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EXTOXNET PIP-DDT Page 3 of 6 administered on gestation days 4- resulted in decreased fetal weights and mg/kg/day on days 7-9 of gestation resulted in increased resorptions (73). In mice, doses of 1.67 mg/kg/day resulted in decreased embryo implantation and irregularities in the estrus cycle over 28 weeks (73). It is thought that many of these observed effects may be the result of disruptions in the endocrine (hormonal) system (73). Available epidemiological evidence from two studies does not indicate that reproductive effects have occurred in humans as a result of DDT exposure (73). No associations between maternal blood levels of DDT and miscarriage nor premature rupture of fetal membranes were observed in two separate studies (73, 77, 78). One study did report a significant association between maternal DDT blood levels and miscarriage, but the presence of other organochlorine chemicals(e.g., PCBs) in maternal blood which may have accounted for the effect make it impossible to attribute the effect to DDT and its metabolites (79). • Teratogenic Effects: There is evidence that DDT causes teratogenic effects in test animals as well. In mice, maternal doses of 26 mg/kg/day DDT from gestation through lactation resulted in impaired learning performance in maze tests (73). In a two-generational study of rats, 10 mg/kg/day resulted in abnormal tail development(73). Epidemiological evidence regarding the occurance of teratogenic effects as a result of DDT exposure are unavailable (73). It seems unlikely that teratogenic effects will occur in humans due to DDT at likely exposure levels. • Mutagenic Effects: The evidence for mutagenicity and genotoxicity is contradictory. In only 1 out of 11 mutagenicity assays in various cell cultures and organisms did DDT show positive results (73). Results of in vitro and in vivo genotoxocity assays for chromosomal aberrations indicated that DDT was genotoxic in 8 out of 12 cases, and weakly genotoxic in 1 case (73). In humans, blood cell cultures of men occupationally exposed to DDT showed an increase in chromosomal damage. In a separate study, significant increases in chromosomal damage were reported in workers who had direct and indirect occupational exposure to DDT (73). Thus it appears that DDT may have the potential to cause genotoxic effects in humans, but does not appear to be strongly mutagenic. It is unclear whether these effects may occur at exposure levels likely to be encountered by most people. • Carcinogenic Effects: The evidence regarding the carcinogenicity of DDT is equivocal. It has been shown to cause increased tumor production(mainly in the liver and lung) in test animals such as rats,mice and hamsters in some studies but not in others (73) In rats, liver tumors were induced in three separate studies at doses of 12.5 mg/kg/day over periods of 78 weeks to life, and thyroid tumors were induced at doses of 85 mg/kg/day over 78 weeks(73). In mice, lifetime doses of 0.4 mg/kg/day resulted in lung tumors in the second generation and leukemia in the third generation; liver tumors were induced at oral doses of 0.26 mg/kg/day in two separate studies over several generations. In hamsters, significant increases in adrenal gland tumors were seen at doses of 83 mg/kg/day in females (but not males) , and in males(but not females) at doses of 40 mg/kg/day (73). In other studies, however, no carcinogenic activity was observed in rats at doses less than 25 mg/kg/day; no carcinogenic activity was seen in mice with at doses of 3-23 mg/kg/day over an unspecified period, and in other hamster studies there have been no indications of carcinogenic effects(73). The available epidemiological evidence regarding DDTOs carcinogenicity in humans, when taken as a whole, does not suggest that DDT and its metabolites are carcinogenic in humans at likely dose levels (73). In several epimiological studies, no significant associations were seen between DDT exposure and disease,but in one other study, a weak association was observed (73, 80). In this latter study, which found a significant association between long-term, high DDT exposures and pancreatic cancers in chemical workers, there were questions raised as to the reliability of the medical records of a large proportion of the cancer cases (73,80). • Organ Toxicity: Acute human exposure data and animal studies reveal that DDT can affect the nervous system, liver, kidney (73). Increased tumor production in the liver and lung has been observed in test animals (73). An association with pancreatic cancer was suggested in humans in one study (73, 80). • Fate in Humans & Animals: DDT is very slowly transformed in animal systems (74). Initial degradates in mammalian systems are 1,1-dichloro-2,2-bis(p-dichlorodiphenyl)ethylene (DDE) and 1,1-dichloro-2,2-bis(p- chlorophenyl)ethane (DDD),which are very readily stored in fatty tissues (73). These compounds in turn are ultimately transformed into bis(dichlorodiphenyl) acetic acid (DDA) via other metabolites at a very slow rate (73). DDA, or conjugates of DDA, are readily excreted via the urine (73). Available data from analysis of human blood and fat tissue samples collected in the early 1970s showed detectable levels in all samples, but a downward trend in the levels over time (73). Later study of blood samples collected in the latter half of the 1970s showed that blood levels were declining further, but DDT or metabolites were still seen in a very high proportion of the