PRINCIPLES OF TOXICOLOGY

218 REPRODUCTIVE TOXICOLOGY
TABLE 11.1 Suspected Human Male Reproductive Toxicants
Industrial/Environmental Pharmaceutical Agents and Drugs
Cadmium Adriamycin
Carbon disulfide Busulfan
Chlordecone Chlorambucil
Dibromochloropropane (DBCP) Chlorpromazine
DDT Clonidine
Diethylhexyl phthalate Cyclophosphamide
Dinitrobenzene Diazepam
Epichlorohydrin Ethanol
Ethylene dibromide Guanethidine
Ethylene oxide Methotrexate
n-Hexane Methyl DOPA
2-Hexanedione Opiates
Ionizing radiation Propanolol
Lead Tetrahydrocannabinol
Mercury Vincristine
2-MethoxyethanolVinblastine
Tri-o-cresylphosphate
have been relatively few instances of occupational exposure leading to demonstrable decreases in male
fertility.
Cell type susceptibility to toxic injury can be roughly generalized with germ cells as the most
sensitive, followed by Sertoli cells and then Leydig cells. The hierarchical regulation of spermatogenesis
underlies this since development of germ cells is often affected by toxicants acting on the Sertoli
and Leydig cells. In turn, Sertoli cells are often affected by both Sertoli cell and Leydig cell-specific
toxicants. In addition, there need not be any specific site within the testis targeted by a reproductive
toxicant. Reproductive function is susceptible to agents that interfere with the central nervous system
and autonomic nervous function because of the importance of neuroendocrine regulation.
11.2 FEMALE REPRODUCTIVE TOXICOLOGY
For the sake of this chapter, female reproductive toxicology will only include toxic responses of mature
females not directly affecting the fertilized egg or subsequent development. All post-fertilization
toxicity relating to the developing offspring will be considered developmental toxicology (see Section
11.3). With this limitation, female reproductive function can be described by the same characteristics
outlined for the male—the key features being the production of female germ cells, eggs, and transport
of the germ cells, in this case the sperm and eggs, to the site of fertilization.
With reference to human occupational and environmental exposures, substantially less is known
about female-specific toxicology compared to male or developmental toxicology. One of the reasons
is that reproductive impairment of human females is difficult to both establish and analyze. Unless
there is an observed prolonged inability to maintain a pregnancy there is often little reason to investigate
whether toxic responses may have affected female reproductive function. While this may also be true
of occupationally exposed men as well, fast and fairly sensitive means to test the reproductive capacity
of men are available. Semen samples are easily obtained and evaluated, and, while such analysis cannot
definitively determine fertility, abnormalities are obviously a sign of a potential problem. On the other
hand, germ cell production by women is very difficult to monitor and potential indicators, such as
failure to menstruate or irregular menstruation, occur frequently enough and for such a variety of