μg/dL and over are associated with adverse effects on sperm or semen and that BLLs of 20 μg/dL and over are associated with delayed conception time. Decreases in sperm count, density, and concentration were seen in men who had mean BLLs of 15-68 μg/dL. The NTP also concluded that there was sufficient evidence that maternal BLLs under 5 μg/dL are associated with reduced fetal growth or lower birth weight. There is limited evidence that maternal BLLs under 10 μg/dL are associated with preterm birth and spontaneous abortion. Prospective studies reviewed by the NTP provided limited evidence that prenatal exposure to BLLs under 10 μg/dL is associated with reduced postnatal growth in children. The NTP recognized that its conclusions about prenatal lead exposure were confounded by possible continuing postnatal exposure to lead (associated with BLLs under 10 μg/dL) that is also associated with reduced postnatal growth in children.

Other Studies Considered

Animal Toxicology Studies

The committee considered several key pieces of evidence derived from animal studies in its deliberations. Those studies identified effects on hormone function, gonad structure, and developmental (teratogenic) responses that have been incompletely examined in human epidemiologic investigations and provided additional weight of evidence that supports the committee’s conclusions.

In male rodents and monkeys, long-term lead exposure resulting in BLLs over 20 μg/dL reduced serum concentrations of luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol, and other reproductive hormones (Foster et al. 1993; Allouche et al. 2009; EPA 2012). Decreased reproductive-organ weight, histologic changes in the testes and germ cells, reduced fecundity, and decreased numbers of uterine and ovarian estrogen, luteinizing hormone, and follicle-stimulating hormone receptors occur in animals after lead exposure (Wiebe and Barr 1988; Wiebe et al. 1988; Singh et al. 1993; Batra et al. 2001; Wang et al. 2008; Anjum et al. 2011). Dumitrescu et al. (2008) demonstrated that exposure of female rats to lead at 150 ppb before mating and during pregnancy caused a concentration-dependent shift in the male-to-female sex ratio of the offspring, but this effect has not been replicated in other studies (Ronis et al. 1998).

Lead induces reproductive and developmental effects in laboratory rats after gestational or lactational exposure. Many of the effects occur in a concentration-dependent manner and have been observed at maternal BLLs that do not result in overt maternal toxicity (under 40 μg/dL). Animal studies have further demonstrated that effects of lead exposure during early development include impairment of retinal development and alterations in the developing hematopoietic and hepatic systems. Toxicology studies in male animals have reported delayed



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