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)
See Also: Toxicological Abbreviations Ethoprophos (ICSC) Ethoprophos (Pesticide residues in food: 1984 evaluations) Ethoprophos (Pesticide residues in food: 1987 evaluations Part II Toxicology) Ethoprophos (JMPR Evaluations 1999 Part II Toxicological)