Effects of respiratory treatment with N-hexane on rat testis morphology. I. A light microscopic study.

Testicular damage was induced in rats by respiratory treatment with n-hexane at a concentration of 5000 ppm. The earliest lesions were observed immediately after 24 hr of continuous treatment, and involved primary spermatocytes from the leptotene to the middle pachitene stages and spermatids at late stages of maturation; at the same time numerous exfoliated, injured germ cells reached the epididymis. After the 24-hr treatment was suspended, damage to the seminiferous epithelium increased for the first 7 days, while the epididymis showed also focal infiltration by inflammatory cells; recovery was completed from Days 14 to 30. Intermittent treatment (16 hr/day, 6 days/week) at the same concentration of 5000 ppm for up to 6 weeks induced progressive increases in testicular and epididymal lesions, which, after 5 weeks (when most animals began to show clinical symptoms of polyneuropathy), reached aplasia of the germinal epithelium involving also the spermatogonia. Recovery from clinical symptoms was not paralleled by a regression of testicular pathology. On the contrary, after interruption of the treatment, the testicular lesions became increasingly severe, up to complete atrophy of the seminiferous tubules, suggesting an irreversible sterility of the treated animals. Pair-fed controls did not show histological alterations of the testis or epididymis.

Urinary excretion of n-hexane metabolites. A comparative study in rat, rabbit and monkey.

Exposure to n-hexane, a component of many industrial solvent mixtures, is known to cause polyneuropathy in man. The concentration of metabolites in urine following exposure may be useful in biological monitoring. In a comparative study experimental animals (rat, rabbit and monkey) were subjected to single inhalatory treatments of 6, 12 and 24 h with 5,000 ppm of pure n-hexane. At the end of the treatments and at intervals thereafter, urine, and in rats also blood, were collected and analyzed for n-hexane and its metabolites. While the urine of rats contained 2-hexanol, 3-hexanol, methyl n-butyl ketone, 2,5-dimethylfuran, y-valerolactone and 2,5-hexanedione, rabbit and monkey urine were found to contain only 2-hexanedione, rabbit and monkey urine were to contain only 2-hexanol, 3-hexanol, methyl n-butyl ketone and 2,5-hexanedione. Within 72 h of the end of exposure, the principal metabolite was 2,5-dimethylfuran in rats and 2-hexanol in rabbits and monkeys. In all three species the excretion rates of methyl n-butyl ketone, 3-hexanol and 2-hexanol peaked several hours earlier than 2,5-hexanedione (and gamma-valerolactone and 2,5-dimethylfuran in rats). In all species 2,5-hexanedione was still detectable in urine 60 h following exposure. n-Hexane metabolites in rat blood were 2-hexanol, methyl-n-butyl ketone, 2,5-dimethylfuran and 2,4-hexanedione. The first two, as well as n-hexane itself, were found in maximum concentration immediately after termination of exposure, while 2,5-dimethylfuran and 2,5-hexanedione, with the longer exposure times, peaked some hours later. The data from urine collected at the end of exposure were compared with those obtained in a parallel study in humans occupationally exposed to a mixture of hexane isomers. Humans chronically exposed to 10-140 ppm n-hexane had 2,5-hexanedione concentrations in urine ranging from 0.4 to 21.7 mg/l, i.e., in the same proportion as rats exposed once for 6 or 12 h to 5,000 ppm.

Experimental neurotoxicity and urinary metabolites of the C5-C7 aliphatic hydrocarbons used as glue solvents in shoe manufacture.

Rats were intermittently exposed (9 to 10 h/d, 5 to 6 d/week) to controlled concentrations of single analytical grad solvents in ambient air. After periods ranging from 7 to 30 weeks the animals were perfused with glutaraldehyde and samples of nerves were processed for light microscopy of sections and of teased fibers. Animals treated with n-hexane at 5000 ppm (14 weeks) or 2500 ppm (30 weeks) developed the typical giant axonal degeneration already described in rats treated continuously with 400 to 600 ppm of the same solvent for 7 weeks or more. No such alterations were found in rats subjected to the following intermittent respiratory treatments: n-hexane 500 ppm (30 weeks) or 1500 ppm (14 weeks), cyclohexane 1500 or 2500 (30 weeks), n-pentane 3000 ppm (30 weeks), n-heptane 1500 ppm (30 weeks), 2-methylpentane 1500 ppm (14 weeks), and 3-methylpentane 1500 ppm (14 weeks). The following metabolites were found in the urine of rats according to treatment (in parenthesis): 2-methyl-2-pentanol (2-methylpentane); 3-methyl-2-pentanol and 3-methyl-3-pentanol (3-methylpentane), 2-hexanol, 3-hexanol, gamma-valerolactone, 2,5-dimethylfuran, and 2,5-hexanedione (n-hexane). 2-Hexanol was found to be the main urinary metabolite of n-hexane, while 2,5-hexanedione was present only in a lesser proportion. This feature of rat metabolism suggests that in this species 2,5-hexanedione reaches an effective level at its site of action during intermittent respiratory treatment with n-hexane with difficulty and explains the high concentrations necessary to cause polyneuropathy in rats subjected to this treatment.