The stability of aqueous solutions of organic N-chloramines, suspected of contaminating chlorinated water, has been studied. Two factors influence the decomposition of solutions of N-chloropiperidine and N-chlorodiethylamine: a spontaneous decomposition and photodecomposition. Since solutions of these compounds are relatively long-lived, a need for an analytical method for their identification is discussed. A new method is described which involves reaction of organic N-chloramines with arenesulfinic acid salts. The method gives high yields of stable arenesulfonamides. Several toxicological studies ofN-chloropiperidine are described. The compound is mutagenic by Ames assay in Salmonella typhimurium strain TA 100 and does not require metabolic activation as indicated in a total body fluids analysis using C57BL/J6 mice. N-Chloropiperidine was subjected to a modified in vitro cell transformation assay using diploid fibroblast cells from Syrian hamster fetuses. A maximum number of foci of 4 per dish was observed at a seeding of 5 x 103 cells/60 mm dish. Under similar conditions, MNNG-induced foci ranged from 4 to 7 per dish.

The stability of aqueous solutions of organic N-chloramines, suspected of contaminating chlorinated water, has been studied. Two factors influence the decomposition of solutions of N-chloropiperidine and N-chlorodiethylamine: a spontaneous decomposition and photodecomposition. Since solutions of these compounds are relatively long-lived, a need for an analytical method for their identification is discussed. A new method is described which involves reaction of organic N-chloramines with arenesulfinic acid salts. The method gives high yields of stable arenesulfonamides. Several toxicological studies ofN-chloropiperidine are described. The compound is mutagenic by Ames assay in Salmonella typhimurium strain TA 100 and does not require metabolic activation as indicated in a total body fluids analysis using C57BL/J6 mice. N-Chloropiperidine was subjected to a modified in vitro cell transformation assay using diploid fibroblast cells from Syrian hamster fetuses. A maximum number of foci of 4 per dish was observed at a seeding of 5 x 103 cells/60 mm dish. Under similar conditions, MNNG-induced foci ranged from 4 to 7 per dish.

Induction of sperm abnormality in mice and hamster and reproductive toxicity in mice was examined following chronic exposures (ad libitum) to N-chloropiperidine (NCP). The results showed that significant levels of abnormal sperm in the NCP treated group were observed after five weeks of exposure. The time of the appearance of NCP-induced anomalous sperm suggested that the compound did not affect late spermatocytes and spermiogenesis. Reproductive toxicological analysis based on moles, implantations, and offspring per pregnancy revealed that while the toxic effect of ethylmethane sulfonate was evident within the first week of treatment, NCP-induced toxicity was observed only after five weeks of treatment. The data further showed that in matings where both parents were exposed to NCP, the frequencies of moles, implantations, and offspring per pregnancy were fewer than those observed in single parent exposure.

The effects of 1,3-diphenylguanidine (DPG) on seminal cytology in hybrid mice and inbred Syrian golden hamsters and on testicular histology and reproductive toxicity in mice were monitored. Treatment consisted of chronic exposure of hamsters and mice to DPG in 0.025% acetic acid ad libitum. Sperm morphology and sperm count, testicular cytology and histology, and reproductive toxicity were monitored 1 wk after exposure. The results show that DPG induces (1) time- and dose-dependent morphologically anomalous sperm in mice and hamsters; (2) significant decreases in sperm count and testicular weight; (3) irregularly shaped seminiferous tubules characterized by the absence of a defined basement membrane, loss of interstitial cells, and limited number of spermatids and spermatozoa in the lumen of the tubules; and (4) reduced fertility indices, implants per pregnancy, and fetal mortality in mice. The coincidence of increased morphologically anomalous sperm and drastic reductions in fertility indices and implants per pregnancy is suggestive of developmental disturbances in the preleptotene and late-spermatogonial cells (5-7 wk after treatment).

Daunomycin interferes with the meiotic cycle and structural integrity of chromosmes if administered to microsporocytes of Vicia faba during the meiotic prophase substages prior to diplotene. The principal cytological consequences of daunomycin treatment are as follows: induced achromatic lesions, chromosome fragmentation, terminal and interstitial deletions, loose or non-pairing regions, multivalent associations, reduced chromosome condensation, chromosome stickiness, dicentric and side-arm bridges and chromatid loops. A correlation between inhibition of DNA or RNA and the cytological manifestation of structural anomalies or unfolding of meiotic events is discussed.