Perinatal studies

Animal toxicology a summary along with acute, long-term, reproduction, local toxicity and mutagenic/carcinogenic data. There are detailed requirements of toxicity studies in terms of time, dose, route of administration, which are beyond the scope of this article. Reproduction study requirements are also specified in terms of fertility studies, terato-genecity studies and perinatal studies. Local toxicity is limited to preparations intended for topical use. 

Adverse kidney effects have been reported in rats exposed to lead during development (Fowler et al. 1980). Also, alterations in immune function have been observed in young rats exposed to lead perinatally (Faith et al. 1979 Luster et al. 1978). These studies are discussed in more detail in Sections 2.2.3.2 and 2.2.3.3. 

Van Loveren, H. et al., Immunotoxicological consequences of perinatal chemical exposures a plea for inclusion of immune parameters in reproduction studies, Toxicology, 185, 185, 2003. 

Silverstein FS, Naik B. 1991. Effect of depolarization on striatal amino acid efflux in perinatal rats an in vivo microdialysis study. Neurosci Lett 128(1) 133-136. 

Heptachlor epoxide was measured in a strip of skin, fat, and subcutaneous tissue from 68 children who died in the perinatal period and ranged from not detected (nondetectable) to 0.563 ppm (mean 0.173) (Zavon et al. 1969). In 10 other stillborn infants, heptachlor epoxide levels measured in various tissues were as follows brain (nondetectable), lung (0.17 0.07 ppm), adipose (0.32 0.10 ppm), spleen (0.35 0.08 ppm), liver (0.68 0.50 ppm), kidney (0.70 0.28 ppm), adrenal (0.73 0.27 ppm), and heart (0.80 0.30 ppm) (Curley et al. 1969). In another study, the following heptachlor epoxide levels were measured in extracted lipids from mothers and newborn infants maternal adipose tissue (0.28 0.31 ppm), maternal blood (0.28 0.46 ppm), uterine muscle (0.49 0.51 ppm), fetal blood (1.00 0.95 ppm), placenta (0.50 0.40 ppm), and amniotic fluid (0.67 1.16 ppm) (Polishuk et al. 1977a). These data provide evidence of transplacental transfer to the fetus. 

Gd 0-19 and postnatal days 5-27 males were exposed throughout the study. Fj and F2 pup body weights in the 538 ppm group were significantly reduced from postnatal day 0 to 28. The number of Fj and F2 pups that died during the perinatal period was significantly elevated in the 538 ppm group (Tyl and Neeper-Bradley 1989). 

A recent study confirmed that ethylene thiourea was carcinogenic in male and female rats as shown by increased incidences of thyroid follicular cell neoplasms after treatment of up to 250 ppm in the diet for 2 years. In mice, concentrations ranging from 100 to 1000 ppm for 2 years caused liver and pituitary tumors in addition to thyroid tumors. Perinatal exposure up to 8 weeks followed by a control diet for 2 years was not carcinogenic in rats or mice. Combined perinatal-adult ETU exposures produced the same carcinogenic effects as adult-only exposures. 

Children Zidovudine has been studied in HIV-infected pediatric patients over 3 months of age who had HIV-related symptoms or who were asymptomatic with abnormal laboratory values indicating significant HIV-related immunosuppression. Zidovudine also has been studied in neonates perinatally exposed to HIV. 

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