Malformations, developmental

Developmental effects of trichloroethylene exposure have been demonstrated with the FETAX (Frog Embryo Teratogenesis Assay Xenopus) bioassay, an in vitro method using whole frog embryos (Fort et al. 1991, 1993 Rayburn et al. 1991). Observed defects included gut miscoding, skeletal kinking, and heart malformations heart malformations have also been observed in rat developmental assays (Dawson et al. 1993). 

Developmental Effects. Evidence from human studies on congenital anomalies as an end point (Emhart et al. 1985, 1986 McMichael et al. 1986 Needleman et al. 1984) indicate no association between prenatal exposure to low levels of lead and the occurrence of major congenital anomalies. This conclusion is further supported by developmental toxicity studies conducted in rats and mice these studies provide no evidence that lead compounds (acetate or nitrate) are teratogenic when exposure is by natural routes (i.e., inhalation, oral, dermal). Intravenous or intraperitoneal injection of lead compounds (acetate, chloride, or nitrate) into pregnant rats, mice, or hamsters, however, has produced malformations in several studies reviewed by EPA (1986a). 

Developmental Toxicity. Three human studies that described congenital malformations as an end point allow no definitive conclusion to be drawn regarding an association between prenatal lead exposure and the occurrence of congenital anomalies (Emhart et al. 1985, 1986 McMichael et al. 1986 ... 

Developmental Effects. There are no data available on developmental effects of acrylonitrile in humans however, two well-conducted studies in rats have shown that acrylonitrile is teratogenic in animals by both inhalation and oral exposure (Murray et al. 1978). Fetal malformations occurred in a dose-related manner. When administered orally, malformations were present even at doses in which no maternal or fetal toxicity was apparent. 

Up to 8% dead at dose range 0.01-1 mg As+5/embryo threshold for malformations at dose range 0.3-3 mg/embryo Teratogenic to embryos when injected at 1-2 mg/egg Developmental abnormalities at embryonic injected doses of 1-2 mg/egg... 

Among the most sensitive endpoints (on a body burden basis) are endometriosis, developmental neurobehavioural (cognitive) effects, hearing loss, developmental reproductive effects (sperm counts, female urinogenital malformations) and immuno-toxic effects, both adult and developmental. The most sensitive biochemical effects are CYP1A1/2 induction, hepatic retionid depletion, EGF-receptor down-regulation and oxidative stress. 

CD-I mouse resulted in slight maternal toxicity at 3,026 and 9,017 ppm and slight developmental toxicity (in the absence of malformations) at 9,017 ppm. 

Another possible use of in vitro developmental toxicity tests would be to select the least developmentally toxic backup from among a group of structurally related compounds with similar pharmacological activity [use (2) in the list above], for example, when a lead compound causes malformations in vivo and is also positive in a screen that is related to the type of malformation induced. However, even for this limited role for a developmental toxicity screen, it would probably also be desirable to have a measure of the comparative matemotoxicity of the various agents and/or information on the pharmacokinetics and distribution of the agents in vivo. 

Significant concentrations of cyanotoxins have been found to accumulate in the tissues of macroinvertebrates such as mollusks and crustaceans, presenting an indirect route of exposure for invertebrates, fish, and aquatic mammals at higher trophic levels (Negri and Jones 1995). In natural systems, mortality among benthic invertebrate herbivores is probably low because most bloom-forming bacteria are planktonic and only periodically come into contact with the benthos. Nevertheless, Kotak et al. (1996) determined that enhanced mortality of snails at the end of a bloom cycle in Canadian lakes was due to consumption of Microcystis cells that had formed a scum on the surface of macrophytes. Oberemm et al. (1999) found that aqueous microcystins, saxitoxins, and anatoxin-a all resulted in developmental delays in fish and salamander embryos. Interestingly, more severe malformations and enhanced mortality were observed when larvae were exposed to crude cyanobacterial extracts than to pure toxins applied at natural concentrations (Oberemm et al. 1999). 

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