ALDRIN/DIELDRIN JMPR 1977 Explanation Dieldrin was reevaluated at the Joint FAO/WHO Meeting in 1970 (FAO/WHO 1971) and additional information on the significance of the hepatic lesions observed in mice after dieldrin treatment was thought desirable. Moreover further data on long term studies of industrial workers, on teratogenicity, on comparative metabolism studies in humans, monkey rat and mouse and data an possible photo-dieldrin residues in foodstuff should become available for evaluation. Since that last reevaluation results of several studies have been presented and are summarized in the following monograph addendum, together with data on the teratogenicity and carcinogenicity of aldrin. EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Absorption, distribution, excretion and biotransformation Dieldrin has been reported to produce hepatoma in certain mice strains not however in other laboratory animals so far studied. Different metabolic pathways and differences in excretion could be the reason for this possible species-specific reaction of mouse liver on the ingestion of dieldrin. A comparative metabolism study in mice (strain Swiss White), rats, rabbits, rhesus monkeys and chimpanzees showed that there are two main metabolic pathways in mammals. The first involves direct oxidation, supposedly by cytochrome oxidases, resulting in 12-hydroxydieldrin, the second involves the opening of the epoxide ring by epoxide hydrases resulting in aldrin-4,5-trans-dihydrodiol. Single oral doses of 0.5 mg/kg of 14C labelled dieldrin were administered to the test animals. Faeces and urine were collected separately for 10 days following administration. The major metabolites in the excreta of all five species under study were 12-hydroxydieldrin and 4,5-aldrin-transdiol. In all species the faecal excretion of unchanged dieldrin was high in the first 48 h after administration and declined rapidly thereafter. The urine contained no unchanged dieldrin. Regarding the ratios of the two major metabolites, the rats and primates seemed to metabolize dieldrin mainly by direct oxidation resulting in 12-OH-dieldrin, whereas the common main metabolic pathway of mice and rabbits seemed to be the opening of the epoxide ring to the diol. The highest rate of metabolism was found in the mouse with 33% of the administered dieldrin being metabolized within 10 days, compared to about 9% in rats, 2% in rabbits, 11% in rhesus monkeys and 3% in chimpanzees. The high rate in mice may result in relatively high diol concentrations in the mouse liver. About 23% of the administered dose was excreted as aldrin-trans-diol by mice compared with only 1-2% in the other species examined (Müller at al., 1975a). Similar results were also obtained by Bedford and Hutson (1976). 14C labelled dieldrin was administered to rhesus monkeys either as a single i.v. injection of 2.5 mg/kg or as a single oral dose of 0.36 or 0.5 mg/kg. The excreta were separately collected for 75 days following administration. After administration by injection there was a short period of relatively high excretion; 13% of the administered dose was eliminated within the first 5 days. The excretion rate decreased to about 0.05% per day after 20 days. A total of 20% was excreted over the whole period. Only 10% of the excreted radio-carbon was eliminated with the urine during the initial excretion phase, after day 20 the urinary excretion rate increased to 30-40%. The three identified metabolites found in the excreta were 12-hydroxydieldrin, 4,5-aldrin-trans-dihydrodiol and the last one was assumed to be a glucuronic acid conjugate of the diol. After oral administration 17% and 25% of the administered dose respectively were eliminated within 10 days at the 0.36 and 0.5 mg/kg dose level. The faeces contained predominantly dieldrin for the first two days. From the third day urine and faeces contained the same metabolites found in the injection study. 7% and 11% respectively were excreted as unchanged dieldrin, 8% and 12% respectively as 12-hydroxydieldrin in the monkeys treated with 0.36 mg/kg and 0.5 mg/kg (Müller et al., 1975b). Determination of the faecal and urinary radioactivity during the 7 days following a single oral dose of 14C-dieldrin to different rat and mouse strains showed that the major route of excretion is via the faeces. The nature of the excreted metabolites and the excretion rates of individual metabolic products depended on species, strain and sex. The major faecal metabolite in rat and mouse was syn-12-hydroxydieldrin, the excretion rate of this metabolite being much higher in rats than in mice. On the other hand the production of the trans-diol was higher in mice than in rats. Similar amounts of the tricyclic diacid were excreted in both species. Unchanged dieldrin was also excreted via the faeces in rats and mice. Most of the urinary label in the male rat (CFE strain) was dieldrin pentachloroketone; this metabolite was found only in traces in the urine of female rats or mice. Unchanged dieldrin and the diacid were excreted in the urine of both rat and mouse. The investigation of the metabolites in organs and tissues of rats showed that dieldrin was present in all organs and tissues, the adipose tissue being the major site of deposition. Dieldrin pentachloroketone was also present in most tissues and organs, notably in the kidney of male animals. No other metabolites were detected. The monohydroxylated metabolite of dieldrin, syn-12-hydroxydieldrin is formed after incubation of dieldrin with rat liver microsomes. Since the production can be inhibited in vitro by the addition of mono-oxygenase inhibitors such as sesamex, syn-12-hydroxydieldrin is obviously formed by liver microsomal monooxygenase action. The bridged pentachloroketone is also a sesamex-inhibited product of dieldrin incubation with liver microsomes and seems to be formed also by monooxygenase activity. It has been assumed that the trans-diol is formed by the action of epoxide hydratase upon dieldrin. The formed cis-diol is converted into the ketol by oxidation and the reduction of the latter would lead to the trans-diol. Based on the results of recent studies a novel pathway of the trans-diol formation is proposed involving direct oxidative formation of the ketol from dieldrin, reduction of which yields the cis- as well as the trans-diol. In vitro experiments with cis- and trans-diols indicated that the cis-diol was convertible into the trans-diol, but that the reverse reaction did not occur (Bedford and Hutson, 1976). TOXICOLOGICAL STUDIES Special studies on mutagenicity The compound did not produce any mutagenic response when tested in vitro with or without microsomal activation against five indicator organisms of histidine auxotroph tester strains of Salmonella typhimurium. Tester strains that revert due to base analogue and frameshift mutation in repair deficient as well as repair competent strains had been utilized. Additionally two strains were examined that are deficient in their lipo-polysaccharide coat which allows for penetration of lipophilic compounds (Bidwell et al., 1975). Preliminary results of a microbial mutagenicity study showed that also metabolites of dieldrin, i.e. syn-12-hydroxydieldrin, aldrin dicarboxylic acid, cis-aldrin diol, trans-aldrin diol and pentachloroketone did not significantly increase the incidence of reverse mutations of six histidine auxotroph tester strains of Salmonella typhimurium (Dean and Brooks, 1977). For the evaluation of possible host-activated mutagenic metabolites of dieldrin, host-mediated assays and blood-and urine recovery studies were performed in mice. The animals were treated daily for 5 days with an oral dose of 20 mg/kg and then received injections of tester bacteria. Mutation frequencies showed no significant increase in mutation in the dieldrin-treated animals (Bidwell et al., 1975). No mutagenic activity could be found in a further host-mediated assay. Mice were treated with a single oral dose of 25 and 50 mg/kg dieldrin (HEOD) or with repeated doses of 5 and 10 mg/kg on five consecutive days. The indicator organism, injected after the fifth dose into the peritoneal cavity, was a strain of the yeast Saccharomyces cerevisiae (Dean at al., 1975). The examination of blood and urine samples of mice treated with a single oral dose of 20 mg/kg by spot test revealed no mutagenic substances in blood or urine treated animals (Bidwell et al., 1975). After oral treatment of male mice with 12.5, 25 and 50 mg/kg dieldrin (HEOD) and mating with untreated females in a dominant lethal test no adverse effects could be observed (Dean et al., 1975). Consistent results were obtained when mice were treated with 0.08, 0.8 and 8 mg/kg dieldrin for 5 consecutive days before mating with untreated females (Bidwell et al., 1975). The oral administration of single doses of 30 and 60 mg/kg dieldrin (HEOD) to Chinese hamsters did not cause any demonstrable chromosome damage in bone marrow cells (Dean et al., 1975). Standard metaphase analysis and micronuclei test after oral treatment of mice with 0.8 and 8 mg/kg dieldrin for 5 days revealed no cytogenetic abnormalities (Bidwell at al., 1975). The heritable translocation test was carried out with male mice that sired low numbers of pups after oral intake of 0.008, 0.08 and 0.2 mg/kg over a period of 6 weeks. The cytogenetic determination of somatic cells utilizing the micronuclei test and the usual analysis of spermatocytes did not reveal an increase in the number of trans-locations that could have led to sterility or semisterility (Bidwell et al., 1975). Special Study on Teratogenicity Foetotoxic and teratogenic effects were found after administration of aldrin and dieldrin as single oral doses to hamsters and mice. Hamsters were treated with 30 mg/kg of dieldrin and 50 mg/kg aldrin on gestation day 7, 8 or 9, mice were treated with 15 mg/kg dieldrin and 25 mg/kg aldrin on day 9 of gestation. Foetotoxicity in hamsters resulted in an increase of foetal death and foetal growth retardation. High incidences of congenital anomalies such as cleft palate, open eye and webbed foot were found as teratogenic defects. In treated mice similar anomalies were found but without increase of foetal mortality and growth retardation (Ottolenghi at al., 1974). After daily oral administration of 1.5, 3 and 6 mg/kg dieldrin and 0.15, 0.3 and 0.6 mg/kg photodieldrin to mice and rats on gestation days 6 through 16 no teratogenic effects were observed even at the highest dose levels. The administration of 6 mg/kg dieldrin resulted in a reduction of the average body weight gain in mice and rats, an increase of the relative liver weights in mice and a 41% mortality in rats. The highest dose of photodieldrin resulted in increased liver weights in mice and a 15% mortality in rats (Chernoff et al., 1975). No teratogenic activity of the compound could be found when dieldrin (HEOD) was orally administered at dose levels of 1.5 and 4 mg/kg in corn oil or 1.25, 0.5 and 1 mg/kg in DMSO to mice on days 6 through 14 of gestation. The only adverse effects such as reduced body weight gains of the pregnant mice, some maternal deaths, lower foetal body weights and increased incidence of delayed ossification of the foetal bones were observed in the control and treatment groups when DMSO was used as vehicle (Dix et al., 1975). Special Study on Carcinogenicity Mouse Groups of 50 mice of each sex were maintained on a diet containing dieldrin at doses of 2.5 and 5 ppm for a period of 80 weeks followed by an observation period of 10-13 weeks. Matched controls consisted of groups of 20 untreated male and 10 untreated female mice. Pooled controls used for statistical evaluation consisted of the animals in the matched control group combined with 92 male and 79 female untreated animals from similar bioassays with other chemicals. All surviving mice were killed at weeks 90-93. The treatment did not affect the mean body weights or the survival rates. During the second 6 months of the study clinical signs such as tremors, abdominal distention, alopoecia, tachnypnea and hyperexcitability appeared among treated animals and increased in frequency during the second year of study, together with pale mucous membranes and rough hair coat. In male mice there was a marked dose-related increase in hepatocellular carcinomas showing frequencies of 17/92 (18.5%) in the pooled controls, 12/50 (24%) in the 2.5 ppm group and 16/45 (36%) in the 5 ppm group. The incidence of hepatocellular carcinoma was much higher in male animals of the control and treated groups than in females. The incidence in females was not dose-related. 3.8% of the females in the pooled control group showed heptocellular carcinoma, 12% in the low and 4% in the high dose groups. There was a low incidence of other types of neoplasms involving various organs and tissues with no obvious difference between control and treated animals (NCI, 1977a). Groups of 50 mice of each sex were administered aldrin at time- weighted dietary average doses of 4 and 8 ppm for males and 3 and 6 ppm for females. The diet was administered over a period of 80 weeks, then the animals were observed for 10-13 weeks. The control groups included the matched control animals and the 92 male and 79 female untreated mice from the pooled control group. All surviving mice were killed at 90-93 weeks. The treatment did not affect the mean body weights. During the second year of the study, clinical signs including rough hair coat, alopecia and abdominal distention appeared with increasing frequency. No dose-related increase in mortality in the male mice was found, whereas in female mice there was a dose-related trend in mortality represented by early deaths in the high-dose group. A dose-related increase of hepatocellular carcinomas in the treated male mice was seen with incidences of 10.8% in pooled control group, 33% in the low dose group and 54% in the high dose group, whereas the frequency of this neoplasm in the female mice was much lower and not dose-related with incidences of 2.3% in pooled controls, 10% in the low dose and 5% in the high dose group. The low incidences of other types of neoplasms in various organs and tissues were not considered to present a difference between treated and control groups (NCI, 1977a). Groups of 50 rats of each sex were administered dieldrin at time- weighted average dietary dose levels of 29 ppm for a period of 80 weeks followed by an observation period of 30-31 weeks and 65 ppm for 59 weeks, followed by 51-52 weeks of observation. Matched controls consisted of groups of 10 untreated rats of each sex. Pooled controls used for statistical evaluation, consisted of the matched-control groups combined with untreated animals from similar bioassays of other chemicals, 58 male and 60 female rats. All surviving rats were killed at 110-111 weeks. Mean body weights showed no difference compared with those of the controls during the first year of the study; however during the second year the treated animals showed lower weights than the control. During the first 6 months of treatment the treated animals were comparable to the controls with respect to behaviour and appearance with the exception of high-dosed animals having convulsions. During the second 6 months of the study clinical signs including diarrhoea, alopoecia, epistaxis, haematuria, discoloured hair coats, tremors and weight loss appeared and increased in frequency during the second year of study, together with pale mucous membranes, vaginal bleeding, dermatitis, dyspnoea, ataxia, tachypnea, abdominal distention, rough hair coats and discoloured urine. There was a marked increase in the mortality rate of rats during the first 90 weeks of the study. However because of the high rates of mortality in the control groups during the remaining study period, mortality did not appear to be treatment-related. A significant increase was found in the combined incidence of adrenal cortical adenoma and carcinoma in the low-dosed females (6/45) compared with the pooled controls (0/55). No dose-relationship could be seen. There were instances where neoplasms occured only in treated animals (adrenal cortical adenoma, spleen haemangiosarcoma) or with increased frequency when compared to control groups (pituitary chromophobe-adenoma). Incidence and severity of the lesions were not considered to provide clear evidence of a carcinogenic effect of dieldrin on rat (NCI, 1977). Groups of 50 rats of each sex were maintained on a diet containing aldrin at dose levels of 30 to 60 ppm. Male rats were treated for 74 weeks, followed by 37-38 weeks of observation, female rats were treated for 80 weeks, followed by an observation period of 32-33 weeks. Matched controls consisted of groups of 10 untreated rats of each sex. Pooled controls consisted of the matched-control groups combined with 58 untreated males and 60 untreated females from other bioassays. All surviving rats were killed at 111-113 weeks. During the second year of the study mean body weights of the treated animals were lower than those of the control animals. Hyperexcitability was observed in all treated groups with increasing frequency and severity during the second year. The mortality was not dose-relatedly affected by the treatment. During the second 6 months of the study convulsions were observed in several high-dosed female rats. Throughout the second year of the study clinical signs including pale mucous membranes, rough hair coats, weight loss and vaginal bleeding were apparent in all treated groups. The combined incidence of follicular-cell adenoma and -carcinoma of the thyroid was increased in both sexes. These incidences however were significantly increased only in the low-dose animals compared with the pooled controls. Adrenal cortical adenoma incidence showed a significant increase compared with pooled controls in the low-dose females. There were instances where neoplasms occurred only in the treatment groups or with increased frequency compared with those in control groups. The incidence of tumors and the severity of lesions are however not considered to be dose-related (NCI, 1977a). Groups of 24 Fischer 344 rats of each sex were administered dieldrin technical grade, purified and recrystallized, at 0, 2, 10, or 50 ppm, for 104-105 weeks. The dose level of 50 ppm constitutes a maximum tolerated dose. All surviving rats were killed at 104-105 weeks. Body weights of the rats were essentially unaffected by the treatment, but typical signs of organochlorine intoxication including hyperexcitability, tremors and coma were observed in high-dose males beginning in week 76 and in high-dose females beginning in week 80. Survival was not adversely affected, and adequate numbers of rats were available for meaningful statistical analysis of the incidence of tumors: 67-70% of the high dose group, 75-83% of the mid-and low-dose group, and 88-92% of the matched control group survived to the termination of the study. A variety of neoplasm occurred in control and treated rats; however, the incidences were not related to treatment. Frequently interstitial-cell tumours of the testes (80-100%), and lymphocytic and granulocytic leukaemia (8-21%) occurred. It is concluded that under the conditions of this bioassay, dieldrin was not carcinogenic in Fischer 344 rats (NCI, 1977b). Hamster 145 female and 147 male Syrian hamsters received dietary concentrations of 0, 20, 60 and 180 ppm dieldrin (purity 99%) for life. The survival rate at 50 weeks of age was comparable to the control being 66%. Among control females 12% showed tumors whereas in treated females 3-15% had tumors. 8% of the control males had tumors and between 16 and 23% of the treated males. The study showed that by the treatment of hamsters no significant increase in tumor incidence is observed (Cabral at al., 1977). In view of the possible species-specific reaction of mouse liver to ingested dieldrin several studies have been performed on the interactions of dieldrin with liver cells at the subcellular level in different mammalian species (Wright at al., 1977). The earliest structural change observed in the livers of rats, mice and dogs treated with dieldrin was the proliferation of the smooth endoplasmic reticulum (SER). During the initial phase of the exposure to dieldrin the increases in the SER in rats, dogs and mice were of the vesicular type. Thereafter as an effect of microsomal enzyme induction intracellular whorls of smooth membranes appeared in the liver cells of rats and dogs. None of these structures was induced in mice liver. All these structural changes were reversible. In contrast no structural changes in the livers of rhesus monkeys were observed. Dieldrin administered in large doses caused liver enlargement in the rat, mouse and dog but not in monkeys. In vitro determinations, being the most sensitive criterion for the effect produced by dieldrin, showed that the activity of the liver microsomal monooxygenase system was increased after treatment. Microsomal enzyme induction was detected in all four species exposed to dieldrin. A dietary concentration of about 1 ppm was reported to be sufficient to produce monooxygenase induction in rat liver. The possibility that dieldrin or one of its metabolites exerts its tumorigenic action on mouse liver by means of a direct interaction with DNA has been studied measuring the extent of binding of 14C-labelled dieldrin and/or its metabolites to liver DNA utilizing one rat strain and two mouse strains. CF1 mice are susceptible to liver tumor induction by dieldrin, whereas LACG mice represent a strain which is not or only very weakly susceptible. The results showed that the extent of binding was not correlated with susceptibility. Binding was highest in the rat, intermediate in the susceptible and lowest in the non-susceptible mouse strain. Based on these results on the one hand and the uniformly negative results of different mutagenicity tests on the other, the conclusion is drawn that the increased incidence of liver tumors in dieldrin-treated mice is not due to direct damaging effects on DNA. Experiments determining the rate of semi-conservative DNA synthesis in normal primary human fibroblasts (AH) as well as experiments determining repair replication in AH cells and SV-40 transformed human cells also gave no indication of damage to DNA or induction of repair replication after treatment with dieldrin (Zelle and Lohman, 1977). The treatment of SV-40 transformed human cells in culture with dieldrin resulted in increased unscheduled DNA synthesis and in induction of DNA repair. They reported that in these treated human cells long-type excision repair of DNA could be found (Ahmed et al., 1977). Observations in Humans Previous results of a long term study of occupationally exposed industrial workers (Jager, 1970) were presented at the Joint FAO/WHO Meeting in 1970 (FAO/WHO, 1971). A follow-up survey of the study has been carried out (Versteeg and Jager, 1973). The figures from this continuing study were updated. The population under study numbered about 1,000 persons. Because not all of the workers had prolonged and severe exposure, smaller groups with exposure meaningful enough for carcinogenicity evaluation were taken. One group consisted of 166 men (including still exposed, still employed workers, and also workers who left the company) with a mean exposure time of 16.9 years (range 4-19) and more than 15 years of observation (mean observation period 17 years, range 4-20). A sub-group of these comprised 69 men with a mean exposure time of 14.9 years (range 10-19) and a mean observation period of 17.2 years. Among these 166 workers, 51 were older than 50 years. One man with only 5 years of comparatively mild exposure died because of a gastric carcinoma. A lymphosarcoma occurred in a man with 7 years of very mild exposure. Both incidences occurred before 1964. No new cases were noted in the last 11 years and no undue mortality from other causes that could have marked a higher cancer incidence was observed. The organochlorine pesticide concentrations of dieldrin, pp'DDE, pp'DDD, pp'DDT, gamma-HCH, ß-HCH and HCB have been determined in the blood from mothers and their babies as well as in mother's milk. The results showed no evidence that breast-feeding resulted in higher dieldrin concentrations in the blood of the babies than did bottle-feeding. There was some evidence that the placenta restricted the transmission of the pesticides to some extent. The daily intake of dieldrin by mothers was assessed at 7-20 µg/person in the diet of the U.K. population. Between 12 and 21% of the estimated daily intake of dieldrin by mothers may be eliminated by lactation during the first 3 months after birth. Based on an average daily dieldrin intake of 10 µg/person a baby's daily intake could increase to 1.2-2.1 µg or 0.3-0.5 µg/kg b.w. (Van Raalte, 1977). COMMENTS The required teratogenicity studies in different animal species were submitted and showed dieldrin not to be a teratogen. In several studies where the test compounds were administered in repeated small doses to pregnant mice no teratogenic effect could be found. However, the administration of a single high dose of 15 mg/kg dieldrin to mice (1/2 LD50) or 30 mg/kg to hamsters resulted in minor malformations which were attributed to maternal toxicity. Results of various carcinogenicity tests in mice and other mammalian species indicate that there is a species-specific effect of dieldrin and aldrin on the mouse liver, resulting in an increased frequency of liver tumors only in this animal species. In all species examined (mouse, rat, rabbit, rhesus monkey, chimpanzee) 12-hydroxydieldrin and 4, 5-aldrin-trans-dihydrodiol were the major metabolites. Regarding the ratios of these two metabolites the mouse seems to metabolize the test compound predominantly by the opening of the epoxide ring. This metabolic pathway on the one hand and a high rate of metabolism compared with other animal species examined on the other, could result in relatively high concentrations of 4, 5-aldrin-trans-dihydrodiol in the mouse liver. Dieldrin, as well as other chlorinated pesticides, is a powerful inducer of microsomal enzymes. Owing to their high rate of metabolism, mice are especially susceptible to such effects (see section 3.1). Compared with other animal species, it reacts rather anomalously and the mouse, therefore, may not be an appropriate model for humans in this case. The results of prolonged enzyme induction are proliferation of the endoplasmic reticulum in the cells, and hypertrophy and hyperplasia of the liver. These changes are fully reversible if treatment is ceased before tumours have developed on the chronically over-loaded and damaged cells. Similar effects are produced by phenobarbital. The results of the different experiments for the study of the possible mechanism of the tumorigenic action of dieldrin on mouse liver at the sub-cellular level are inconsistent. A number of in vitro and in vivo mutagenicity tests have been performed. In none of these studies did dieldrin reveal any mutagenic activity. These new findings again support the view that dieldrin and aldrin are not carcinogens on the basis of knowledge available to the Meeting. Therefore no change of the existing ADI for humans me considered necessary. TOXICOLOGICAL EVALUATION Level causing no toxicological effect Rat: 0.5 mg/kg in the diet, equivalent to 0.025 mg/kg bw Dog: 1 mg/kg in the diet, equivalent to 0.025 mg/kg bw ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR HUMANS 0-0.0001 mg/kg bw* FURTHER WORK OR INFORMATION * the ADI is applicable to aldrin and dieldrin separately or to the sum of them if both are involved. Desirable 1. Further studies on the possible mechanism of the tumorigenic action on mouse liver. REFERENCES Ahmed, F.E., Hart, R.W. and Lewis, N.J., (1977) Pesticide induced DNA damage and its repair in cultured human cells. Mut. Res. 42, 161-174. NCI (1977a) Bioassays of Aldrin and Dieldrin for Possible Carcinogenicity. Carcinogenesis Program, Division of Cancer Cause and Prevention. National Cancer Institute, National Institutes of Health. NCI (1977b) Bioassay of Dieldrin for possible Carcinogenicity. Carcinogenesis Program, Division of Cancer Cause and Prevention. National Cancer Institute, National Institutes of Health. Bedford, C.T. and Huston, D.H., (1976) The comparative metabolism in rodents of the isomeric insecticides dieldrin and endrin. Chemistry and Industry, 15 MAY 1977, 440-447. Bidwell, K., Weber, E., Nienhold, I., Connor, T. and Legator, M.S., (1975) Comprehensive evaluation for mutagenic activity of dieldrin. Presented at 6th annual meeting of Environ. Mutagen Soc. Miami Beach, Fla. Cabral J.R.P., Shubik, P., Bronczyk, S.A. and Hall, R.K., (1977) A carcinogenesis study of the pesticide dieldrin in hamsters. Paper given at 68th annual meeting Am. Assoc. Cancer Research and 13th annual meeting Am. Soc. Clin. Oncology, Denver Col. USA (Mau 1977). Proceedings Abstract 111, 28 Chernoff, N., Kavlock, R.J., Kathrein, J.R., Dunn, J.M. and Baseman, JJ., (1975) Prenatal effects of dieldrin and photodieldrin in mice and rats. Tox. appl. Pharmacol. 31, 302-308. Dean, B.J., Doak, S.M.A. and Somerville, H., (1975) The potential mutagenicity of dieldrin (HEOD) in mammals. Fd. Cosmet. Toxicol. 13, 317-323 Dean, B.J. and Brooks, T.M., (1977) Microbial mutagenicity studies on dieldrin metabolites. Preliminary results report. Shell Toxicology Laboratory (Tunstall), 30th August (unpublished report). Dix, K.M., Van der Pauw, C.L. and McCarthy, W.V., (1975) Toxicity studies with dieldrin: Teratological studies in mice given HEOD orally. Tunstall Laboratory, Shell Research Ltd. TU/19/75. Submitted for publication in Teratology.. FAO/WHO (1971) 1970 Evaluations of some pesticide residues in food. AGP:1970/M/12/1;WHO/Food Add./71.42. Jager, K.W., (1970) Adrin, dieldrin, endrin and telodrin. An epidemiological and toxicological study of long-term occupational exposure. Thesis, 234 p., Elsevier Publ. Co., Amsterdam. Müller, W., Nohynek, G., Woods, G., Korte F. and Coulston, F., (1975a) Comparative metabolism of Dieldrin-14C in Mouse, Rat, Rabbit, Rhesus Monkey and Chimpanzee. Chemosphere 4, 89-92. Müller, W., Woods, G. Korte, F. and Coulston, F., (1975b) Metabolism and Organ Distribution of Dieldrin-14C in Rhesus Monkeys after single oral and intravenous administration. Chemosphere 4, 93-98. Ottolenghi, A.D., Haseman, J.K. and Suggs, F., (1974) Teratogenic effects of aldrin, dieldrin and endrin in hamsters and mice. Teratol. 9, 11-16 Van Raalte, H.G.S., (1977) Human experience with dieldrin. Accepted for publication in Ecotox. and Environm. Safety. Versteeg, J.P.J. and Jager, K.W., (1973) Long-term occupational exposure to the insecticides aldrin, dieldrin, endrin and telodrin. Brit. J. Ind. Med. 30, 201-202. Wright A.S., Akintouwa, D.A.A. and Wooder, M.F., (1977) Studies on the Interaction of Dieldrin with Mammalian Liver Cells at the Subcellular Level. Ecotox. and Environm. Safety 1, 7-16. Zelle, B. and Lohman P.H.M., (1977) Repair of DNA in cultured human cells treated with dieldrin and 4-nitroquinoline-N-oxide. Medical Biological Laboratory TNO report, September 1977 (unpublished report).
See Also: Toxicological Abbreviations Aldrin/dieldrin (WHO Pesticide Residues Series 4) Aldrin/dieldrin (WHO Pesticide Residues Series 5)