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EXTOXNET PIP - DDT Page 2 of 5 200 mg/kg. Single administrations of low doses to developing 10-day old mice are reported to have caused subtle effects on their neurological development(73). DDT is slightly to practically non-toxic to test animals via the dermal route, with reported dermal LD50s of 2,500-3,000 mg/kg in female rats (79, 73), 1000 in guinea pigs (73) and 300 in rabbits (73). It is not readily absorbed through the skin unless it is in solution(73). It is thought that inhalation exposure to DDT will not result in significant absorption through the lung alveoli (tiny gas-exchange sacs) but rather that it is probably trapped in mucous secretions and swallowed by exposed individuals following the tracheo-bronchial clearance of secretions by the cilia (73). Acute effects likely in humans due to low to moderate exposure may include nausea, diarrhea, increased liver enzyme activity, irritation (of the eyes, nose or throat), disturbed gait, malaise and excitability; at higher doses, tremors and convulsions are possible (73, 76). While adults appear to tolerate moderate to high ingested doses of up to 280 mg/kg, a case of fatal poisoning was seen in a child who ingested one ounce of a 5% DDT:kerosene solution (73). . Chronic Toxicity: DDT has caused chronic effects on the nervous system, liver, kidneys,and immune systems in experimental animals (73, 74). Effects on the nervous system observed in test animals include: tremors in rats at doses of 16-32 mg/kg/day over.26 weeks; tremors in mice at doses of 6.5-13mg/kg/day over 80-140 weeks; changes in cellular chemistry in the central nervous system of monkeys at doses of 10 f mg/kg/day over 100 days, and loss of equilibrium in monkeys at doses of 50 mg/kg/day for up to 6 months I (73). The main effect on the liver seen in animal studies was localized liver damage. This effect was seen in rats given 3.75 mg/kg/day over 36 weeks, rats exposed to 5 mg/kg/day over 2 years and dogs at doses of 80 mg/kg/day over the course of 39 months (73). In many cases lower doses produced subtle changes in liver cell physiology, and in some cases higher doses produced more severe effects (73). In mice doses of 8.33 mg/kg/day over 28 days caused increased liver weight and increased liver enzyme activity (73). Liver enzymes are commonly involved in detoxification of foreign compounds, so it is unclear whether increased liver enzyme activity in itself would constitute an adverse effect. In some species (monkeys and hamsters), doses as high as 8-20 mg/kg/day caused no observed adverse effects over exposure periods as long as 3.5-7 y years (73). Kidney effects observed in animal studies include adrenal gland hemorrhage in dogs at doses of 138.5 mg/kg/day over 10 days and adrenal gland damage at 50 mg/kg day over 150 days in dogs (73). Kidney damage was also seen in rats at doses of 10 mg/kg/day over 27 months (73). Immunological effects observed in test animals include: reduced antibody formation in mice following administration of 13 mg/kg/day for 3- 12 weeks and reduced levels of immune cells in rats at doses of 1 mg/kg/day (73). No immune system effects were observed in mice at doses of 6.5 mg/kg/day for 3-12 weeks (73). Dose levels at which effects were observed in test animals are very much higher than those which may be typically encountered by humans (74). The most significant source of exposure to individuals in the United States is occupational, occurring only to those who work or worked in the production or formulation of DDT products for export (75). Analysis of U. S' market basket surveys showed approximately a 30-fold decrease in detected levels of DDT and metabolites in foodstuffs from 1969-1974, and another threefold drop from 1975-1981, with a final estimated daily dose ' of approximately 0.002 mg/person/day (73). Based on a standard 70-kg person, this results in a daily intake of approximately 0.00003 mg/kg/day. Due to the persistence of DDT and its metabolites in the environment, very low levels may continue to be detected in foodstuffs grown in some areas of prior use (73). It has been suggested that, depending on patterns of international DDT use and trade, it is possible that dietary exposure levels may actually increase over time (73). Persons eating fish contaminated with DDT or metabolites may also be exposed via bioaccumulation of the compound in fish(73). Even though current dietary levels are quite low, past and current exposures may result in measurable body burdens due to its persistence in the body (73). More information on the metabolism and storage of DDT and its metabolites in mammalian systems is provided below (Fate in Humans and Animals). Adverse effects on the liver, kidney and immune system due to DDT exposure have not been demonstrated in humans in any of the studies which have been conducted to date (73). . Reproductive Effects; There is evidence that DDT causes reproductive effects in test animals. No reproductive effects were observed in rats at doses of 38 mg/kg/day administered at days 15-19 of gestation (73). In another study in rats, oral doses of 7.5 mg/kg/day for 36 weeks resulted in sterility (73). In rabbits, doses of 1 mg/kg/day administered on gestation days 4-7 resulted in decreased fetal weights and 10 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,