N HC1 and
C-dibutylamine was derivatized with phenyl isocyanate to permit HPLC
analysis (Bixler, 1982).
The 14C-carbofuran study demonstrates that non-conjugated
carbofuran is the major residue at 7 or 14 days, accounting for
approximately 46% of the recovered radioactivity. The next most
abundant is 3-hydroxycarbofuran, approximately 14% at 14 days, mostly
as a conjugate. Combined unidentified conjugates and non-conjugates
accounted for 13.1 and 12.9% of the recovered radioactivity at 7 and
14 days respectively (each compound 44%). Unidentified water-solubles
and unextractables together accounted for another 17%. Total carbamate
residues (conjugated and free) accounted for 60% of the recovered
radioactivity (50% of that applied). Phenols accounted for the rest of
the identified residues.
In the 14C-DBA study, free carbosulfan at 46.8 and 26.3% of the
recovered radioactivity at 7 and 14 days respectively was the major
residue. Dibutylamine at 14.3% and 38% at the same intervals was the
major metabolite, followed by free 3-hydroxycarbosulfan at 1.7 and
1.5% respectively. Other identified non-conjugated carbamate
metabolites were each <1% at both intervals. Conjugated compounds
were not identified. Unidentified non-conjugates were up to 18.7%
(each <6.5%) and unidentified water-solubles and non-extractables up
to 17 and 5% respectively, depending on the interval, with
water-solubles decreasing and non-extractables increasing from 7 to 14
days.
In the 14C-ring study, 72% of the recovered respectively was
identified at 7 days, but only 50.2% at 14 days. Total carbamate
residues (free and conjugated) decreased from approximately 64% of the
recovered 14C at 7 days to 40% at 14 days while phenolics and
unidentified residues increased. The identified residues at 7 and 14
days are listed in Table 12.
Unidentified residues (after 7 and 14 days) were characterized as
combined conjugates and non-conjugates 11 and 22.7%, water-solubles
5.6 and 10.9% and non-extractables 11.2 and 16.2% at 7 and 14 days
with no individual conjugate exceeding 3.1 and 7.5%.
Comparison of the flowable 14C-carbofuran and 14C-ring-labelled
carbosulfan studies indicates that carbosulfan was degraded more
rapidly, possible because there was more penetration by the EC
formulation.
Rice. Tank-grown rice was treated via the soil, under greenhouse
conditions simulating field conditions, with 14C-ring labelled
carbosulfan and carbofuran. Application was at rates equivalent to
1.1 kg a.i./ha carbosulfan and 1.0 kg a.i./ha carbofuran. Grain heads
were also treated with carbosulfan only by syringe at 2 µCi/head 148
days after the soil treatment (Capps, 1980a). In all cases application
was in ethanol solution. Tanks were flooded after ethanol dissipation
and transplanting of 2-week-old plants. Plants from the soil
application were harvested at 11 and 30 days after treatment (15 days
for carbofuran). Grain was sampled 45 days after the grain head
treatment. Combined conjugated and non-conjugated residues in the
plants from the soil treatment and in the grain from the grain head
treatment from carbosulfan applications are shown in Table 13.
From the soil application carbosulfan is evidently rapidly
degraded to carbofuran which is translocated and metabolized.
Carbofuran and its major metabolite 3-hydroxycarbofuran decline with
time while other metabolites, especially phenolics, increase. Even low
levels of the parent compound are taken up in time, although not
detectable initially. As would be expected, conjugated residues
increase with time. Carbamates accounted for 69% of the recovered
radioactivity at 11 days in the plants and 56% in the grain. Of the
recovered grain residues 94.6% were polar non-extractables but
residues were too low for identification.
Table 12. Residues from foliar application of 14C-ring
carbosulfan to alfalfa
Residue % of recovered radioactivity
Major Day 7 Day 14
3-hydroxycarbofuran (conjugated) 19.3 6.1
carbosulfan (free) 14.3 5.9
carbofuran (free) 11.4 8.8
3-hydroxycarbofuran (free) 8.8 9.1
Minor
carbofuran (conjugated) 3.2 1.6
3-keto-7-phenol (conjugated) 3.2 5
3-ketocarbofuran (free) 2.4 2.5
3-hydroxy-7-phenol (free) 2.1 1.2
3-keto-7-phenol (free) 1.6 1.0
3-ketocarbofuran (conjugated) 1.6 1.4
carbosulfan sulphone (free) 1.2 1.6
7-phenol (conjugated) 0.8 4.1
Trace (<1%)
3-keto carbosulfan (free), hydroxycarbosulfan (free) and
3-hydroxy-N-hydroxymethylcarbofuran.
Table. 13. Residues in rice plants and grain from soil and grain head treatment
with 14C carbosulfan
Plants Grain (head
Residue (soil treatment) treatment)
11 days 30 days 45 days
carbofuran 45.3 12 29.1
3-hydroxycarbofuran 20.2 9.4 7.7
3-keto-7-phenol 3.3 7.6 4.3
3-keto-carbofuran 2.1 0.9 2.3
3-hydroxy-7-phenol 1.6 1.7 1.8
7-phenol 1.2 13.6 2.2
desmethyl-carbofuran 1.1 2.6 2.2
3-hydroxy-N-hydroxymethylcarbofuran 0.1 0.6 0.4
carbosulfan 0 0.2 5.7
N-hydroxymethyl-3-ketocarbofuran 0 0 1.9
3-hydroxy-7-phenol - 0 1.8
carbosulfan sulphone - - 1.7
3-hydroxycarbosulfan - - 1.0
others 6.7a 17.2 11b
aqueous 1.7 15.4 2
non-extractable (or bound) 16.5 18.4 44.5c
a none exceeded 2.2%
b none exceeded 3.2%
c 9% carbofuran, 17.8% bound, others <5%
More metabolites were identified in head-treated grain than in
plants from the soil treatment. The major products were similar, but
the proportion of carbosulfan (mostly free) was much higher in the
grain. The major residues in rice plants were shown to be similar at
11 or 15 days whether carbosulfan or carbofuran was used in the soil
treatment.
In whole-plant autoradiography studies (Capps, 1980b) carbosulfan
and carbofuran showed the same movement with residues concentrating in
leaf tips and roots after soil treatment with the 14C-ring-labelled
compounds. When 14C-dibutylamine-labelled carbosulfan was used
however, radioactivity was evenly distributed throughout the leaves.
The major soil degradation products carbofuran and dibutylamine
initially accumulated in young plants. The similarity of distribution
could be accounted for by the initial degradation to carbofuran and
its metabolites. This would be consistent with the study described
above (Capps, 1980a) and would indicate little if any systemic
penetration of rice by carbosulfan per se from soil application.
In another 14C study carbosulfan labelled in the dibutylamine
group was applied to soil in which rice seedlings were grown under
simulated field conditions (greenhouse), or as a foliar application to
rice plants. The soil application rate was the same as in the study
with ring-labelled carbosulfan. Planting and sampling were similar
with the same 11- and 30-day harvest intervals. Separation and/or
analyses were by GLC, HPLC and sintillation counting (Capps, 1980c).
From the soil treatment 76 and 81% of the plant radioactivity was
non-extractable at 11 and 30 days respectively. The non-extractables
were not identified in the 11-day samples but, after hydrolysis,
dibutylamine accounted for 3.3% of the recovered radioactivity at 30
days. At 11 days, of the 24% extractables only carbosulfan and
dibutylamine were identified (0.7 and 2.5% respectively of the total
recovered radioactivity or together 13% in that fraction). From the
foliar treatment, 92% of the recovered radioactivity at 30 days in the
mature grain was unidentified non-extractable residue.
In grain from the foliar treatment, radioactivity was 54%
extractable and 40% non-extractable at 30 days. 15.6% of the
extractable radioactivity recovered from the grain was carbosulfan and
39.6% was dibutylamine. Other carbamates (sulphenylated) and unknowns
each accounted for <2.0%.
Soybean. Potted soybean plants were grown in soil treated with
ring-14C or DBA-14C labelled carbosulfan under greenhouse conditions.
Immature plants were harvested for analysis at 30 and 60 days and
soybeans at maturity. The residues found are shown in Table 14.
Table 14. Residues from treatment of soybeans with 14C carbosulfan
% of recovered radioactivity
Ring label DBA label
30-day 60-day Mature 30-day 60-day
plants plants beans plants plants
carbofuran 27.7 9.7 -
3-hydroxycarbofuran 20.1 8.6 0.5
3-keto-7-phenol 13.8 24.2 4.3
3-hydroxy-7-phenol 5.9 2.2 2.1
7-phenol 3.7 7.3 0.5
3-keto-carbofuran 2.1 1.1 -
3-hydroxy-N-hydroxymethylcarbofuran 0.6 0.3 -
carbosulfan metabolites ND1 ND -
3-ketocarbosulfan sulphone - - - 4
carbosulfan - - - 0.4 0.02
unidentified 7.42 15.42 8.83 9.14 7.74
1 ND = none detected by HPLC
2 Non-conjugated and conjugated, none >3.2%
3 conjugates, none >2.8%
4 non-conjugates, each <3.2%
These data confirm that carbofuran and its 3-hydroxy metabolite
are the major carbamate plant residues from soil application, with
negligible residues of carbosulfan and its metabolites suggesting
little systemic action. Dibutylamine was not detected in this study.
Carbofuran was mostly non-conjugated, whereas the 3-hydroxy metabolite
was more or less equally non-conjugated and conjugated.
In soil
Adsorption and leaching. In adsorption/desorption experiments,
14C-labelled carbosulfan, carbofuran and dibutylamine were compared
with DDT and 2,4-D in four soils ranging from fine sand to sandy clay
loam with pH values between 5 and 7 (Robinson, 1980). Carbosulfan was
found to be more tightly bound in each soil than 2.4-D and carbofuran,
although not as tightly as DDT. Carbofuran was slightly less strongly
bound than 2,4-D in silt or clay loam and fine sand and dibutylamine
more bound than 2,4-D, but significantly less than carbosulfan. These
results were generally confirmed by thin layer investigations,
although carbosulfan was degraded to carbofuran on the silt and clay
loam plates (Robinson, 1981).
The leaching of seven-day-aged carbosulfan residues in fine sand,
sandy loam and silt loam was investigated in soil columns (Reynolds,
1982). Soil radioactivity was shown to be fairly evenly distributed
throughout the bottom portion of the 2.5 × 30 cm columns after eluting
the fortified soil plug into similar untreated soil below.
Approximately 98% of the recovered radioactivity was retained by the
silt loam after elution with 250 ml water, while in fine sandy and
sandy loam 46.7 and 73.8% respectively were eluted, with most of the
remaining radioactivity in the treated soil plugs. There appeared to
be no relation between the extent of elution and soil texture, organic
matter or pH. The propensity for elution was, oddly and perhaps
coincidentally, inversely related to cation exchange capacity.
Carbofuran was shown to be the major residue in aged soil as well
as in eluates, with only low levels of carbosulfan (<0.8% of the
recovered radioactivity) in soil and none in eluates. Low levels
(<0.6% of recovered radio activity) of 3-ketocarbofuran were
detected in eluates and up to 2% of the recovered activity in soil and
eluate was the 7-phenol. Low levels of unidentified extractable
metabolites were also detected in column soil or eluate, but
constituted <2.1% of the recovered activity. This would probably
include a number of carbosulfan or carbofuran metabolites which were
identified in the aged soil before elution, no one of which exceeded
the 1.6% of 7-phenol and 1.4% of carbosulfan sulphone which were among
those identified. These studies confirm earlier results showing low
potential for carbosulfan leaching but substantial degradation to and
elution of its metabolites, primarily carbofuran.
The retention of carbosulfan was confirmed by citrus field
studies in which soil samples were analysed after four applications of
carbosulfan (two at 4.2 kg a.i./ha and two at 1.1 kg a.i./ha, in a
2.5EC formulation) (Leppert, 1983c). The study showed that carbosulfan
remained in the topsoil and/or adhered to sediments. Carbofuran
penetrated 1.2m of sand to an underlying clay layer, although at low
levels.
Dissipation of residues. The dissipation of carbosulfan in soil has
been investigated following applications to an alfalfa field, citrus
groves and an apple orchard. Degradation under aerobic and anaerobic
conditions was also studied.
In the alfalfa study silt loam and clay soils were analysed for
carbosulfan and carbofuran at 0-15 and 15-30 cm depths at various
intervals after three 1.1 kg a.i./ha 4EC applications, (one
application per cutting) (Leppert, 1981a). The highest carbosulfan
residue at any interval, depth or cutting was 0.18 mg/kg after a
second cutting in the 0-15 cm sample on the day of application. The
corresponding carbofuran residue was 0.09 mg/kg. The maximum
carbofuran level at any interval or cutting was 0.12 mg/kg (second
cutting, 0-15 cm depth, 7-day interval). The maximum total of the two
combined in any sample was 0.27 mg/kg. After 30 days carbosulfan was
<0.05 mg/kg in all 0-15 cm samples and carbofuran was <0.06 mg/kg
(only one sample exceeded 0.05 mg/kg). All 15-30 cm samples contained
<0.05 mg/kg carbosulfan and carbofuran except one which contained
0.1 mg/kg carbofuran. There was no evidence of residue accumulation
from one cutting to the next.
Carbosulfan and carbofuran were determined in the sandy soil of
citrus groves after a single treatment with a 4EC formulation at
1.0 kg a.i./ha and after two additional applications at 4.1 kg a.i./ha
followed by a 1.0 kg a.i./ha application (Leppert, 1981b). The highest
carbosulfan residue from the single treatment was 0.34 mg/kg in
0-15 cm soil on day 0 and this had decreased to <0.05 mg/kg (limit of
determination) by 28 days. The maximum carbofuran residue was
0.14 mg/kg after 3 days. Both compounds were <0.01 mg/kg at all
intervals in 15-30 cm soil.
After the last 3 treatments, the highest O-day carbosulfan
residue in 0-15 cm soil was 0.09 mg/kg, lower than after the single
application, but 3-day carbofuran was higher (up to 0.38 mg/kg).
Residues were also higher in 15-30 cm soil with maxima of 0.02 mg/kg
carbosulfan and 0.07 mg/kg carbofuran after 3 days.
Sandy citrus grove soil was also analysed for carbosulfan and
carbofuran after a single 15G application at 11 kg a.i./ha (Leppert,
1981c). As might be expected because of the higher application rate
and the type of formulation, and possibly because of the lower average
temperatures and significantly less precipitation, residues were
higher than in the study described above. Maximum carbosulfan and
carbofuran residues were 21.6 mg/kg (0-day) and 4.8 mg/kg (3 days)
respectively in 0-15 cm soil samples, with a maximum total in any one
sample of 23 mg/kg. Maximum residues after 56 days were carbosulfan
0.46, carbofuran 0.92 and total 1.36 mg/kg. Residues were lower in
15-30 cm soil samples. To minimize storage decomposition (see "In
storage") all samples were analysed within three weeks of receipt as
compared to 3-166 days (60 days for three applications) in the alfalfa
study. This too could have contributed to higher residues.
Carbosulfan and carbofuran residues were also determined in soil
from an apple orchard after foliar treatment 2.2 kg a.i./ha (4EC) when
dormant, followed by three 25WP foliar applications during the growing
season (Leppert, 1983b). No carbosulfan was carried over to the fourth
application from the three earlier applications. In 0-15 cm soil
samples maximum average carbosulfan residues from duplicate
determinations decreased from 0.12 mg/kg at day 0 to 0.04 mg/kg
(0.05 mg/kg limit of determination) after 42 days, while carbofuran
increased from 0.03 mg/kg at day 0 to 0.09 mg/kg after 21 days. Total
average residues (of duplications) decreased only from 0.15 mg/kg at
day 0 to 0.1 mg/kg after 42 days. Average residues were less than
0.05 mg/kg in all 15-30 cm soil samples.
Because the carbosulfan metabolite dibutylamine (DBA) is a
secondary amine which is theoretically subject to nitrosamine
formation in soil, the stability of dibutylnitrosamine in soil was
investigated to provide information on the likelihood of this
potential hazard (Rogers, 1982). The persistence was investigated in
sandy loam and silt loam soils (pH 5-5.7) either unfortified or with
added nitrate or nitrite. Dissipation was most rapid in unfortified
soil where only 22.5% of the applied nitrosamine was recovered on day
0, decreasing to 0.2% by day 5. Dissipation was also more rapid in
nitrate- than nitrite-fortified soil, decreasing from 29-34% of that
applied on day 0 to 0.9-4.1% after 7 days. The half-life was less than
3 days in all soils. Losses were attributed to volatilization or CO2
formation, but this was not confirmed.
The degradation of 14C-ring- and 14C-DBA-labelled carbosulfan
has been investigated under aerobic and anaerobic conditions. In the
study by Markle (1981a) carbofuran was the predominant ring-labelled
metabolite. In aerobic conditions it increased from 5-12.5% of the
total radioactivity on day 0 to 50% after 14 days; in anaerobic from
40-75% at day 0 to 85% after 14 days. Carbosulfan decreased from
73-86% and 10-34% on day 0 to 2-4% and 0.5-0.7% after 28 days, in
aerobic and anaerobic conditions respectively. Extractables had
decreased to 37-58% (aerobic) and 76-84% (anaerobic) after 28 days,
indicating that bound residues are slower to form under anaerobic
conditions. 3-ketocarbofuran was the next most abundant metabolite
under aerobic conditions, and the 7-phenol under anaerobic conditions.
This suggests that soil binding is oxygen-dependent under aerobic
conditions. Other carbosulfan or carbofuran metabolites were
identified, but at significantly lower levels. The half-life of
carbosulfan in soil was 1-5 days under aerobic conditions.
A 1-5 day half-life of DBA-14C-carbosulfan was also observed
under aerobic conditions (Markle, 1981b) with the rapid formation of
CO2 or DBA. The latter rapidly binds with soil. DBA was present
throughout the study, but did not accumulate. It was also rapidly
formed under anaerobic conditions and accumulated, with less CO2
formation. Unextractable residues were higher under aerobic than
anaerobic conditions, as with ring-labelled carbosulfan.
Residues in rotational crops. Nine months after single applications
of phenyl-ring-14C-labelled carbosulfan at 1.5 and 3 kg a.i./ha to
silt loam soil under field conditions, lettuce, spring wheat and sugar
beets were planted and grown to maturity (Capps, 1980d). The mature
lettuce, spring wheat, and sugar beets were harvested at 60, 90 and
120 days respectively after planting (as were immature plants at
shorter intervals). The radioactivity expressed as carbosulfan in
mature samples from the higher application rate was equivalent to
0.017 mg/kg in lettuce; 0.036, 0.025 and 0.019 mg/kg in the straw,
chaff and grain of wheat respectively, and 0.004 and 0.005 mg/kg in
sugar beet tops and roots. Approximately half these levels were found
at the lower application rate.
Interreaction with soil microorganisms. Three investigations
considered the possible effect of carbosulfan on soil microorganisms
or vice versa. In one (Kinne, 1982), the numbers of microbial colony
populations were not significantly affected within 14 days after an
application of technical carbosulfan at an equivalent field rate of
11 kg a.i./ha to silt loam soil.
In a second study (Froelich, 1982) the effects on nitrification
were investigated after the application of technical carbosulfan to
silt loam and sandy loam soils at field rate equivalents of 11 and
110 kg a.i./ha. Nitrate levels were significantly higher in untreated
controls than in treated samples for 28 days, which was similar at
both rates, was attributed to the acetone solvent since it was also
found in an acetone-treated control. The experiment was not repeated
using a solvent which does not suppress nitrification.
In the third study the effect on cellulose, starch and protein
degradation in silt loam and sandy loam soils was investigated after
applications of carbosulfan at field-equivalent rates of 11 and
110 kg a.i./ha (Froelich and El-Nagger, 1982). No significant effects
were observed in the silt loam, while in sandy loam degradation of
cellulose and starch appeared to be measurably increased. Although a
decrease might have been of concern an increase in degradation was not
considered by the author to be an adverse effect.
In water
The hydrolysis rate of carbosulfan in water in the dark, buffered
at pH 5, 7 and 9 and unbuffered, has been investigated (El-Nagger and
Reynolds, 1982). Half-lives were 0.2, 11.4 and 18.2 hours at pH 5, 7
and 9 respectively. The half-life in distilled water at pH 7.3 was
18.2 hours. The main products from ring-labelled carbosulfan were
carbofuran at pH 5 and 7 and the 7-phenol at pH 9. Low levels of other
carbosulfan and carbofuran degradation products were also detected.
Each was <1% of the total recovered residues at pH 5 and 7 but
at pH 9 3-ketocarbosulfan sulphone, carbosulfan sulphone,
3-hydroxycarbofuran and 3-ketocarbosulfan each accounted for 2-3% of
the recovered radioactivity after 240 hours.
In surface and ground water studies conducted in citrus groves
treated with 5 applications of 2.5 EC (two at 4.2, two at 1.1 and one
at 4.2 kg a.i./ha) carbosulfan was not found ( <0.01 mg/l) in
drainage tile or ditch water in or outside treated plots (Leppert,
1983c). Carbofuran was found inside and outside the treated plots,
initially higher in ditch water than drain tile water. A maximum of
0.64 mg/l was found five days after the maximum application rate,
following substantial rainfall. The pH of the water ranged from 6.5 to
9.2. The maximum carbofuran level outside the treated plots was
0.58 mg/l in the grove ditch, which water entered from the treated
plot. <0.05 mg/l was found down-stream in the grove ditch water
which drained into the county drain system. In general residues
dissipation was related to time, application rate and rainfall.
In storage
Two reports were available on the storage stability of
carbosulfan in soil and in various crops. In one study (Markle, 1980)
the stability of field-incurred residues of carbosulfan and its
metabolite carbofuran was investigated in crops stored up to one year
at -18°C. No losses of carbosulfan or carbofuran, green alfalfa
containing 30 and 3.8 mg/kg or alfalfa hay containing 45 and 12 mg/kg.
In sandy loam and clay loam soils stored at -18°C, approximately
50-60% of the carbosulfan was lost during one year. In clay loam the
loss was accounted for by an equivalent increase in carbofuran. In
sandy loam carbofuran increased by 100% but this did not account for a
significant proportion of the loss. In silt loam degradation of
carbosulfan was almost complete during the 3-hour fortification/
extraction period in repeated attempts. The significant physical and
chemical differences between the silt loam and the other two soils
were a lower pH (4.8, 6 and 6.8) and higher cation exchange capacity
(19.5, 11.8 and 12.9). It was found that leaching was inversely
related to cation exchange capacity and that carbosulfan was
significantly less stable at pH 5 than at pH 7 (see above). Since
degradation has also been shown to be very rapid in dry soil (Capps,
1981; see below), the fact that these samples were dried before
fortification may partly explain the loss.
In the second study untreated green alfalfa, cabbage, corn forage
and potatoes were fortified with carbofuran and stored for periods up
to 21 months at -18°C (Burt, 1982). In green alfalfa carbosulfan
decreased linearly by 40% in 21 months (20% in 12 months for
comparison with the field-incurred residue). The loss was accounted
for by an equivalent increase in carbofuran. In cabbage 50% of the
carbosulfan was lost within 3 weeks, and the sum of carbosulfan and
carbofuran decreased by 40% within this period, so most of the
carbosulfan loss could not be accounted for. Carbofuran alone was
shown to be stable for 12 months in cabbage at -18°C. Losses in corn
forage were approximately 20% in three months and 50% in 12 months.
They were not linear and not fully accounted for by carbofuran
increases since the combined carbofuran and carbosulfan residues
decreased by approximately 10% and 30% in the 3- and 12-month periods.
Carbosulfan was shown to be stable in ethyl acetate, ethanol and
ethanol-acetone solutions. For example 99% was recovered from ethanol
after one month. It was shown to be unstable under acidic conditions
(pH3-5), but stable under neutral or alkaline conditions, over 90%
being recovered after 9 days at pH 9. Under acidic conditions
carbofuran was the major product.
In processing
Citrus. Several studies showed that residues of carbosulfan and its
carbamate metabolites are almost all in the peel (Table 15 FMC, 1984,
1-10, VI-3 and VI-7). The same is largely true of phenolic residues in
oranges (Table 15), and in grapefruit (FCM, 1984, I-9) where peel
residues were >92% of the total. Except on day 0, when the 7-phenol
was higher, the 3-hydroxy-7-phenol predominated in grapefruit whereas
the 7-phenol was predominant at all intervals in oranges.
A citrus-processing study was conducted on Marsh Grapefruit and
Valencia oranges, field-treated four or five times with a total of
approximately 11 kg a.i./ha with a 2.5 EC carbosulfan formulation.
(FMC, 1984, I-2, 5, 18). Average residues of carbosulfan and total
carbamates in whole fruit on the day of last application were:
Oranges Grapefruit
unwashed washed unwashed washed
Carbosulfan 0.17 0.08 0.12 <0.05
Total carbamates 0.73 0.82 0.58 0.44
Average concentration factors for residues in the processed
products are given in Table 16 where the highest concentration factor
for carbamate residues is shown by the oil, followed in order by dried
pulp and molasses. Concentration factors for total phenols increase in
the order oil <dry pulp (11-14% moisture) <molasses, with no
concentration in juice or finisher pulp (80-86% moisture).
Table 15. Average residues in peel, edible fruit and whole fruit - oranges1 (FMC, 1984, I-10; I-23)
Residue, mg/kg2,3
Days
from %
last 3-Hydroxy- 3-Keto- Total Residue
Sample Application Carbosulfan Carbofuran carbofuran carbofuran carbamates in Peel
Edible Fruit 0 (0.01) ND ND ND (0.01)
7 ND ND ND ND ND
14 ND ND (0.01) ND (0.01)
28 ND ND (0.01) ND (0.01)
Peel 0 5.02 0.98 0.21 0.10 6.31 99.6
7 1.21 2.36 0.45 0.43 4.45 99.8
14 0.27 2.00 0.42 0.36 3.05 99.8
28 0.03 1.46 0.55 0.32 2.36 98.8
Residues as 0 1.58 0.31 0.07 (0.03) 1.99
Whole Fruit4 7 0.38 0.74 0.14 0.14 1.40
(Mature) 14 0.08 0.63 0.14 0.11 0.96
28 (0.01) 0.46 0.18 0.10 0.75
3-Keto- 3-Hydroxy- Total
7-Phenol 7-phenol 7-phenol phenols
Edible Fruit 0 ND2 ND ND ND
7 ND ND ND ND
14 ND ND ND ND
28 ND ND ND ND
Table 15. (continued)
Residue, mg/kg2,3
Days
from %
last 3-Hydroxy- 3-Keto- Total Residue
Sample Application Carbosulfan Carbofuran carbofuran carbofuran carbamates in Peel
Peel 0 0.30 ND ND 0.30 100
7 0.30 0.14 0.08 0.52 100
14 0.28 0.15 0.06 0.49 100
28 0.23 0.18 0.08 0.49 100
Residues as 0 0.10 ND ND 0.09
Whole Fruit 7 0.09 (0.04) 0.03 0.16
(Mature) 14 0.09 0.05 (0.02) 0.15
28 0.08 0.06 (0.03) 0.15
1 Two applications of 2.5EC at 1.65 kg a.i./ha, one at early post-bloom and the second 21 days later.
2 ND = none detected (<0.01 mg/kg).
3 Numbers in parenthesis are estimated levels at or above limit of detection and below limit of determination (0.05 mg/kg).
4 Whole fruit residue calculated, assuming a 2.2:1 pulp:peel ratio.
Table 16. Average residue concentration factors for processed citrus products (FMC, 1984, I-2).
Average Concentration Factors1
Processed Valencia Oranges Marsh Grapefruit
Product
3-Hydroxy- Total 3-Hydroxy- Total
Carbosulfan Carbofuran carbofuran carbamates Carbosulfan Carbofuran carbofuran carbamates
Juice NCF2 NCF NCF NCF NCF NCF NCF NCF
Molasses <IX 1.6X 1.3X 1.1X NCF 1.7X 2.9X 2.0X
Dried
pulp <IX 1.2X 5.5X 2.9X <1X 1.1X 4.0X 2.6X
Finisher NCF <1X <1X <1X NCF NCF NCF NCF
pulp
Oil 7.2X 15.2X <1X 7.1X 20.2X 11.3X <1X 7.0X
3-keto- 3-hydroxy- Total 3-keto- 3-hydroxy- Total
7-phenol 7-phenol 7-phenol phenols 7-phenol 7-phenol 7-phenol phenols
Juice NCF NCF NCF NCF NCF NCF NCF NCF
Molasses 8.3X 16.5X 19.1X 16.7X 3.8X 5.3X 11.6X 8.6X
Dry pulp 3.5X 7.5X 9.2X 7.9X 2.5X 4.3X 5.6X 4.7X
Finisher
pulp NCF NCF 0.07X 0.05X 0.25X 0.5X 0.09X 0.2X
Oil 10.8X 4.3X 0.07X 2.6X 3.5X 2.0X NCF 1.2X
1 Concentration factors based on change from unwashed fruit residues.
2 NCF = no concentration factor could be calculated.
Dibutylamine was shown to be concentrated only in dry pulp
(2.1 and 2.4 times in grapefruit and oranges respectively).
Apples. Processed products from apples from trees sprayed with a
2.2 kg a.i./ha 4EC dormant application followed by three 1.1 kg
a.i./ha summer sprays were analysed for carbosulfan and its
cholinesterase-inhibiting metabolites (Witkonton, 1983a) phenolic
residues (Witkonton, 1983b) and DBA residues (Witkonton, 1983c;
Wright, 1983). Samples were harvested on the day of last application.
Concentration factors (Table 17) were 2-4 in wet pomace and 3-12 in
dry pomace. Only 3-hydroxycarbofuran was concentrated, 1.8 times, in
apple cider. Residues in both canned and frozen apple sauce were lower
than in the whole apples from which they were processed.
Photodecomposition
The photodecomposition of carbosulfan has been studied in aqueous
solutions and soils (Capps, 1981). In soil photolysis experiments,
14-ring- and DBA-labelled carbosulfan were applied at 25 mg/kg to a
thin layer of air-dried silt loam soil which was irradiated for
8 days. Decomposition was extremely rapid and, except during the first
10 minutes, there was no significant difference between irradiated
samples and dark controls, indicating that irradiation was not the
controlling factor. Within 10 minutes, ring-labelled carbofuran
accounted for 86.4 and 77% of the recovered radioactivity in
irradiated and control samples respectively. The other prominent
residues in the irradiated sample after 10 minutes were carbosulfan
sulphone 94.5%), the 7-phenol (2.6%) and carbosulfan (1.2%).
Carbofuran was by far the main residue throughout the 8-day
experiment. Dibutylamine (38.6%) was the predominant identified
DBA-labelled residue at 10 minutes. After 8 days 53% was unidentified
(9-10 compounds, none >12.6%), while DBA at 7.7% was still the
predominant identified residue.
Carbosulfan was much more persistent in soil at 70% field
moisture than in dry soil, accounting for 76-98% of the recovered 14C
from 3-48 hours after the application of DBA-labelled carbosulfan
while again there was little difference between irradiated and control
samples or surface and incorporated application.
Ring- and DBA-labelled carbosulfan at a concentration of 5 mg/l
in buffered and distilled water was irradiated (>300 nm sunlamp) at
1500 µw/cm2. In pH 7 buffer, the half-life of the ring-labelled
compound was 1.3 days. After 8 days, carbosulfan and carbofuran
accounted for 1.8% and 59.7% of the 14C respectively. The
corresponding proportions in unirradiated control samples were 46.3%
and 37.6%, indicating the marked effect of irradiation. The half-life
of 14C-DBA-labelled carbosulfan in buffered solutions was similar and
the main identified residue after 4 days was DBA. In unexposed
controls, carbosulfan was still the main residue after 8 days.
Table 17. Carbosulfan and metabolite concentration factors for processed apple products
Residues, mg/kg in whole apples; concentration factors for processed products
Total
3-OH- 3-keto- carbamate 3-keto- 3-OH- Total
Product Carbosulfan Carbofuran Carbofuran carbofuran metabolites 7-phenol 7-phenol 7-phenol phenolics DBA
whole apples
0.24 mg/kg 0.2 mg/kg <0.02 mg/kg 0.07 mg/kg <0.03 mg/kg 0.03 mg/kg 0.23 mg/kg
wet pomace 3.1X 2X 3X UDC1 2.2X 2.9X UDC 2.3 2.8X 4.2X
dry pomace 12.1X 12X 4.6X UDC 10.5X 7.7 UDC 3.3 6.7X 12.4X
apple cider no conc. 0.2X 1.8X UDC 0.6X 0.6X UDC no conc. 0.6X UDC
apple sauce
frozen no conc. 0.2X 0.2X UDC 0.2X 0.6X UDC no conc. 0.4X UDC
canned no conc. 0.2X 0.2X UDC 0.5X no conc. UDC no conc. no conc. UDC
1 UDC - Concentration factor could not be determined because residues in whole apples or product were below the limit of
determination.
In distilled water the half-life of ring-labelled carbosulfan was
4 days. Carbofuran was again the major product of the radioactivity at
4 days while carbosulfan accounted for 53%. The half-life of DBA-
labelled carbosulfan was eight days.
METHODS OF RESIDUE ANALYSIS
An analytical method has been described for the determination of
carbosulfan and carbofuran residues in various crops, water and soil
(Leppert et al., 1983). High-moisture crops were extracted with
hexane and isopropanol; low-moisture crops and soil with 9:2 methanol:
buffer; high-terpene-oil samples (e.g. citrus oils) by acetonitrile
partition from hexane solution, and water with methylene chloride.
Sample clean-up varied according to crop type and included gel
permeation for high-vegetable-oil crops. Additional clean-up was
typically by Florisil column chromatography with hexane: ethyl acetate
eluants, which separate carbosulfan and carbofuran, and by charcoal-
Attaclay-alumina oxide columns. Determination was by gas
chromatography using an unspecified nitrogen-selective detector.
The procedure was validated for various crops (e.g. alfalfa,
rice, citrus, brassica, corn, potatoes, sugar beets), water and soil
at levels down to 0.05 mg/kg for most crops, 0.25 mg/kg for corn and
sugar beets, 0.3 and 0.5 mg/kg for green alfalfa and alfalfa hay
respectively, and 0.005 mg/l for water. Average recoveries were
>75% in all cases and >85% in most. No attempt was made to
define the limit of determination, although a peak at the retention
time of carbofuran which would correspond to 0.02 mg/kg was said to be
the limiting factor. While organosoluble metabolites other than
carbofuran would probably be extracted, conjugated residues would not
be measurable without hydrolysis. The procedure was not tested for
other metabolites.
Recovery of dibutylamine-14C carbosulfan from green or dry
(16% moisture) alfalfa has been shown to be >86% efficient with 2:1
v/v methanol: water or 9:1 v/v methanol: phosphate buffer (Findlay,
et al., 1983).
For the determination of dibutylamine, green alfalfa (Wright,
et al, 1982a) and dry alfalfa hay (Wright, II-7) were extracted
with 2:1 methanol/water, then with dichloromethane after basification.
Samples were derivatized with dansyl chloride, partitioned with hexane
and cleaned up on a Florisil column. Determination was by
electron-capture GC. Recoveries (corrected for controls) were 75 ±3%
(69-79%) for green alfalfa at 1 and 10 mg/kg and 73.9 ±5% (67-77%) for
hay at 3 and 25 mg/kg. The lower fortification levels were at the
limits of determination, while the limits of detection were 0.1 and
0.02 mg/kg for hay and green alfalfa respectively.
The only published method provided to the meeting was that of
Leppert, et al. (1983). In the field residue trials a variety of
analytical methods were used, most of which were similar to the above,
modified for particular situations. Typically carbamates were
extracted with hexane/acetone or methanol buffered at pH 8, cleaned up
by dichloromethane (DCM) partition and Florisil and/or silica column
chromatography, and determined by thermionic GC. Samples were usually
hydrolyzed to release 3-hydroxycarbofuran which was partitioned into
dichloromethane and cleaned up by further partition and column
chromatography before ethoxylation for analysis.
Phenolics were typically hydrolyzed with HC1, partitioned with
dichloromethane, ethoxylated with ethanol under reflux, and
partitioned with DCM under basic and acidic conditions before silica
gel (Sep-Pak) clean-up and analysis by GCMS.
Dibutylamine was typically extracted with 2:1 methanol/water,
cleaned up by several acid and basic DCM extractions, derivatized with
dansyl chloride, cleaned up on Florisil and analysed by
electron-capture GC.
Similar approaches were used for the analysis of poultry
products, except that carbosulfan and carbofuran were extracted with
actenitrile, partitioned with hexane, and cleaned up on
Darco-Attaclay/alumina and Florisil columns. In some cases carbamates
were partitioned with ethanol/ether/hexane, 1:2:1, cleaned up on
gel-permeation columns and determined by HPLC.
Limits of determination varied. They were usually <0.05 mg/kg
for each of the carbamates, but were 0.1 mg/kg in cereal grain stalks,
pome fruit, and grass or clover hay; 0.3-0.5 mg/kg in green grass,
clover or alfalfa and 2 mg/kg in alfalfa hay. The limit of
determination for phenolics where known was also generally
<0.05 mg/kg but was 0.1 mg/kg in stover. Limits of determination
for DBA were <0.05 mg/kg in pome fruit, 0.1-0.2 mg/kg in cereal
grain and stover, and 0.3-0.5 mg/kg in cereal grain stalks and citrus.
In general the analytical methods used in the field trials, if
made available to regulatory authorities, appear to be adequate for
enforcement, assuming further metabolism studies do not reveal other
metabolites which should be determined.
NATIONAL TOLERANCES REPORTED TO THE MEETING
No information was provided.
APPRAISAL
Carbosulfan is a broad-spectrum carbamate pesticide closely
related to its major metabolite carbofuran, a pesticide in its own
right.
Substantial residue data were available but because sufficient
information on nationally approved uses was not provided or was
provided too late for consideration, especially for those countries
where supervised trials were conducted, the meeting could not with any
confidence estimate maximum residue levels which would reflect
established good agricultural practice. The meeting reviewed the data
sufficiently to permit estimation of maximum levels at a future
meeting (for commodities on which data are adequate) when nationally
approved use information (including pre-harvest intervals) and other
required information becomes available. Because sufficient residue
data and information on corresponding proposed agricultural practices
were available, a temporary limit was estimated for citrus fruit.
The fate of carbosulfan has been studied in animals, plants,
soil, water and light, although the meeting did not consider available
metabolic information on animals and plants to be adequate. Carbofuran
is a major metabolite and degradation product of carbosulfan, and
available information indicates that the fate of carbosulfan in these
matrices is to a large extent the same as that of carbofuran. The
major difference in plants is the additional presence of carbosulfan
and (at relatively low levels) various carbosulfan carbamate
metabolites retaining the S-dibutylamine group (e.g. carbosulfan
sulphone, 3-ketocarbosulfan or hydroxy- analogues of these) as well as
dibutylamine which occurs as a major portion of the total residue in
both plants and animals.
Carbosulfan dissipation appears to be similar from WP or EC
applications. The compound is unstable under acidic conditions but
relatively stable under basic conditions. From foliar applications it
is absorbed and metabolized, although translocation, at least in corn
and cotton plants, is towards the extremities. Carbosulfan is rapidly
translocated and metabolized from stem injections.
From soil applications to rice, soybeans and corn there appears
to be minimal uptake of carbosulfan per se, although its principal
metabolites carbofuran, 3-hydroxycarbofuran and dibutylamine (DBA) are
readily absorbed and translocated. Although no plant metabolism
studies were provided for root vegetables, the predominance of
carbosulfan per se, apparently after foliar or soil application,
suggests that translocation and metabolism may differ between root
vegetables and other plants. Metabolism studies on root crops are
needed. Citrus metabolism studies are also desirable as the fate of
residues in citrus may differ from that in other plants investigated.
In plants carbosulfan is typically the predominant residue at or
near the last day of application, while thereafter carbofuran and/or
3-hydroxy-carbofuran tend to be the predominant carbamate residues in
many commodities, the latter primarily as a conjugate. Conjugation
increases with time. There are exceptions as noted above. For example,
carbosulfan was the main residue in clover stems and apples even after
28 days, as it was in some root vegetables at harvest after foliar or
in-furrow granular applications.
3-ketocarbofuran is generally less than 10% of the total
carbamate residue, ranging from undetectable in apples to 20% in
citrus. Depending upon commodity and conditions, phenolics may
typically account for 10-30% of the total residue and DBA has been
found up to 60% in plant metabolism studies.
As in the case of plants, the metabolism picture for animals is
not complete as residues detected in ruminant studies were not
identified. In general, available information suggests that the major
qualitative difference between plant and animal tissue, milk or egg
residues is the absence of carbosulfan or its derivatives retaining
the -S-dibutylamine group in the animal products, whereas they occur
in plants, although (except for carbosulfan itself) at relatively low
levels. However, these compounds have been identified in rat urine.
Low levels (<3% of the residue) of desmethyl carbofuran and
N-hydroxymethyl-3-ketocarbofuran have also been reported in plants,
but not in animal tissues or urine.
A goat study with labelled carbosulfan showed rapid elimination,
primarily in the urine, with residues in milk becoming constant after
about 3 days and containing approximately 2% of the administered
radioactivity. Maximum 14C residues decreased in the order kidney
> liver > milk > other tissues, while fat residues increased during
the withdrawal period. Residues in blood increased throughout the test
period. Residues were not identified, leaving an incomplete metabolism
picture.
In poultry residues reached a plateau at 7-10 days and were
dose-dependent. The 3-hydroxy-7-phenol was predominant in liver and
3-hydroxy-carbofuran in thigh tissues. No carbosulfan or carbofuran
were found in either. From DBA-labelled carbosulfan, DBA was the major
egg residue. Most of the residue was unidentified, although most of
the radioactivity was shown to be incorporated into individual fatty
acids. Egg residues from the ring-labelled carbosulfan study were not
identified.
Conventional poultry feeding studies and metabolism studies
suggest that residues of carbosulfan, carbofuran, 3-hydroxycarbofuran
and 3-ketocarbofuran would all be below their limits of detection
after the consumption of major feed items (corn and sorghum)
containing residues at the highest expected levels.
No conventional feeding studies have been provided for cows.
Until MRLs can be estimated which reflect nationally approved
agricultural practice, and the plant and animal metabolism picture is
more complete, no MRLs can be estimated for animal products.
In soils carbosulfan is only of low mobility, although its major
carbamate degradation product is substantially more mobile.
Dibutylamine is a major non-carbamate product in soil.
In water carbofuran is the major product under acidic conditions
and the 7-phenol under basic conditions.
The stability of carbosulfan in crops and soil under cold storage
varies considerably depending on the commodity and whether the soil is
dry or moist, stability being much higher in moist soils than dry. In
the commodities tested, stability ranged from no loss in citrus after
one year to 50% loss in brassica after three weeks. In some cases the
loss is accounted for by an equivalent increase in the carbofuran
content. Brassica was an exception where the carbofuran increase did
not account for the carbosulfan loss. In general, the validity of
residue data for samples stored for more than a few months (or less in
the case of brassica) becomes increasingly doubtful as the storage
time increases. For many of the residue trials there was no
information on storage conditions or intervals. This is of particular
concern for brassica for which this information should be provided.
There is some evidence that field-incurred residues may be more stable
than residue components added in fortification experiments. Further
information is desirable.
In processing, total carbamate residues in citrus were reduced
somewhat by washing and carbosulfan itself by as much as 50% with most
of the citrus residue being on the peel as it is for apples.
Significant carbamate concentration occurs in citrus processing
products, especially in the oil and dry pulp. Carbamate residues also
concentrate in apple processing products, primarily in pomace and less
in cider.
No information is available on possible residue concentration in
grain milling products and this is desirable. All of these will be of
special significance for the eventual estimation of possible residue
levels in animal products.
Light has little effect on the degradation of carbosulfan in
soil, but it affects degradation in water. In both cases carbofuran
and DBA are the major products.
Analytical methods suitable for enforcement have been developed.
For carbamates extraction is followed by solvent partition, column
chromatographic clean-up and GLC with thermionic detection. For the
determination of 3-hydroxycarbofuran, samples are hydrolyzed and
ethylated before analysis. Methods have also been developed for the
determination of phenolic residues and dibutylamine.
RECOMMENDATIONS
The meeting examined residue data from supervised trials
reflecting, in part, proposed (and possibly current) good agricultural
practice on a number of commodities, and was able to estimate a
maximum residue level for citrus fruit which may occur when
carbosulfan is used as in the trials and when the reported interval
between last application and harvest is observed. The level refers to
the sum of carbosulfan, carbofuran, 3-hydroxycarbofuran and
3-ketocarbofuran.
Pre-harvest interval on which
MRL recommendation is based
Commodity (mg/kg)1/ (days)
citrus fruit 2 28
1/ MRL is temporary irrespective of the status of the ADI until
required information is provided and found by the JMPR to be
satisfactory.
FURTHER WORK OR INFORMATION
Required (1987)
1. Information on nationally registered, approved, or recommended
good agricultural practices. This should include approved
formulations, application rates (a.i./ha) number and type of
applications and intervals between them, interval from last
application to harvest and any other information for the meeting
to determine whether residue field trials data reflect approved
uses. Emphasis should be given to uses in countries where the
trials were conducted or those in close proximity.
2. Metabolism studies on a root crop after uptake from both foliar
and soil treatment.
3. Identification of residues found in ruminants tissues and milk.
4. A conventional ruminant feeding study.
5. Identification of residues found in eggs from ring-labelled
carbosulfan metabolism studies.
6. Further information on the storage conditions and time for
brassica samples. Additional field trials data may be required
with a short harvest-to-analysis interval, depending on the
information provided.
Desirable
1. A citrus metabolism study.
2. Grain processing studies.
3. Further information on storage conditions and intervals for pome
fruit.
4. Additional storage stability data, especially with field-incurred
residues.
5. In addition to other carbosulfan metabolites determined, analysis
of poultry tissues and eggs for 3-hydroxy-N-hydroxycarbofuran,
which has been found in metabolism studies. If found in cow
tissues at significant levels during metabolism studies, those
tissues and milk should also be analysed for this compound in
conventional feeding studies.
6. Information on poultry, egg and tissue residues of dibutylamine
from studies in which it was fed at 10 ppm in the diet.
REFERENCES
Bixler, T.A., Metabolism of Ring-14C and Dibutylamine 14C Carbosulfan
1982 in Alfalfa. Unpublished FMC Report M-4846, May 11, 1982.
Butt, J.E., Carbosulfan Storage Stability Study In/On Various Crops.
1982 Unpublished FMC Report M-4851.
Capps, T.M., Metabolism of Ring-14C FMC 35001 In Rice. Unpublished
1980a FMC Report M-4492, September 17, 1980.
Capps, T.M., Uptake of FMC 35001 Into Rice Plants - Whole Plant Auto-
1980b radiography. Unpublished FMC Report M-4624, December 5,
1980.
Capps, T.M., Metabolism of Dibutylamine-14C FMC 35001 In Rice.
1980c Unpublished FMC Report M-4625, December 8, 1980.
Capps, T.M., Uptake of Soil - Aged FMC 35001 Residues into Outdoor
1980d Rotational Crops - 9 Month Interval. Unpublished FMC Report
M-4619, November 25, 1980.
Capps, T.M., Photodecomposition of FMC 35001. Unpublished FMC Report
1981 M-4648, January 26, 1981.
El-Nagger, S.F. and Reynolds, J.L., Hydrolysis of Carbofuran.
1982 Unpublished FMC Report M-4844, May 6, 1982.
Findlay, C.R. and Witkonton, S., Extractability of Plant Incorporated
1983 Residue From 14-Advantage Treated Alfalfa. Unpublished FMC
Report P-0750, November 2, 1983.
Froelich, L.W., Nitrification Study With Carbosulfan. Unpublished FMC
1982 Report M-4814.
Froelich, L.W. and El-Nagger, S.F., Substrate Degradation Study With
1982 Carbosulfan. Unpublished FMC Report M-4810, March 11, 1982.
Huhtanen, Kurt, Goat Feeding Study With 14-FMC-35001 2,3 Dihydro-2,
1979 2-Dimethyl-7-Benzofuranyl (Di-n-Butylaminosulfenyl) Methyl
Carbamate. Unpublished FMC Report (Cannon Report 9E-4846),
May 15, 1979.
Kinne, L.P., The Effect of Microorganisms on Carbosulfan. Unpublished
1982 FMC Report M-4812. March 12, 1982.
Leppert, B.C., Dissipation of FMC 35001 Residues in Soils From Alfalfa
1981a Fields Following Multiple Applications. Unpublished FMC
Report RAN-0002, March 6, 1981.
Leppert, B.C., Determination of FMC 35001 and Carbofuran Residues in
1981b Soil from Treated Citrus Groves. Unpublished FMC Report RAN-
0024, March 31, 1981.
Leppert, B.C., Determination of Carbosulfan and Carbofuran Residues in
1981c Soil From Treated Citrus Groves. Unpublished FMC Report RAN-
0034, December 8, 1981.
Leppert, B.C., Determination of Dislodgable Carbosulfan and Its
1982 Cholinesterase Inhibiting Metabolite Residues In An Apple
Reentry Study. Unpublished FMC Report RAN-0066, November 19,
1982.
Leppert, B.C., Determination of Carbosulfan And Its Cholinesterase
1983a Inhibiting Metabolites in Eggs From a Poultry And Egg
Residue Study With Carbosulfan Technical and Dibutylamine
Technical In White Leghorn Chickens. Unpublished FMC Report
RAN-0091, June-July, 1983.
Leppert, B.C., Determination of Carbosulfan and Carbofuran Residues in
1983b Soil From a Michigan Apple Orchard. Unpublished FMC Report
RAN-0074, February 3, 1983.
Leppert, B.C., Final Report - Completion of Carbosulfan Surface and
1983c Ground Water Project. Unpublished FMC Report RAN-0076, March
2, 1983.
Leppert, B.C., Markle, J.C., Helt, R.C., and Fujie, G.H.,
1983 Determination of Carbosulfan and Carbofuran Residues in
Plants, Soil and Water by Gas Chromatography. J. Agric. Food
Chem., Vol. 31, No. 2. P. 220-223, 1983.
Markle, J.C., Cold Storage Stability of FMC 35001 Residues in/on
1980 Various Crops and Soils. Unpublished FMC Report RAN-0016.
Markle, J.C., Comparative Soil Degradation of Ring-14C FMC 35001
1981a Under Aerobic and Anaerobic Conditions. Unpublished FMC
Report RAN-0031, September 21, 1981.
Markle, J.C., Comparative Soil Degradation of Dibutylamine-14C FMC
1981b 35001 Under Aerobic and Anaerobic Conditions. Unpublished
FMC Report RAN-0033, December 9, 1981.
Markle, J.C., Identification of 14C-Residues In Tissues And Eggs From
1982a Poultry Administered [Ring-14C] Carbosulfan. Unpublished
FMC Report RAN-0052, June 1, 1982.
Markle, J.C., Identification of 14C-Residues In Tissues And Eggs From
1982b Poultry Administered [Dibutylamino-14C] Carbosulfan.
Unpublished FMC Report RAN-0052, June 1, 1982.
Nishioka, Takaaki; Umetsu, Noriharu; and Fukuto, T. Roy, Side-Chain
Group Metabolism of Dibutylaminosulfenyl Derivative of
Carbofuran In Cotton Plant. Report for Pesticide
Biochemistry and Physiology, provided by FMC, undated.
Reynolds, J.L., Leaching of Carbosulfan and its Aged Soil Residues in
1982 Various Soil Types. Unpublished FMC Report M-4826, March 29,
1982.
Robinson, R.A., Soil Adsorption/Desorption Characteristics of FMC
1980 35001. Un-1980 published FMC Report M-4629, December 29,
1980.
Robinson, R.A., Soil Mobility of FMC 35001. Unpublished FMC Report
1981 M-4647, January 22, 1981.
Rogers, L., Stability and Persistence of Dibutylnitrosamine In Soil.
1982 Unpublished FMC Report M-4835, April 16, 1982.
Tilka, M.A., Determination of Carbosulfan and Its Cholinesterase-
1983 Inhibiting Metabolites in Tissues From a Poultry and Egg
Residue Study With Carbosulfan Technical in White Leghorn
Chickens. Unpublished FMC Report RAN-0093, June-July 1983.
Umetsu, Noriharu; Fahmy, Mohamed A.H.; and Fukuto, T. Roy, Metabolism
1979 of 2,3-Dihydro-2,2-dimethyl-7-benzofuranyl(di-n-
butylaminosulfenyl) (methyl) carbamate and 2,3-Dihydro-2,2-
dimethyl-7-benzofuranyl-(morpholinosulfenyl) methylcarbamate
In Cotton and Corn Plants. Pesticide Biochemistry and
Physiology 10, 104-119 (1979).
Wilkes, Laurie C.; Gustafson, David E.; Adams, Linda; and Wargo,
1981 Joseph P., Jr., 14C-FMC 35001 Poultry Metabolism Study.
Unpublished FMC Research Report ADC Project No. 592, January
14, 1981.
Table 3 References. Table 3 references refer to volume references
1984 in FMC data 1984 package provided to the JMPR. report
numbers and dates are cross-referenced below:
Volume - FMC
Reference Report No. Date
I 1 M-4650 02/02/81
2 -4663 02/27/81
3 -4847 01/25/82
4 -4802 02/22/82
5 -4824 03/29/82
6 -4827 04/05/82
7 -4834 04/13/82
8 -4840 04/26/82
9 P-0541 11/18/82
10 -0642 05/18/83
11 -0654 06/13/83
12 -0663 07/12/83
13 -0664 07/12/83
14 -0747 11/02/83
15 -0748 11/02/83
16 -0749 11/02/83
17 RAN-0020 02/13/81
18 -0021 02/20/81
19 -0028 06/11/81
20 -0040 02/24/82
21 -0044 03/26/82
22 -0077 03/10/83
23 -0080 03/31/83
24 -008 04/15/83
II 1 M-4709 06/16/81
2 -4774 12/10/81
3 -4846 05/11/82
4 P-0488 09/19/82
8 PC-0002 08/27/82
9 -0003 08/27/82
12 RAN-0019 02/13/81
13 -0030 09/11/81
14 -0081 04/08/83
15 -0103 10/04/83
III 1 P-0594 02/25/83
2 -0601 04/13/83
6 -0628 04/15/83
11 -0623 05/03/83
12 P-0624 04/29/83
13 PC-0011 10/03/83
Volume - FMC
Reference Report No. Date
14 M-4855 05/28/82
15 M-4870 08/30/82
16 P-0521 10/15/82
17 PC-0005 09/20/82
18 M-4492 09/17/80
19 M-4624 12/05/80
20 M-4625 12/08/80
21 RAN-0100 09/13/83
IIIa- 22 P-0586 02/04/83
23 P-0671 07/25/83
24 -0738 10/27/83
25 -0760 11/16/83
26 PC-0006 01/17/83
27 -0013 07/25/83
28 RAN-0053 06/10/82
29 -0075 02/08/83
30 -0085 05/31/83
32 -0112 11/11/83
V- 1 P-0566 01/10/83
2 -0593 02/25/83
3 -0690 08/23/83
4 PC-0007 01/26/83
5 RAN-0094 08/25/83
6 -0109 11/08/83
VI- 1 FCC41/821052 01/24/83
2 27/82771 01/25/83
3 40A/82583 05/18/83
4 24/1/821053 01/26/83
5 24/28/42/82/1050 02/25/83
6 17/821049 01/25/83
7 40/8/82584 05/18/83
VII- 1 17 04/15/83
2 none 04/15/80
3 -73/1 1978
4 none 09/10/79
11/14/80
5 FCC 26 11/12/80
VIII- 1 none 04/82
2 none 04/82
3 FCC 39 1981
4 none 04/83
5 none 1981
9 none 09/82
See Also:
Toxicological Abbreviations
Carbosulfan (JMPR Evaluations 2003 Part II Toxicological)
Carbosulfan (Pesticide residues in food: 1984 evaluations)
Carbosulfan (Pesticide residues in food: 1986 evaluations Part II Toxicology)