Prenatal mortality

The prenatal developmental toxicity study design includes sacrifice of the rodent or rabbit dam one day prior to expected delivery, in order to ensure that malformed fetuses are not lost to maternal cannibalism. .. Nevertheless, even the prenatal developmental toxicity study does not allow the researcher to distinguish the source or cause of prenatal mortality. Intrauterine deaths may be the result of malformations that are incompatible with continuing viability... The contribution of malformed fetuses to overall effect on litter viability can be appropriately analysed by combining the litter incidence of conceptuses that are malformed, resorbed (early and late), and dead (full term but nonviable at caesarean section) and performing appropriate statistical analyses of group values (13). 

Sparschu et al. reported the embryotoxicity of TCDD in rats (1970) (refs. 122a,b). Data are summarized for rats and mice in Table 5. The three major effects observed were intestinal hemorrhages (rat fetuses) and increased incidence of cleft palate and kidney abnormalities (mouse fetuses). TCDD in pg/kg doses has also been reported to cause embryotoxic effects in hamsters eye abnormalities, reduction of mean fetal weight GI hemorrhages, increased prenatal mortality- (ref. 123). 

Some common developmental effects attributed to 2,3,7,8-TCDD exposure in most laboratory mammals are thymic hypoplasia, subcutaneous edema, decreased prenatal growth, and prenatal mortality (Couture et al. 1990). In addition, there are other species-specific effects, such as cleft palate in mice. Any of... 

Most of what is known about the toxicity of dioxins in the human comes from individuals exposed incidentally or chronically to higher levels (e.g., industrial accidents or presence in areas sprayed with Agent Orange or other herbicides contaminated with dioxins.). The lowest dose effects are probably associated with thymic atrophy and decreased immune response, chloracne and related skin lesions, and neoplasia (cancer). Dioxins can cross into the placenta to cause developmental and reproductive effects, decreased prenatal growth, and prenatal mortality. 

Future studies on the prenatal and developmental toxicology of arsenicals should consider deleterious effects in non-rodent species. Elucidation of chronic, low-level arsenicalism in relation to prenatal mortality and teratogenicity is an important step towards a more precise assessment of the possible hazard to humans and food-producing animals. The compounds should be given to the test animals by the same routes by which the target species are exposed, primarily by inhalation and in the drinking water. Attention should be paid to not only the concentration of total arsenic in maternal and embryonic tissues associated with the induction of prenatal toxicity, but to the concentrations and toxicokinetics of the various chemical species. 

Nickel Ni Growth reduction Impaired reproduction prenatal mortality (in animals) Lung cancer contact dermatitis, mostly in women Nickel may replace other metals in their ordinary sites in enzymes... 

An increase in the frequency of runts and a greater prenatal and neonatal mortality were found in rats chronically exposed to nickel chloride or nickel sulphate in food or drinking water [423, 424]. When rats were given single (10-30 mg/kg) and repeated (2mg/kg) intramuscular injections of nickel chloride on days 8 or 18 and 6 to 10 of gestation, respectively, no malformations were found, but a reduction in the number of live pups was observed [297],... 

Trisomy 13 (Patau syndrome, 47,XY,+13 47,XX,H 13) is seen in approximately 1 in 10,000 live births. More than 90% of conceptions are lost prenatally, and more than 90% of those who survive to term do not survive to 1 year of age. Common disease features include oral-facial clefts, microphthalmia (small eyes), renal defects, and polydactyly (extra fingers). Central nervous system malformations and heart defects are common and contribute to mortality. 

Prenatal glucocorticoid therapy to enhance fetal lung maturation reduces neonatal morbidity and mortality. However, adverse effects of serial courses of betamethasone on mother and fetus can occur. 

Summarizing, the main effects of. prenatal exposure to PCBs in the species studied were low birth weights, high peri- and postnatal mortalities and poor growth rates of the offspring. Exposure to PCBs very early in pregnancy could inhibit implantation. 

Nickel has been shown to adversely affect the blood (e.g., severe erythrocytosis) in experimental rats. Oral exposure to soluble nickel has been shown to cause increased prenatal or neonatal mortality. 

In contrast, mice lacking the p,-AR (PrAR-KO) have an increase in prenatal lethality between embryonic days 11 and 18.5, a time when cardiogenesis is complete and after initiation of the heartbeat (28). However, the penetrance of lethality in the PrAR-KO mice is strain dependent approx 90% of mice homozygous for the Pi-AR disruption die in utero between embryonic days 10.5 and 18.5, when the disruption is present on a 129-Sv congenic background. The mortality is still evident but reduced ( 70%) when the disruption is present on outbred backgrounds. Surviving pr AR-KO mice have structurally normal hearts. 

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