PESTICIDE RESIDUES IN FOOD - 1983
Sponsored jointly by FAO and WHO
EVALUATIONS 1983
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
Geneva, 5 - 14 December 1983
Food and Agriculture Organization of the United Nations
Rome 1985
ETHOPROPHOS
TOXICOLOGY
IDENTITY
Chemical Name
O-ethyl S,S - dipropyl phosphorodithioate
SYNONYMS
Ethroprop; ProphosR; MocapR; VC9 - 104
Structural Formula
O
"
C2H50-P-(SC3H7)2
Empirical Formula
C8H19O2PS2
Other Information on Identity and Properties
Molecular weight 242
Physical state clear liquid with yellow tint
Melting point not applicable
Vapour pressure 4.6 × 10-4mm Hg (26°C)
Boiling point 86 - 91°C (0.2 mm Hg)
Partition coefficient 140 (octanol water)
Density 1.094 g/ml (25°C)
Solubility 750 mg/l water (25°C); very soluble in
organic solvents
Stability Thermal stability is good for 12
weeks at 50°C. Very stable in
acid aqueous medium from 25°C to,
100°C; hydrolysis moderately fast
in basic medium at 25°C and rapid
at 100°C.
Flammability not inflammable
EVALUATION FOR ACCEPTABLE DAILY INTAKE
BIOCHEMICAL ASPECTS
Absorption, Distribution, Elimination and Biotransformation
Male and female rats orally treated once with 14C-ethyl-ethoprophos
(1.28 × 106 counts/min/rat) or 14C-propyl-ethoprophos (3 × 106
counts/min/rat) excreted about 55 to 65 percent of the administered
radioactivity in the urine. (Actual dosage of ethoprophos administered
to the animals was not given). Less than 1 percent of the administered
14C was recovered in the faeces. Most of the radioactivity found in
the urine was eliminated during the first six hours post-treatment and
was in the form of hydrolytic products. Among the latter was
O-ethyl-S-propyl phosphorothioic acid, which was the major urinary
metabolite accounting for approximately 40 percent of the given
radioactive dose. Other water-soluble metabolites identified in the
urine included O-ethyl-phosphoric acid, S-propyl-phosphorothiolic acid
and S, S-dipropyl-phosphorodithioic acid. In the urine of rats treated
with the 14C-propyl-labelled compound, organo-extractable
metabolites, viz. methyl propyl sulphide, methyl propyl sulphoxide and
methyl propyl sulphone, were also detected. These latter metabolites
together amounted to about 2 percent of the administered radioactivity
(Iqbal & Menzer, 1972).
In vitro, the NADPH - dependent microsreal enzymes from the liver of
rats and rabbits were able to biotransform 14C-ethyl-ethoprophos or
14C-propyl-ethoprophos to O-ethyl-S-propyl-phosphorothioic acid, the
major metabolite and, depending on the substrate to 0-ethyl-phosphoric
acid (from the ethyl-14C-labelled compound) or
S-propyl-phosphorothiolic acid (from the propyl-14C-labelled
compound). Incubation of liver supernatant preparations from rats and
rabbits with ethoprophos, in the presence of reduced glutathione, led
to the production of O-ethyl S-propyl phosphorothioic acid as the
major metabolite. Additionally, S-ethyl glutathione and
(S-S-dipropyl-phosphorodithioic) acid were formed, respectively, when
the ethyl-14C- or the propyl-14C-labelled compound was used as the
substrate (Iqbal & Menzer 1972).
TOXICOLOGICAL STUDIES
Special Studies on Reproduction
Rat
Groups of 10 male and 20 female rats (Fischer 344, 44-days old) were
fed diets containing technical ethoprophos (95.3 percent pure) at 0,
60.5, 131 or 262 ppm for 56 days prior to mating to initiate a
three-generation (two litters/generation) reproduction study.
Weanlings from the second litters were selected to become parents of
the next generation. All parental animals and weanlings from each
progeny generation were subjected to gross pathological examination.
Additionally, all F1b and F2b parents plus 5 male and 5 female
weanlings per group from F1a, F2a, F3a and F3b litters were
evaluated histopathologically. Mortality was unaffected but growth was
slightly depressed at 131 ppm and above in all parental generations.
Data on food consumption were not available. A dose-related increase
in incidence of dams cannibalizing their young was noted in all
treated groups of the Fo generation, mainly in the second litters.
Pregnancy rate (in percentage) was reduced in all treated groups (75,
60, 55, 55, respectively, at 0, 60.5, 131, 262 ppm) of the F1a
litters and at 262 ppm in F3a and F3b litters. At both 131 and 262
ppm, incidence of litters with at least one dead pup at birth was
elevated in F1b litters and weanling weight (not determined for F1a
and F1b litters) was depressed in F2a and F2b litters. Other effects
that were observed but were limited to the top dosage level included,
e.g. a tendency for decreased litter size at birth through almost all
progeny generations, reduced pup survival from day 4 to weaning in
F1b, F2a and F2b litters, a prolongation of mean gestation period in
F1b litters, occurrence of bilateral lenticular opacity and of
anophthalmia, respectively, in 29 percent and 3 percent of F2a
weanlings (information on litter distribution of these abnormalities
was not available), but in none of the concurrent controls or
weanlings of lower dosage groups, and an increased incidence of
multifocal granuloma of mesenteric lymph nodes in F2b adults. Since
the increase in incidence of Fo dams cannibalizing their young and
the slight decrease in pregnancy rate in F1a litters even at 60.5 ppm
were not recurrent over the generations and were probably related to
maternal toxicity, this level might be considered as a virtual
no-effect level on reproduction (Fletcher et al. 1981).
Special Studies on Teratogenicity
Rat
Groups of 25 to 35 mated female Sprague-Dawley rats (TAC: N(SD)FBR)
were intubated with technical ethoprophos (94 percent pure) at 0,
0.16, 1.6 or 16 mg/kg b.w./day on gestation days 6 through 15 (day 0 =
day vaginal sperm plug observed). The dams were sacrificed on day 20
and the foetuses were removed for gross, skeletal and visceral
examination. Pregnancy rate was comparable in all groups. During, the
gestation period, 1/24 and 18/30 pregnant dams, respectively, at 1.6
mg/kg b.w. and 16 mg/kg b.w. died. Growth was depressed on gestation
days 15 and 20 at 16 mg/kg b.w. There was no significant, difference
between control and treated groups in the mean number of corpora
lutea, implantation sites, live foetuses, dead foetuses or
resorptions, mean foetal weight and sex ratio. According to data
available as summary on skeletal findings and soft tissue
abnormalities in foetuses, the notable observations were a significant
increase in incidence of rudimentary and extra ribs at 1.6 mg/kg b.w.
only and the occurrence of incomplete ossification of the vertebrae in
all treated groups. This latter anomaly, not observed at all in any of
the 169 concurrent control foetuses from a total of 22 litters, was
found at 0.16, 1.6 and 16 mg/kg b.w., respectively with incidences
(percentages) of 10, 7, 17 (the foetus as the sampling unit) or 43,
39, 58 (the litter as the sampling unit). Background data on the
incidence of this particular anomaly were not submitted. It may be
noted that incomplete ossification of the vertebrae also occurred in
82/84 (98 percent) foetuses from 15/15 (100 percent) litters of the
positive control group. The latter, treated with acetylsalicylic acid
at 250 mg/kg b.w., exhibited, a number of other skeletal abnormalities
and soft tissue malformations in the foetuses in addition to maternal
and foetal toxicity. (Knickerbocker & Re 1979).
Rabbit
Groups of 17 female rabbits (New Zealand White), artificially
inseminated were orally treated with technical ethoprophos (95.7
percent pure) at 0, 0.125, 0.5 or 2 mg/kg b.w./day on days 6 through
18 of gestation (day 0 = day of insemination). The surviving does were
sacrificed on day 29 of gestation and foetuses were removed for
external, visceral and skeletal examinations. No treatment-induced
mortality occurred. Does of all treated groups showed an increased
incidence of anorexia during and after the dosing period and a
seemingly dose-related but not statistically significant decrease in
mean body weight gain between days 6 and 18. There were no significant
differences between control and treated groups with respect to
pregnancy rate, mean number of corpora lutea, implantations,
resorptions, dead foetuses or live foetuses, mean foetal weight, mean
foetal crown-rump distance, sex ratio, uterine weight with or without
foetuses, frequency of foetal gross and visceral abnormalities. An
increase in total incidence of skeletal variants was observed in
foetuses of all treated groups. However, the increase was not
dose-related and frequency of any particular type of skeletal variant,
when considered alone, did not follow a dose-response relationship.
The teratogenic no-effect level appeared to be 2 mg/kg b.w. (Wolfe
et al 1981).
Special Studies on Mutagenicity
Ethoprophos, at the non-toxic concentrations ranging from 2.5 to 25
nl/ml, did not induce a detectable level of unscheduled DNA synthesis
in primary rat hepatocytes in vitro (Myhr & Brusick 1981).
Technical ethoprophos was tested for its mutagenic activity in a
murine lymphoma L5178Y specific-locus mutation assay. Under the
conditions of the experiment, the compound did not significantly
increase mutation frequency in the absence of metabolic activation at
concentrations ranging from 0.237 to 0.0316 )µl/ml (showing total
growth for the cultures between 18 and 126 percent) or in the presence
of S-9 mix (from liver of rats induced with Areclor 1254) at
concentrations ranging from 0.0237 to 0.0032 µl/ml (showing total
growth for the cultures between 10 and 106 percent) (Thomson et
al. 1981).
In an in vivo cytogenetic study, groups of male Sprague-Dawley rats
were treated orally with technical ethoprophos (95.7 percent) at O, 2,
9 or 20 mg/kg b.w./day for five consecutive days. The animals were
given colchicine i.p. at 4 mg/kg b.w. four hours after the last dose
and then sacrificed two hours later for metaphase analysis of bone
marrow cells. There was no significant difference between control and
treated groups in the incidence of bone marrow cells with chromosomal
aberrations (Skinner et al. 1981).
Special Studies on Carcinogenicity (See under "Long Term Studies".)
Special Studies on Neurotoxicity
Two groups of ten deep-litter hens (1.4-2.1 kg in weight; age not
specified) were intubated with a single dose of technical ethoprophos
at 5.62 µl/kg b.w. (equivalent to 6.15 mg/kg b.w. and stated to
represent the acute oral LD50 obtained from a previous study
performed at the testing laboratory), or TOCP at 500 µg/kg b.w. Four
untreated hens were used as negative controls. In the
ethoprophos-treated hens, there were no gross signs of ataxia or
paralysis, although symptoms of transient inactivity and "depression"
were noted between 1 and 48 hours. Four hens in this group died within
48 hours of dosing. The positive control birds exhibited clinical
signs characteristic of delayed neurotoxicity. Histopathological
examination of sections of spinal cord and sciatic nerve, stained by
the Weil-Weigert method (not referenced), from birds of negative
control, positive control and ethoprophos-treated groups at the end of
a 21-day observation period reportedly revealed no evidence of
demyelination (Weir & Murphy 1967).
Special Studies on Skin and Eye Irritation
A single application of 0.1 ml of undiluted technical ethoprophos
(equivalent to approximately 44 mg/kg b.w.) to one eye of each of
three New Zealand white rabbits produced moderate erythema and
vascularization of the sclera and nictating membrane in all of the
treated eyes. All three animals died within one hour of treatment
(Weir 1965).
In a primary dermal irritation study, all six male New Zealand White
rabbits with clipped skin exposed under an occlusive patch to 0.5 ml
of undiluted technical ethoprophos (equivalent to approximately 243
mg/kg b.w.) died within the first 8 hours of treatment (Becker & Parke
1977).
Acute Toxicity
The acute toxicity of four animal species to ethoprophos is summarized
in Table 1.
Table 1. Acute Toxicity of Ethoprophos in Animals
Species Sex Route Vehicle LD50 Reference
(mg/kg b.w.)
Mouse M&F oral water 31 Pasquet & Mazuret
(OF1(I.O.P.S.)) 1982
Mouse M dermal acetone 18 Ellison 1979
(CD-1) (24-h
exposure
Rat M oral maize oil 62 Hazleton
(Sprague F 33 Laboratories 1965
Dawley)
Rat M&F dermal water 226 Pasquet & Mazuret
(CD, C.O.B.S.) (24-h 1982
exposure)
Rat M&F inhalation1 none 250 mg/l air2 Kopp et al 1980
(Wistar) (4-h
exposure)
Rabbit F oral ? 33 Schwartz 1978
N.2.W)
Pig M dermal none 327 Rucci 1979
(Yorkshire) (24-h
exposure)
1 Animals were exposed to the liquid technical material as an aerosol in a "nose-only" exposure chamber
with particle sizes < 10 µm
2 Four-hour LC50 expressed as actual chamber concentration.
Signs of oral poisoning
Toxic symptoms noted in the treated species were characteristic of
anticholinesterase poisoning and usually persisted for up to 48 hours
in mice and 72 hours in rats surviving treatment. In general, deaths
occurred within 4 hours (mice) or 1 hour to 3 days (rats) post-dosing.
Information on duration of symptoms and time of death in rabbits was
not available (Pasquet and Mazuret 1982; Hazleton Laboratories 1965;
Schwartz 1978).
Short-Term Studies
Rat
Groups of 25 male and 25 female rats (Charles River Cesarean - derived
strain)were fed diets containing technical ethoprophos in acetone at
0, 0.3, 1 or 100 ppm for three months. (Control group was given basal
diet containing "a volume of acetone equivalent to the volume used for
the test diets"). No mortality or treatment - induced toxic signs were
observed. Growth was depressed (< 10 percent) in males at 1 ppm and
above and in females at 100 ppm during the last six weeks of the
study. Food consumption was unaffected. Haematology, clinical
chemistry and urinalysis performed on 5M and 5F/group at one and three
months indicated no significant compound-related findings. Measurement
of cholinesterase activity in plasma, erythrocytes and brain at four
intervals during the study and terminally showed marked inhibition
(25-100 percent) of the enzyme at 100 ppm in the tissues tested at all
sampling intervals, with the degree of depression being greatest with
erythrocyte cholinesterase and least with brain cholinesterase.
Maximum inhibition of the enzyme occurred on day 8 or 16, Male rats at
both 0.3 and 1 ppm exhibited a reduction (24-28 percent) of
erythrocyte and plasma cholinesterase activity on day 8 and of brain
cholinesterase level at termination. In the females, brain
cholinesterase was inhibited (20-25 percent) at both 0.3 and 1 ppm on
day 8 and at 1 ppm on day 16 also. Additionally, inhibition (23-26
percent) of plasma and erythrocyte cholinesterase occurred at 1 ppm on
day 16. At the end of the study, absolute and relative weights of the
adrenals were elevated in females of all treated groups.
Histopathological evaluation of about 20 selected tissues, including
the adrenal from five males and five females of the control and top
dosage groups, failed to show any significant changes attributable to
inclusion of ethoprophos in the diet. Based on the data 0.3 ppm
appeared to be a minimum-effect level on cholinesterase. For other
monitored parameters, the no-effect level was at least 0.3 ppm (Weir
1967a).
Dog
Groups of three male and three female young adult pure-bred beagles
were fed dietary levels of technical ethoprophos at 0, 1, 3 or 100 ppm
for 13 weeks. There was no mortality. Emesis was noted once in each of
the animals at both 3 and 100 ppm. Body weight, food consumption,
haematological, biochemical and urinalysis values measured at one and
three months were not significantly affected by treatment. Plasma
cholinesterase was inhibited at and above 3 ppm (both sexes) by 27-88
percent at practically all of the seven sampling intervals and at 1
ppm in males by 20-27 percent at the two last sampling periods.
Depression (> 20 percent) of erythrocyte cholinesterase occurred in
both sexes of the top dosage group at all but the first two or three
sampling intervals and in females at 3 ppm on one occasion only. At
termination, no compound-related effects in organ weights or gross
pathological changes were noted. Histopathological evaluation of about
20 tissues from each animal of the control and top dosage groups only
revealed no significant findings other than the observation of a focus
or foci of perivascular myocardial swelling, with loss of striations
in 1/3 female controls and 2/3 M and 1/3 F at 100 ppm. In all of the
three affected dogs at 100 ppm, swelling and vacuolation of Purkinje
fibres were also seen. Such changes were "thought(by the pathologist)
to represent an artifact induced in the processing of the tissues". If
the latter statement could be substantiated or microscopic examination
of the heart(if and when undertaken) from animals of the lower dosage
groups failed to show similar cardiac lesions, 1 ppm might be
considered as a virtual no-effect level for the study (Weir 1967b).
Long-Term Studies
Rat
Groups of 10 male and 10 female rats (Fischer 344) were fed diets
containing technical ethoprophos (95.3 percent) at 0, 60.5, 131 or 262
ppm for 8 weeks prior to mating (one male and two females). (According
to information provided on "Materials and Methods" in the report, the
Fo generation comprised 10 males and 20 females per group. However,
under "Results and Evaluation", it was stated that approximately 16
males and 32 females were mated per dose level. The complete absence
of data on the reproduction phase precluded verification of the
information from either source. It was indicated in the report that
analytical raw data for dietary analysis were not available). Ten days
after the detection of a positive vaginal smear, the females were
separated from the males and were continually maintained on the test
diets until weaning of their pups. This part of the study constituted
the reproductive phase. Weanlings from the reproductive phase (60
males and females per group) were randomly selected from control and
treated groups and fed ethoprophos-treated diets at 0, 4.5, 9 or 18
ppm during weeks 0 to 12 and at 0, 49, 98 or 196 ppm during weeks 13
to 109 of a chronic feeding/oncogenicity study. In this 109-week
study, all animals dying or sacrificed in moribund condition during
the study, all terminal survivors and the ten males and ten females
per group sacrificed after 52 weeks of dietary feeding were subjected
to gross necropsy and histopathological examination of a wide range of
tissues plus all gross lesions.
Data for the reproductive phase were not available. For the 109-week
study, mortality was increased in males of the top dosage group during
the first seven months. The terminal survival rate was, however,
comparable in all groups, including the control. Between 53 and 63
percent of the animals in control and treated groups survived the
entire duration of the study. Other than the appearance of emaciation
in animals of the high-dosage group, there were no compound-related
clinical signs. Growth was depressed in the top-dosage group
throughout the study and in the mid-dosage group through most of the
study. Food consumption was reduced frequently in both sexes of mid
and high-dosage groups during the first 52 weeks. Weekly water
consumption, monitored between weeks 102 and 109, was unaffected.
Haematology, blood chemistry and urinalysis performed at the end of
weeks 52 and 109 revealed a decrease of erythrocyte, haematocrit and
haemoglobin values in males of two high-dosage groups and in females
of the top-dosage group after 52 weeks. Assay of cholinesterase in
erythrocytes, serum and brain, conducted at termination only,
indicated dose-related depression of serum cholinesterase by 71-93
percent and of brain cholinesterase by 30-65 percent in all treated
groups (both sexes). Erythrocyte cholinesterase was not inhibited.
Organ weights analysed at 52-week interim sacrifice and at terminal
sacrifice showed deviations from controls for a number of tissues,
such as spleen, liver, kidney and testis, but these were essentially
limited to the top-dosage level and were not accompanied by
microscopic lesions. Gross pathologic alterations were not
significantly different from those in the controls.
Histopathologically, male terminal survivors at the top-dosage level
exhibited an increased incidence of "scleral mineralization" of the
eye. Microscopic lesions that might be attributable to the compound
were not evident in the other tissues examined.
An evaluation of tumour data indicated the only notable finding as a
statistically significant increase in incidence of thyroid C-cell
adenoma in male terminal survivors at the top-dosage level. Thus,
incidence of the tumour was 2/34 (5.9 percent), 3/31 (9.7 percent),
1/29 (3.5 percent), 9/33 (27.3 percent), respectively, in control,
low-, mid and high-dosage groups. (Calculated as No. of terminal
survivors bearing the tumour/ No. of terminal survivors examined
histopathologically). Only one additional case of C-cell adenoma of
the thyroid occurred among male rats in the study. It was present in
one male of the top-dosage group, which died or was sacrificed in
moribund condition during the study. Data on background incidence of
the tumour in question were not submitted. There was no significant
difference between control and treated groups in the incidence of
animals with tumours (benign and/or malignant), malignant tumours or
multiple primary tumours. It may be noted that interstitial cell
adenoma of the testis in males and pituitary adenoma in females were
the most frequently observed spontaneous tumours in the study, with
nearly 90 percent of males and over 50 percent of females,
respectively, in the concurrent control group being affected by such
tumours (Barnett et al. 1983).
COMMENTS
A limited excretion and elimination study in the rat identified
O-ethyl S-propyl phosphorothioate as a major metabolite in the urine.
Ethoprophos is acutely toxic to rats, mice and rabbits with the oral
LD50 ranging from 30 to 60 mg/kg b.w.
A three generation reproduction study in rats demonstrated no adverse
reproductive effects at a dietary level of 60.5 ppm. Teratology
studies in rats and rabbits were negative for teratogenic effects at
0.16 mg/kg b.w. and 2 mg/kg b.w. respectively. The mutagenicity
studies available, including unscheduled DNA synthesis in primary rat
hepatocytes, a mouse lymphoma assay and an in vivo cytogenetic study
in rats, were negative. A 109-week oncogenicity study in rats showed
an increased incidence of thyroid C-cell adenomas in surviving
high-dose males. Compound-related cholinesterase inhibition was
evident in all dose groups for both plasma aud brain enzymes.
Erythrocyte cholinesterase was not affected. A no-effect level (NOEL)
was not demonstrated in this study.
A delayed neurotoxicity study in hens was inadequate.
A short-term study in rats did not demonstrate a NOEL since
cholinesterase levels were depressed in all treatment groups. A 90-day
dog study demonstrated no adverse effects on cholinesterase at 1 ppm.
The Meeting could not estimate an acceptable daily intake because the
data were inadequate.
REFERENCES - TOXICOLOGY
Barnett, J.W., Jr., Evaluation of the chronic toxicity and
Jenkins, L.J. & Parent, R.A. oncogenic potential of ethoprop in
1983 Fischer 344 rats. Report from Gulf South
Research Institute submitted to WHO by
Rhône-Poulenc Agrochimie. (Unpublished)
Becker, J. & Parke, A primary dermal irritation study of
G. St. E. 1977 ethoprop 93% technical grade on abraded
and nonabraded skin of New Zealand
albino rabbits. Report from Cannon
Laboratories, Inc. submitted to WHO by
Rhône-Poulenc Agrochimie. (Unpublished)
Ellison, T. A comparative dermal toxicity evaluation
1979 in mice (Ethoprop and nine chemical
analogs). Report from Bio/dynamics
Inc. submitted to WHO by Rhône-Poulenc
Agrochimie. (Unpublished)
Fletcher, M.J., Evaluation of effects of ethoprop on
Springer, S.T., reproductive performance by a three-
D'Addamio, G.H., Conzeln & generation reproduction study in Fischer
Pullin, T.G. 344 rats. Report from Gulf South
1981 Research Institute submitted to WHO by
Rhône-Poulenc Agrochimie. (Unpublished)
Hazleton Laboratories V-C 9-104 (Technical grade) Acute oral
1965 administration - Rats. Acute dermal
application - rabbits. Report from
Hazleton Laboratories, Inc. submitted to
WHO by Rhône-Poulenc Agrochimie.
(Unpublished)
Iqbal, Z.M. & Menzer, R.E. Metabolism of O-ethyl S, S-dipropyl
1972 phosphorodithioate in rats and liver
microsomal systems. Biochem. Pharmacol.
21: 1569-1584.
Knickerbocker, M. & Re, T.A. Teratologic evaluation of ethoprop MCTR-
1979 603-78 in Sprague-Dowley rats. Report
from Food & Drug Research Laboratories,
Inc. submitted to WHO by Rhône-Poulenc
Agrochimie. (Unpublished)
Kopp, R., Gunzel, P., Acute inhalation toxicity to the rat
Rosskamp, G., Schmidt, M. & (M&F) of liquid ethoprophos following
Schuppler, J. single 4 hours continuous exposure
1980 (LC50). Report from Schering AG.
submitted to WHO by Rhône-Poulenc
Agrochimie. (Unpublished)
Myhr, B.C. & Brusick, D.J. Evaluation of MOBIL No. 01238101 in the
1981 primary rat hepatocyte unscheduled DNA
synthesis assay. Report from Litton
Bionetics, Inc. submitted to WHO by
Rhône-Poulenc Agrochimie. (Unpublished)
Pasquet, J. & Mazuret, A. Ethoprop (46 095 R.P.). Toxicite aigue
1982 approchee chez la souris par voie orale
et le rat par voie percutanee.
Report from Rhône-Poulenc submitted to
WHO by Rhône-Poulenc Agrochimie.
(Unpublished)
Rucci, G. EthopropR technical grade: MCTR-60-78,
1979 Approximate acute dermal toxicity (LD50)
in young Yorkshire White pups. Report
from Food and Drug Research
Laboratories, Inc. submitted to WHO by
Rhône-Poulenc Agrochimie. (Unpublished)
Schwartz, C.S. Acute oral LD50 determination of ethoprop
1978 in female New Zealand White rabbits.
Letter report to Mobil Oil Company
submitted to WHO by Rhône-Poulenc
Agrochimie. (Unpublished)
Skinner, M.J., Irwin, S.E., Metaphase analysis of rat bone marrow
Schreiner, C.A., cells treated with ethoprop, technical.
Mackerer, C.R. & Report from Mobil Environmental & Health
Mehlman, M.A. Science Laboratory submitted to WHO
1981 by Rhône-Poulenc Agrochimie.
(Unpublished)
Thomson, M.A., A murine lymphoma mutagenesis assay,
Blackburn, G.R. & heterozygous at at the thymidine kinase
Mackerer, C.R. locus for the determination of the
1981 potential mutagenicity of ethoprop.
Report from Mobil Environmental & Health
Science Laboratory submitted to WHO by
Rhône-Poulenc Agrochimie. (Unpublished)
Weir, R.J. & Murphy, J.C. Neurotoxity test - hens. Technical VC
1967 9-104. Final report from Hazleton
Laboratories Inc. U.S.A. submitted
to WHO by Rhône-Poulenc Agrochimie.
(Unpublished)
Weir, R.J. Acute eye application - rabbits. V-C
1965 9-104 (technical grade). Final report
from Hazleton Laboratories Inc.
submitted to WHO by Rhône-Poulenc
Agrochimie. (Unpublished)
Weir, R.J. Three-month dietary administration -
1967 a rats. Technical VC9-104. (Mocap). Report
from Hazleton Laboratories Inc,
submitted to WHO by Rhône-Poulenc
Agrochimie. (Unpublished)
Weir, R.J. 13-week dietary administration - dogs.
1967b Technical VC9-104. Unpublished report
from Hazleton Laboratories, Inc.
submitted to WHO by Rhône-Poulenc
Agrochimie. (Unpublished)
Wolfe, G.W., Durloo, R.S. & Rabbit teratology study. Ethoprop
Phipps, R.B. Technical - 01238101. Final report
1981 from Hazleton Laboratories America, Inc.
submitted to WHO by Rhône-Poulenc
Agrochimie. (Unpublished)