Metabolism and testicular toxicity of 1,3-dinitrobenzene in rats of different ages. 1994

C D Brown, and C L Forman, and S F McEuen, and M G Miller
Department of Environmental Toxicology, University of California, Davis 95616-8588.

Susceptibility to 1,3-dinitrobenzene (1,3-DNB)-induced testicular damage is known to increase with age. The present study investigated the possibility that age-dependent differences in metabolism and disposition could account for differences in toxicity. [14C]1,3-DNB (25 mg/kg, ip) was administered to Sprague-Dawley rats which were 31, 75, or 120 days of age. Levels of 1,3-DNB and 1,3-DNB metabolites were determined in blood and urine. As animal age increased, peak blood concentrations of 1,3-DNB were lower and declined more slowly indicating an age-dependent decrease in rate of metabolism and a possible increase in volume of distribution. In younger animals, faster elimination rates were associated with higher blood levels of metabolites. Urinary metabolites were generally similar for all age groups with the exception of the diacetamidobenzene metabolite which was significantly lower in the urine of 31 days old rats. There were clear differences in the toxicokinetic profile for 1,3-DNB between the 31 day old rats and the other two age groups. However, differences between the 75 and 120 day old animals were less marked. Testicular damage induced by 1,3-DNB (25 mg/kg, ip) was hardly detectable in the youngest animals, while the intermediate age group showed a moderate lesion particularly in later stages of spermatogenesis. For the oldest animals, testicular damage was more severe, particularly in the earlier stages of spermatogenesis. Overall, the rapid elimination rate could account for the lack of 1,3-DNB toxicity in very young animals. However, simple metabolic differences were less likely to adequately explain the increase in testicular damage found as animal age increased from 75 to 120 days.

UI MeSH Term Description Entries
D008297 Male Males
D004136 Dinitrobenzenes Benzene derivatives which are substituted with two nitro groups in the ortho, meta or para positions. Dinitrobenzene,Dinitrophenyl Compound,Dinitrophenyl Compounds,Dinitrotoluene,Dinitrotoluenes,Compound, Dinitrophenyl
D000367 Age Factors Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time. Age Reporting,Age Factor,Factor, Age,Factors, Age
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013737 Testis The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS. Testicles,Testes,Testicle
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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