CAPTAN JMPR 1978
Explanation
Captan has been evaluated by Joint Meetings in 1965, 1969,
1973, 1974 and 1977 (FAO/ WHO, 1965b, 1970b, 1974b, 1975b, 1978b).
In 1977 the Meeting advised that further information was required
before it would be possible to determine, with confidence, the MRL
appropriate for cherries. No further information on this topic was
received but the Canadian Government advised that supervised trials
are planned for 1979.
Various countries had submitted information on their current
use patterns and provided new data on the results of residue
trials. The results of further toxicological studies had also
become available for evaluation.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
Special studies on mutagenicity
Captan (93%) was investigated for mutagenic activity in
vitro in the Ames test, using S. typhimurium strains TA 1535, TA
1536, TA 1537 and TA 1538 with and without rat liver microsomes.
Positive results were obtained in the TA 1535 strain.
In an assay using Streptomyces coelicolor, forward
mutations, measured as induction of resistance to low doses of
streptomycin, were studied. Captan (purity 93%) showed a weak
mutagenic activity with a plate technique, whereas the spot test
was negative (Carere et al., 1978).
Captan (> 98%) was administered orally to groups of male rats
(5 animals/group), in a single dose (500, 1000 or 2000 mg/kg), or
at 5 consecutive doses (200, 400 or 800 mg/kg/ day). 21 hours after
the last administration colchicine (2 mg/kg i.p.) was injected and
the animals were sacrificed 3 hrs later. From each animal 50 bone
marrow cells were observed for chromosomal aberrations. No
abnormalities were observed at any dose of captan tested.
In a dominant lethal test groups of 15 male mice were treated
orally with 0, 200 or 600 mg captan/kg/day for 5 successive days.
Then each male was mated with one untreated female. Replacement of
the female was made at intervals of 2-4 days and continued for 6
weeks. Fertilized females were killed 12 or 13 days after
copulation for examination of uterine contents. Male fertility,
mean number of corpora lutea, implants, live embryos, and early and
late embryonic deaths were within normal limits throughout the
experiment.
Cultures of human diploid skin fibroblasts were incubated in
presence of captan. At doses used mitotic inhibition and
cytotoxicity were observed, however no chromosomal aberrations were
induced (Tezuka et al., 1978).
Captan (50 WP, 50% techn. captan) was administered i.p. to
mice in a dose of 0 or 250 mg/kg. 6, 12, 30 and 54 hours following
injection animals were killed and bone marrow cells collected. 5
hours prior to killing, animals were injected i.p. with colchicine
(1 mg/kg). The incidence of chromosomal aberrations did not deviate
significantly from that in controls. However 3 metacentric
chromosomes were observed in 1001 metaphases from captan treated
animals (0/1495 in controls). According to the authors it cannot be
stated with certainty that 250 mg captan/kg i.p. does not break
chromosomes in vivo because of these unique chromosome
rearrangements (Fry and Ficsor, 1978).
Miscellaneous studies
Groups of rats were maintained on a diet containing 24, 8 or
4% protein and 0.01 or 0.1% captan for 12 weeks. Captan toxicity
was increased in the animals kept on protein deficient diets. Due
to protein deficiency the aminotransferase activities were altered.
The fructose diphosphate aldolase activity changed significantly as
a function of both protein deficiency and captan treatment (summary
only) (Urbanek-Karlowska, 1977).
COMMENTS
Positive mutagenicity studies have been noted in several
microbiological systems. In vivo, and in vitro cytogenetic studies
in mammalian systems; as well as a mouse dominant lethal study were
negative.
The Meeting endorsed the opinion of the 1975 Joint Meeting
(FAO/WHO 1976a) that more weight should be attributed to the
results of mutagenic tests in mammalian systems than to those
obtained from microbial or other non-mammalian systems or isolated
all systems. The available mutagenicity data did not, in the
opinion of the Meeting, affect the previously determined Acceptable
Daily Intake.
TOXICOLOGICAL EVALUATION
Level causing no significant toxicological effect
Mouse: 7500 ppm in diet equivalent to 1070 mg/kg bw
Rat: 2000 ppm in diet equivalent to 100 mg/kg bw
Dog: 100 mg/kg bw/day
Monkey: 12.5 mg/kg bw/day
Estimate of acceptable daily intake for man
0 - 0.1 mg/kg
RESIDUES IN FOOD AND THEIR EVALUATION
USE PATTERN
Captan, which was introduced to the market in about 1947 is
approved in most countries for use on a wide variety of fruits,
vegetables, ornamentals, oil and fibre crops and many types of
seed. Information confirmed that it is still widely used for these
purposes with pre-harvest intervals as short as 1 day for some
crops.
RESIDUES RESULTING FROM SUPERVISED TRIALS
The Meeting received details of many trials carried out in the
Netherlands between 1956 and 1975 in which captan was applied to
apples, cherries, pears, currants, raspberries, strawberries,
endive and wheat. Data were received from Denmark on trials on
black currants; from Finland on apples and potatoes; from Japan on
apples, pears, cucumbers, eggplant and tomatoes and from Norway on
lettuce. The residues found at harvest are given in Table 1.
These new data indicate that the MRLs previously recommended
are adequate to cover most of the residues resulting from approved
uses. Exceptions were with (a) currants, where residues 10 days
after application (34 mg/kg) exceeded the MRL (20 mg/kg); (b)
strawberries grown under glass where residues 14 days after
treatment (27 mg/kg) exceeded the MRL 20 mg/kg); (c) endive, grown
outdoors where residues 21 days after treatment (23 mg/kg) exceeded
the MRL (15 mg/kg) and (d) lettuce, where residues 7 days after
treatment (14.0 mg/kg) exceeded the MRL (10 mg/kg). The pre-harvest
intervals mentioned are those approved in the countries concerned.
It may be necessary to review the use patterns in these cases or to
revise the MRLs.
Information was provided from the Netherlands from a trial
done to determine whether there is any significant difference in
the residues remaining on apples following the practical use of
captan by farmers in comparison to those found in supervised
trials. In this experiment apple trees were treated with captan
w.p. at the rate of 1.8 kg/ha according to the directions
appropriate for Gleosporium rot control. Two treatments were
applied 7 days apart and the fruit was harvested 4 and 7 days after
the last treatment.
At the same time apples were collected from 50 commercial
orchards where the growers had used captan under the same regime
(same rate, same number of treatments, same time interval and same
pre-harvest interval). Apples were analysed for captan residues.
The results were as follows:
Days after Residue Coefficient
last treatment (mg/kg) of variance (%)
"Supervised trial" 4 2.01 (0.51-2.45) 25
7 1.99 (0.77-2.60) 32
50 orchards 4 2.46 (0.17-10.3) 85
(practical treatment) 7 2.08 (0.37-5.0 ) 69
Whilst the residues found following practical field use are of
the same order of magnitude as those resulting from applications made
by trained technicians, the range of values is somewhat greater. The
highest levels are still below the recommended MRL.
RESIDUES IN COMMERCE OR AT CONSUMPTION
Data were provided by the Netherlands (1978) from food inspection
monitoring of domestic and imported fruits and vegetables analysed
during 1973/77. With very few exceptions the many samples examined
confirmed with the MRLs recommended by the Meeting.
The New Zealand Ministry of Agriculture advised that during
1971-73, 61 samples of apples were anlaysed for captan residues, with
three positive results ranging from 0.02-0.06 mg/kg.
APPRAISAL
Notwithstanding requests made by the 8th, 9th and 10th Sessions
of CCPR and by the 1976 and 1977 Joint Meetings, no useful data have
been received to answer the question about an appropriate MRL for
cherries.
Information on use patterns was received from various countries
and data from residue trials from Denmark, Finland, Japan, Netherlands
and Norway. These include information on apples, cherries, currants,
raspberries, strawberries, endive, cucumbers, eggplant, lettuce,
pears, potatoes and tomatoes. Results obtained by monitoring fruit and
vegetables moving in commerce were provided by the Netherlands and
data on apples by New Zealand.
None of the information provides a basis or justification for
amending the recommendations made previously but it appears desirable
to recommend an MRL for potatoes.
TABLE 1. Captan residues found in supervised trials
Application Residues in mg/kg, at intervals (days) after last application
Crop and Number of Rate w.p. per
Country treatments treatment kg 0 6 12 20 40
a.i./ha
Netherlands
apple 9 6 g/tree 3.6
(Jonathan) (2.2-5.0)
" 10 6 g/tree 3.3
(1.5-5.0)
" 4 2.5 4.4 2.8 1.0
(3.7-5.4) (2.1-3.6) (0.4-1.5)
" 3 2.5 4.5 6.6 1.4
(4.2-4.7) (6.4-6.8) (0.5-2.4)
apple 9 10 g/tree 6.5
(Goudreinette) (4.6-8.4)
0 6/7 10 14/15 21
apple 1 4 g/tree 3.1
(Golden Delicious) (2.4-4.6)
" 1 4 g/tree 2.4 4.4
(2.0-2.9) (4.1-4.8)
" 13 1.5 1.0 1.3 0.5
" 3 1.5 4.8 5.1 1.4
(4.5-5.2) (4.6-5.6) (0.9-1.7)
TABLE 1. (Cont'd)
Application Residues in mg/kg, at intervals (days) after last application
Crop and Number of Rate w.p. per
Country treatments treatment kg 0 6 14 50
a.i./ha
apple 1 4.0 1.2 0.8 0.9
(Notaris)
apple 1 4.0 1.1 1.0 0.5
(Worchester)
Japan
apple 11 2.5 0.01
1 3.6 0.8
2 2.5 0.04
Finland
apple 1 6 g/tree 17
6 g/tree 20
6 g/tree 1.6
(washed before
analysis)
7 9 10 12 50
Netherlands
sweet cherry 2 22.5 g/tree 7.6
" 2 15 g/tree 9.5
(6-13)
" 2 15 g/tree 3.0
(0.8-4.0)
sweet cherry 2 18.75 g/tree 23.3 12.4
(Meikers) (15.6-29.0) (11.2-14.2)
TABLE 1. (Cont'd)
Application Residues in mg/kg, at intervals (days) after last application
Crop and Number of Rate w.p. per
Country treatments treatment kg 7 9 10 12 50
a.i./ha
pear 9 6 g/tree 6.4
(Bonne Louise) (4.5-8.2)
pear 9 6 g/tree 3.6
(Conference)
Japan
pears 5 0.9-1.6 0.002
" 3 0.9-1.6 0.002
6 10 14 21
Netherlands
red current 2 2.25-2.51) 21.9 21.6 15.9 7.8
(Jonkheer van Tets) (15.6-34.2) (16.2-36.9) (6.0-19.8) (5.2-10.2)
0 7 14 21 28 50
Netherlands
red currant 1 3.751) 9.2 8.3 3.7 2.1
(Jonkheer van Tets) (5.0-13.2) (3.8-11.4) (3.1-4.1) (1.2-2.6)
" 2 3.751) 22.5 17.2 9.6 6.7
(16.3-38.4) (13.5-20.0) (6.3-13.1) (4.4-9.3)
TABLE 1. (Cont'd)
Application Residues in mg/kg, at intervals (days) after last application
Crop and Number of Rate w.p. per
Country treatments treatment kg 0 7 14 21 28 50
a.i./ha
Denmark
black currant 1 1.75 2.28 0.39 1.36
2 2.0 1.3
3 3.2
4 5.2
1 3 6 11
Netherlands
raspberry 2 1.0 5.2 2.1 0.8 0.9
(3.5-8.0) (1.0-4.0) (0.6-1.0) (0.4-1.5)
strawberry 7 1.88 1.7-4.8
outdoor (Chinax)
0 2 4 7 14
strawberry 2 1.88 0.6 0.4 0.4
outdoor (Yucunda) (0.3-0.8) (0.3-0.6) (0.2-0.6)
strawberry 2 2.41) 16.9 18.3 20.5
under glass (Glasa) (12.0-24.5) (15.8-20.0) (15.0-27.0)
10 17 24
strawberry 1 2.41) 13.0 14.6 12.3
under glass (Glasa) (9.9-16.8) (10.6-18.5) (8.0-20.0)
TABLE 1. (Cont'd)
Application Residues in mg/kg, at intervals (days) after last application
Crop and Number of Rate w.p. per
Country treatments treatment kg 0 7 14 21
a.i./ha
endive 3 1.2 15.8 9.0 4.9 1.0
outdoor (11.9-18.7) (7.3-11.0) (2.6-9.8) (0.5-1.3)
Netherlands
endive 3 2.25 82.7 22.2 17.3 15.5
outdoor (40-117) (19-26.5) (10.1-25.1) (6.8-23.0)
" 6 1.5 18.9 18.5 7.3
(14.7-23.1) (16.4-20.8) (6.5-8.6)
" 4 1.5 51.7 21.9 9.6
(44.6-58.6) (17.6-28.2) (6.8-12.3)
2 7 14 21 28 50
Norway
lettuce 1 2.5 7.6-14.0 3.9-6.6 2.9-6.6 4.0-5.6
(greenhouse) (10.8) (5.3) (4.8) (4.8)
Japan
cucumbers 1 3 0.008
5 3 0.04
3 1.8 0.04
2 1.8 0.002
1 2 0.53
0.61
TABLE 1. (Cont'd)
Application Residues in mg/kg, at intervals (days) after last application
Crop and Number of Rate w.p. per
Country treatments treatment kg 2 7 14 21 28 50
a.i./ha
2.14
3 2 0.05
5 2 0.07
5 2.4 2.03
1 1.25 0.36
5 1.1 0.1
1 3.7 0.016 0.005
eggplant 4 1.5 ND ND
tomatoes 1 1.6 < 0.02
1 1.25 0.09
3 1.5 0.01
7 4 0.13
1 4 0.5 0.35
5 1.7 0.8
1 2.4 4.9
3 2.4 1.9
TABLE 1. (Cont'd)
Application Residues in mg/kg, at intervals (days) after last application
Crop and Number of Rate w.p. per
Country treatments treatment kg 2 7 14 21 28 50
a.i./ha
Finland
potatoes 4 1.25 0.01
(unwashed, washed
and peeled)
42
Netherlands
winter wheat 2 0.850 + 2.1 0.01
(Bango) (sulphur) +0.5
(maneb)
winter wheat 2 0.85+2.1(sulphur)+
(Lely) 0.5 (maneb) 0.01
w.p. = wettable powder
1) low volume application
RECOMMENDATIONS
The following additional maximum residue limit if recommended:
potatoes 0.1 mg/kg
FURTHER WORK OR INFORMATION
Desirable
Investigation of the significance of hematoma formation in the
foetus in relation to foetal death or malformation.
REFERENCES
Carere A., Ortali, V.A., Cardamons, G., Torracca, A.M., Raschetti, R.
(1978) Microbiological mutagenicity studies of
pesticides in vitro. Mut. Research, 57, p.
277-286.
Fry, S.M., Ficsor, G. Cytogenetic test of captan in mouse bone
(1978) marrow. Mut. Research, 58, p. 111-114.
Tezuka H., Teramoto, S., Kaneda, M., Henmi, R., Murakami, N.,
(1978) Shirasu, Y. Cytogenetic and dominant lethal
studies on captan. Mut. Research, 57 p.
201-207.
Urbanek-Kaslowska, B. Effect of protein deficiency in rats on
(1977) captan toxicity. Part II. The activity of
selected enzymes in rat serum and liver
depending on dietary level of protein and
captan. Roczn. Panstw. Zakl. Hig., 28 p.
121.132, cited in Pest. Abstr. nr. 77-2446.
See Also:
Toxicological Abbreviations
Captan (HSG 50, 1990)
Captan (ICSC)
Captan (PIM 098)
Captan (FAO/PL:1969/M/17/1)
Captan (WHO Pesticide Residues Series 3)
Captan (WHO Pesticide Residues Series 4)
Captan (Pesticide residues in food: 1977 evaluations)
Captan (Pesticide residues in food: 1980 evaluations)
Captan (Pesticide residues in food: 1982 evaluations)
Captan (Pesticide residues in food: 1984 evaluations)
Captan (Pesticide residues in food: 1984 evaluations)
Captan (Pesticide residues in food: 1990 evaluations Toxicology)
Captan (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
Captan (IARC Summary & Evaluation, Volume 30, 1983)