PRINCIPLES OF TOXICOLOGY

236 REPRODUCTIVE TOXICOLOGY
Two important areas for additional investigation are: 1) developing better tools for investigating
human cognitive function and abilities and 2) characterizing the relationship between the doseresponse
characteristics of experimental animals and that of humans for lead. These questions are
important in terms of both public health and economics. In general, the scientific and regulatory
communities have regarded the clear and dramatic drop in children’s blood lead levels since the 1970s
as a real public health improvement realized through the control of lead from gasoline and paints. If
neurocognitive development turns out to be as sensitive as some suggest to the effects of lead, much
tougher questions about whether and how to address exposures, down to the range associated with
naturally occurring lead, will be up for consideration. Without obvious and readily replaceable major
exposure sources, like gasoline or paint, the costs associated with additional incremental reductions
in lead exposure for the population as a whole may be dramatic.
11.5 SUMMARY
This chapter has outlined the toxic responses of the male and female reproductive systems and the
developing fetus. Some of the mechanisms of toxicity, generally described using experimental
toxicants, have been presented to illustrate the types of responses and effects that should be considered.
In most cases, however, the experimental toxicants have limited direct application to human health
effects. Especially for occupational exposures, the gap between toxic potential and demonstrated
effects is large. Examples of actual human reproductive and developmental toxicants have been pointed
out so that those chemicals, which are currently known to represent a risk to humans, can be identified.
Some of the key points in the chapter included:
• The differential sensitivity of various tissues and cell types in the male and female reproductive
organs to certain types of toxicants.
• The functional and toxicological implications of the different patterns of cellular division
and germ cell maturation used by males and females.
• The multiple interactions between the reproductive and endocrine systems and the balance
of endocrine regulation that may be vulnerable during certain toxic responses.
• The relationship of the sequential course of developmental processes to toxic responses.
• The major difference in toxic responses between the embryonic and fetal periods of
development.
REFERENCES AND SUGGESTED READING
Alvarez, J. G., and B. T. Storey, “ Evidence for increased lipid peroxidative damage and loss of superoxide dismutase
as a mode of sublethal damage to human sperm during cryopreservation.” Jo. of Androl. 13: 232–241 (1992).
Arnold, S. F., D. M. Klotz, B. M. Collins, P. M. Vonier, L. J. Jr., Guillette, and J. A. McLachlan, Synergistic activation
of estrogen receptor with combinations of environmental chemicals [see comments] [retracted by McLachlan
JA. In: Science 1997 Jul 25; 277(5325):462–463], Science, 1996; 272: 1489–1492.
Ashby, J., J. Odum, H. Tinwell, and P. A. Lefevre, “Assessing the risks of adverse endocrine-mediated effects:
where to from here?” Regulatory Toxicology and Pharmacology 26: 80–93 (1997).
Ashby, J., H. Tinwell, P. A. Lefevre, J. Odum, D. Paton, S. W. Millward, S. Tittensor, and A. N. Brooks, “Normal
sexual development of rats exposed to butyl benzyl phthalate from conception to weaning.” Regulatory
Toxicology and Pharmacology 26(1 Pt 1):102–118 (1997).
Auger, J., J. M. Kunstmann, F. Czyglik, and P. Jouannet, “Decline in semen quality among fertile men in Paris
during the past 50 years.” New England Journal of Medicine 332: 281–285 (1995).
Bromwich, P., J. Cohen, I. Stewart, and A. Walker, “Decline in sperm counts: and artefact or changed reference
range of ‘normal’?” British Medical Journal 309: 19–22 (1994).