The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
CONFIRMATION STUDY, USING NITROBENZENE, OF THE COMBINED REPEAT DOSE AND REPRODUCTIVE/DEVELOPMENTAL TOXICITY TEST PROTOCOL PROPOSED BY THE ORGANIZATION FOR ECONOMIC COOPERATION AND DEVELOPMENT (OECD)
Kunitoshi MITSUMORIYukio KODAMAOsayuki UCHIDAKoichi TAKADAMinoru SAITOKatsusi NAITOSatoru TANAKAYuji KUROKAWAMakoto USAMIKunio KAWASHIMAKazuo YASUHARAKazuhiro TOYODAHiroshi ONODERAFumio FURUKAWAMichihito TAKAHASHIYUZO HAYASHI
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Keywords: OECD guideline
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1994 Volume 19 Issue 3 Pages 141-149

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Abstract

A confirmatory familiarization study of the Combined Repeat Dose and Reproductive/Developmental Toxicity Screening (ReproTox) test protocol proposed by the Organization for Economic Cooperation and Development (OECD) was performed using nitrobenzene, a testicular toxicant. The agent was given daily by gavage to groups of 10 male and 10 female Sprague-Dawley rats at doses of 100, 60, 20 and 0 mg/kg body weight. Some of the high dose animals exhibited neurological signs, and two males and 9 females died. Hemolytic anemia due to methemoglobin formation was evident in treated males. Histopathologically, treated males showed atrophy of seminiferous tubules of the testis, reactive changes secondary to hemolytic anemia in the hematopoietic organs, and hepatocellular swelling. Cerebral gliosis was observed in middle and high dose males. Male fertility was not affected. The body weights of pups from treated dams were lowered, and their postnatal loss was increased. Most of the known toxicological properties of this chemical was demonstrated in the present study, with the exception of reduced fertility. Therefore, the ReproTox protocol was concluded as being useful as a screening test of existing high production volume chemicals. It should be noted that while the reproductive toxicity test alone is insensitive for detection of male fertility disturbances associated with testicular toxicity, the latter easily be distinguished on morphological grounds.

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