The compounds 2,4-dinitrotoluene (2,4-DNT) and 2,4-toluenediamine (2,4-TDA) are used widely, in the manufacture of polyurethane foams and industrial dyes. DNT is also used in the production of explosives, propellants, and in the synthesis of TDA. Evidence exists that 1) DNT is responsible for decreased spermatozoa, testicular atrophy, and epididymal degeneration in rodents and 2) TDA an in vivo metabolite in the male rat as well as a synthetic reduction product of DNT may be mutagenic. Preliminary studies carried out in our laboratories indicate that TDA exposure in male rats (at a dose comparable with 2.4-DNT) may result in decreased fertility and reduced fetal viability. The site(s) and mode(s) of action of these agents on the reproductive processes in the male rat are unknown. Increased circulating LH and testosterone levels appear to be related to the adverse reproductive effects of TDA and DNT in rats. (Preliminary findings). The present proposal aims to determine: 1) the effects of DNT on a) sperm number, b) weights of testes, seminal visicles, epididymides, and prostate glands, c) cellular architecture of the seminiferous tubules, and d) serum testosterone, LH and FSH concentrations in the male rat, 2) the order in which each endpoint is acted upon by DNT, 3) the effects of TDA in the male rat on a) sperm number b) weights of testes, seminal vesicles, epididymides, and prostate glands, c) serum testosterone, LH, and FSH concentrations d) integrity of the seminiferous tubules, and e) number of successful fertilizations with receptive females, and 4) the mutagenic and teratogenic effects in litters from male rats fed 2,4-TDA. The information derived from these studies is particularly important in view of the hitherto a) unknown reduced fertility effect of 2,4-TDA in rats and b) altered circulating LH and testosterone levels in male rats treated with DNT or TDA. The long range goals of this study are to improve 1) our understanding of the underlying factors responsible for impairment of reproductive function by DNT and TDA in the rat and 2) the ability to forecast the onset of germ cell damage by these agents. For example, if testicular or spermatozoa effects are secondary to alterations in LH, FSH or testosterone levels, the measurement of these hormones may be of value in predicting reproductive toxicity by DNT or TDA, and thereby avoid permanent gonadal lesions by continued exposure to these agents.
| Varma, S K; Bloch, E; Gondos, B et al. (1988) Reproductive toxicity of 2,4-toluenediamine in the rat. 3. Effects on androgen-binding protein levels, selected seminiferous tubule characteristics, and spermatogenesis. J Toxicol Environ Health 25:435-51 |
