Reproductive toxicity embryonic / fetal development

Chemicals that cross the placental barrier can act directly on the embryo/fetus, and it is likely that the majority of chemicals that cause developmental toxicity act in this way. Teratogenic chemicals are most likely to act directly on the fetus. Some chemicals cause maternal toxicity at high doses but interfere with embryonic or fetal development at lower doses, and these chemicals are of concern in reproductive toxicology. Many of the most widely recognized embiyotoxic or teratogenic chemicals are selectively active in this manner, and the dose that causes developmental toxicity can be much lower than the dose that is toxic to the mother (Khera, 1984). 

Data to assess the potential of JP-8 to adversely affect reproduction and development are sparse. One study (Puhala et al. 1997) reported measurements of human exposures and the values for the components of jet fuels analyzed that were far below the TWA threshold limit values (see Tabel A-2). Data on the absorption of volatile hydrocarbon components of JP-8 suggest that systemic exposure is likely, by any route of exposure. The single published developmental toxicity study (Cooper and Mattie 1996) did not report an adverse effect on embryonic or fetal development in rats with oral treatment at up to 2,000 mg/kg/d on days 6-15 of pregnancy, except for a decrease in body weight of offspring. 

Any xenobiotic associated with adverse effects on development of male or female reproductive function can be classified as a reproductive toxicant (Evans, 2007 Rogers and Kavlock, 2008). Even chemicals adversely affecting animal well-being have a potential negative impact on development and reproductive function. This chapter will attempt to focus on toxicants which are available for or could arise from military and terrorist activities and specific mechanisms of actions which have a direct effect upon the male and/or female reproductive tract or which target normal embryonic and/or fetal growth and maturation (Evans, 2007). 

Figure 4 International Conference on Harmonisation guidelines on detection of toxicity to reproduction for medicinal products, (a) Study of fertility and early embryonic development (4.1.1) (b) study for effects on prenatal and postnatal development, including maternal function (4.1.2) (c) study for effects on embryo-fetal development (4.1.3) (d) single-study design (4.2) (e) two-study design (4.3).

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