PRINCIPLES OF TOXICOLOGY - Biology East Borneo

218 REPRODUCTIVE TOXICOLOGYTABLE 11.1 Suspected Human Male Reproductive ToxicantsIndustrial/EnvironmentalPharmaceutical Agents and DrugsCadmiumAdriamycinCarbon disulfideBusulfanChlordeconeChlorambucilDibromochloropropane (DBCP) ChlorpromazineDDTClonidineDiethylhexyl phthalateCyclophosphamideDinitrobenzeneDiazepamEpichlorohydrinEthanolEthylene dibromideGuanethidineEthylene oxideMethotrexaten-HexaneMethyl DOPA2-HexanedioneOpiatesIonizing radiationPropanololLeadTetrahydrocannabinolMercuryVincristine2-MethoxyethanolVinblastineTri-o-cresylphosphatehave been relatively few instances of occupational exposure leading to demonstrable decreases in malefertility.Cell type susceptibility to toxic injury can be roughly generalized with germ cells as the mostsensitive, followed by Sertoli cells and then Leydig cells. The hierarchical regulation of spermatogenesisunderlies this since development of germ cells is often affected by toxicants acting on the Sertoliand Leydig cells. In turn, Sertoli cells are often affected by both Sertoli cell and Leydig cell-specifictoxicants. In addition, there need not be any specific site within the testis targeted by a reproductivetoxicant. Reproductive function is susceptible to agents that interfere with the central nervous systemand autonomic nervous function because of the importance of neuroendocrine regulation.11.2 FEMALE REPRODUCTIVE TOXICOLOGYFor the sake of this chapter, female reproductive toxicology will only include toxic responses of maturefemales not directly affecting the fertilized egg or subsequent development. All post-fertilizationtoxicity relating to the developing offspring will be considered developmental toxicology (see Section11.3). With this limitation, female reproductive function can be described by the same characteristicsoutlined for the male—the key features being the production of female germ cells, eggs, and transportof 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 knownabout female-specific toxicology compared to male or developmental toxicology. One of the reasonsis that reproductive impairment of human females is difficult to both establish and analyze. Unlessthere is an observed prolonged inability to maintain a pregnancy there is often little reason to investigatewhether toxic responses may have affected female reproductive function. While this may also be trueof occupationally exposed men as well, fast and fairly sensitive means to test the reproductive capacityof men are available. Semen samples are easily obtained and evaluated, and, while such analysis cannotdefinitively determine fertility, abnormalities are obviously a sign of a potential problem. On the otherhand, germ cell production by women is very difficult to monitor and potential indicators, such asfailure to menstruate or irregular menstruation, occur frequently enough and for such a variety of