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Toxicological Sciences 54, 416-423 (2000)
Copyright © 2000 by the Society of Toxicology

Reproductive Toxicity of 1-Bromopropane, a Newly Introduced Alternative to Ozone Layer Depleting Solvents, in Male Rats

Gaku Ichihara*,1, Xiaozhong Yu{dagger}, Junzoh Kitoh{ddagger}, Nobuyuki Asaeda§, Toshihiko Kumazawa§, Hisakazu Iwai§, Eiji Shibata, Tetsuya Yamada*, Hailan Wang*, Zhenlin Xie*, Kei-ichiro Maeda||, Hiroko Tsukamura|| and Yasuhiro Takeuchi*

* Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan; {dagger} National Institute of Industrial Health, Kanagawa, Japan; {ddagger} Institute for Laboratory Animal Experiments, Nagoya University School of Medicine, Nagoya, Japan; § Safety Assessment Laboratory, Sanwa Kagaku Kenkyusho Co. Ltd., Mie, Japan; Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya, Japan; and || Nagoya University Graduate School of Bioagricultural Sciences, Nagoya, Japan

1-Bromopropane has been newly introduced as an alternative to ozone-depleting solvents. We aimed to clarify its dose-dependent reproductive toxicity in male rats. Thirty-six Wistar male rats were randomly divided into 4 groups of 9. The groups were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 12 weeks. Epididymal sperm indices were evaluated after a 12-week exposure. The testes, epididymides, seminal vesicle, prostate, and other organs were weighed and examined histopathologically. Spermatogenic cells, in stage VII seminiferous tubules, and retained spermatids, at the basal region of stages IX–XI seminiferous epithelium, were counted. Plasma testosterone levels were measured by radioimmunoassay. The testicular weight did not significantly change, but the weight of epididymides, seminal vesicle, and prostate dose-dependently decreased. The weight of seminal vesicle decreased significantly at the lowest concentration of 200-ppm and over. 1-Bromopropane induced a dose-dependent decrease in the epididymal sperm count and in motility, as well as an increase in tailless sperm and sperm with an immature head shape. The spermatogonia, preleptotene spermatocytes, pachytene spermatocytes, and round spermatids did not decrease significantly at stage VII. Retained, elongated spermatids near the basement membrane at the postspermiation stages IX–XI increased dose-dependently. Plasma testosterone levels significantly decreased at the 800-ppm dosage. 1-Bromopropane caused failure of spermiation. Its reproductive toxicity is different from that of 2-bromopropane, which specifically impairs spermatogonia. Thus, this solvent may have serious reproductive toxic effects in men, and should be used very cautiously in the workplace.

Key Words: 1-bromopropane; reproductive toxicity; alternative to chlorofluorocarbons; spermiation failure; retention of elongated spermatid; spermiogenesis; Sertoli cell; testosterone; seminal vesicle; banana-like head.


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