and storage. Lead-induced production of reactive oxygen species (ROS), calcium mimicry, and binding to protein sulfhydryl groups are potential biochemical modes of action (EPA 2012). And lead can alter zinc, iron, and potassium function in cells (Sun and Suszkiw 1994; Lal et al. 1996; Lasley and Gilbert 1996).

Pharmacokinetic modes of action warrant consideration. Lead is consistently detected in human testes, epididymides, prostate, and seminal vesicles (Oldereid et al. 1993). Of particular concern is the accumulation of lead in the epididymides because this results in long-term exposure of semen to lead. Lead enters human sperm (and probably related cells at earlier stages of differentiation) through voltage-gated potassium and calcium channels (Benoff et al. 2007). Different isoforms of those channels differ in their ability to transport lead, and expression of channel isoforms likewise differ among men. Exposure to a given BLL may therefore result in different intracellular lead concentrations in male germ cells and have different effects on fertility. Pregnant women can transfer lead to their fetuses, as demonstrated by the strong correlation between maternal and umbilical cord BLLs (Gardella 2001). During pregnancy and after birth, skeletal lead stores are an important contributor to maternal BLLs (Gulson et al. 1999). Lead levels in breast milk increase with increasing maternal BLL, and this poses an additional risk to the neonate (Li et al. 2000).

Conclusions from the 2012 Environmental Protection Agency and 2012 National Toxicology Program Lead Documents

Environmental Protection Agency 2012 Integrated Science Assessment for Lead (Second External Review Draft)

EPA’s review of recent epidemiologic studies of environmental lead exposure and reproductive function concludes that there is strong evidence that increasing lead exposure is associated with reduced male fecundity or fertility, decreases in sperm count, and reduced sperm velocity and motility. EPA’s draft report further concludes that deleterious associations with sperm count and quality are observed in occupationally exposed men who have mean BLLs as low as 20-45 μg/dL. EPA concluded that there was some association between maternal lead exposure and low birth weight; toxicologic studies in animals have shown that lead exposure during early fetal development can result in abnormal retinal development and alterations in the developing hematopoietic and hepatic systems.

National Toxicology Program 2012 Monograph on Effects of Low-Level Lead

The NTP concluded that there was inadequate evidence to conclude that BLLs under 10 μg/dL are associated with adverse effects on reproduction in men. There was, however, sufficient evidence to conclude that BLLs of 15



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement