Fetal sensitivity

A developing fetus is much smaller than an adult or even young child. The effects of chemical exposure are, therefore, much greater for the fetus. An exposure of 10 ppb of PCBs will have a negligible effect on an adult but will impair the brain development of a fetus. 

The fetus has an immature, porous blood-brain barrier, allowing greater exposures to the developing brain. 

The fetus has lower levels of some chemical-bonding proteins, allowing a greater accessibility to target organs. 

The developing fetus organs are rapidly developing and are most vulnerable to toxic attack than fully developed organs. 

In the fetus, the systems and organs that detoxify and excrete toxic chemicals are not fully developed. This leads to longer residence times and correspondingly greater toxic effects. 

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Khera KS (1984) Adverse effects in humans and animals of prenatal exposure to selected therapeutic drugs and estimation of embryo-fetal sensitivity of animals forhuman risk assessment A review. In Kalter H ed. Issues and reviews in teratology, Vol. 2. New York, Plenum Press, pp 399-508. 

Cord-blood Hg measurement cannot show temporal variability in exposure. It can provide data on a limited portion of gestation whose duration is somewhat uncertain but which occurs late in gestation. That portion of gestation might not correspond to the periods of greatest fetal sensitivity to MeHg neurotoxicity. 

Other toxicological effects that may be associated with exposure to benzyl chloride based on animal studies are skin sensitization and developmental embryo and/or fetal toxicity. A 1980 OSHA regulation has estabhshed a national occupational exposure limit for benzyl chloride of 5 mg/m (1 ppm). Concentrations of 160 mg/m (32 ppm) in air cause severe irritation of the eyes and respiratory tract (68). 

The data from the only available animal study (Prigge and Greve 1977) indicate that inhaled lead is not teratogenic. However, it impaired heme synthesis in both rat dams and fetuses. In this study, dams were exposed to 1, 3, or 10 mg lead/m3 (chemical species not provided) throughout gestation (days 1-21). Maternal and fetal ALAD were inhibited at all exposure levels in a dose-related manner, and fetal (but not maternal) hematocrit and body weight were decreased at the 10-mg/m3 lead level. These results suggest that the fetuses were more sensitive to lead-induced toxicity than were the dams. 

Adverse effects of copper deficiency can be documented in terrestrial plants and invertebrates, poultry, small laboratory animals, livestock — especially ruminants — and humans. Data are scarce or missing on copper deficiency effects in aquatic plants and animals and in avian and mammalian wildlife. Copper deficiency in sheep, the most sensitive ruminant mammal, is associated with depressed growth, bone disorders, depigmentation of hair or wool, abnormal wool growth, fetal death and resorption, depressed estrous, heart failure, cardiovascular defects, gastrointestinal disturbances, swayback, pathologic lesions, and degeneration of the motor tracts of the spinal cord (NAS 1977). 

A1 Rat fetal intestinal epithelial cells Temperature-sensitive differentiation More suited to study paracellular transport (leakier pores) than Caco-2... 

Other cell lines used in permeability studies include the T84 human colonic adenocarcinoma colonic crypt cell model. This line has a reduced carrier expression, secrets mucus, and has very high resistance [31, 32], The IEC cell line is a rat fetal intestinal epithelium cell with higher permeabilities than Caco-2 cells [33], LLC PKi is a pig kidney epithelial cell line with low expression of efflux systems, but expression systems for transport proteins [32], 2/4/A1 cells are a conditionally immortalized rat fetal intestinal epithelium line with crypt cell-like morphology and temperature-sensitive differentiation [34], They form differentiated monolayers with tight junctions, increased brush border enzymes when grown on extracellular matrices with laminin. Transport of drugs with LP in 2/4/A1 monolayers was comparable to that in the human jejunum and up to 300 times faster than that in Caco-2 monolayers. In contrast, the permeability of HP drugs was comparable in both cell lines [34],... 

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