Chronic inhalation exposure of adult rats to hexane causes neural toxicities to develop over a period of several weeks. Because the developing organism is in many cases more vulnerable to toxic insult than the adult, and children make up a substantial proportion of the population of solvent abusers, we compared the effects of exposing weanling and young adult rats to 1000 ppm of hexane for 24 hrs/day, 6 days/week, for 11 weeks. Within two weeks of exposure, significance decreases in body weight and grip strength were observed in rats of both ages. However, the subsequent effects of the treatment on these indices of toxicity were greater in the young adults than in the rats first exposed as weanlings. The older rats also exhibited earlier and more severe signs of hindlimb flaccid paralysis. In contrast, the effects of hexane on tail nerve conduction time and on the brainstem auditory-evoked response were about the same in rats of both ages, with latencies increasing compared to controls over the exposure period. The relative resistance of the weanling rats to hexane neuropathy may be due to shorter, smaller-diameter axons, or to a greater rate of growth and repair in their peripheral nerves compared to those of adults.

Action Potentials↗

PubMedDate not supplied

Hearing loss in rats first exposed to toluene as weanlings or as young adults.

Male Fischer-344 rats were exposed by inhalation to 1200 ppm toluene (14 hr/day, 7 days/week for 5 weeks) beginning just after weaning or as young adults. During the fifth week of exposure, they were trained to perform a multisensory conditioned pole-climb avoidance response (CAR) task using a 4-kHz tone, a change in the intensity of the test chamber light, or a nonaversive current on the grill floor as the stimuli. When tested the week after the exposures ended, both groups of toluene-exposed rats were deficient in their performance of the CAR to a 20-kHz tone. This effect was significantly greater for the rats exposed beginning just after weaning than it was for the young adult rats. Subsequent behavioral and electrophysiologic audiometry confirmed the presence of a toluene-induced high-frequency hearing loss in both groups of rats with the more severe deficits occurring in the younger rats. Preliminary morphologic examinations revealed loss of, and/or damage to, hair cells in the basal turn of the cochlea of the younger toluene-exposed rats. These results confirm our earlier discovery that inhalation exposure to toluene causes hearing deficits in rats, and they indicate that young, prepubertal rats are more severely affected than older rats.

Age Factors↗

PubMedDate not supplied

Factors affecting toluene-induced ototoxicity in rats.

Seven experiments with young male Fischer rats were done to examine concentration and exposure parameters necessary and sufficient to cause toluene-induced ototoxicity. Hearing loss, measured by behavioral and electrophysiologic methods, was repeatedly observed after as few as 2 weeks of exposure to 1000 ppm toluene for 14 hours per day, but lower concentrations (400 and 700 ppm) were without effect even after 16 weeks of exposure. Three-day exposures to 1500 ppm for 14 hours per day or 2000 ppm for 8 hours per day were ototoxic, whereas single exposures to 4000 ppm for 4 hours or 2000 ppm for 8 hours were without effect. Intermittent exposure to 3000 ppm for 30 minutes every hour for 8 hours per day caused hearing loss within 2 weeks, but a similar exposure schedule for 4 hours per day was ineffective even after 9 weeks. The results of these experiments repeatedly confirmed our earlier finding that toluene causes hearing loss in rats and defined many of the exposure parameters important to this effect. The results are discussed in terms of their relevance to industrial exposure, industrial accidents, and, especially, voluntary, high-level exposure by solvent abusers.

Animals↗

PubMedDate not supplied

Transient cognitive deficits and high-frequency hearing loss in weanling rats exposed to toluene.

In a previous experiment we found that weanling rats subchronically exposed to toluene by inhalation were deficient in learning a multisensory conditioned avoidance response (CAR) task and a tone-intensity discrimination task when trained several hours after each daily 14-hour exposure ended. The present experiment was done to determine whether this deficit represented a residual pharmacologic effect or more persisting nervous system damage. Independent groups of rats were trained on the CAR task either during the last week of a 5-week exposure to 1400 or to 1200 pm toluene (14 hr/day, 7 days/week) or during the first or third weeks after the exposures ended. None of the three groups of toluene-exposed rats were able to acquire the auditory CAR, whereas it had been 4 kHz in the previous experiment. Subsequent tests, in which the frequency and intensity of the tone were varied, revealed that hearing in these rats was unimpaired at 4 kHz, slightly impaired at 8 kHz, and markedly impaired at 12 kHz and above. Thus, although toluene has been shown to be relatively innocuous as a toxicant, this new finding suggests that this solvent should be examined further in terms of its potential hazard, especially with regard to its frequent abuse.

Animals↗

PubMedDate not supplied

Neurobehavioral effects of subchronic exposure of weanling rats to toluene or hexane.

Using several behavioral and neurophysiologic tests, we examined the effects of subchronic inhalation exposure of rats to toluene and compared them with the effects of the known neurotoxicant hexane. The rats were exposed to toluene (900 and 1400 ppm) or hexane (2000 ppm) 14 hr/day, 7 days/week for 14 weeks. Both solvents inhibited weight gain. Hexane caused a neurotoxic syndrome characterized by reductions of grip strength (especially hindlimb), motor activity, and startle responses, and increased latencies of several evoked potential components. Initial acquisition of a conditioned avoidance response (CAR) was also impaired, but subsequent performance was intact. Toluene did not cause the peripheral motor symptoms associated with exposure to hexane. However, a component of the brainstem auditory-evoked response was depressed and CAR acquisition was impaired along with the acquisition of a tone-intensity discrimination task when tested within hours after the daily exposure ended.

Action Potentials↗

PubMedDate not supplied

Drinking behaviour among Saskatchewan adolescents.

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Adolescent↗

PubMedDate not supplied

Importance of schedule of exposure to hexane in causing neurotoxicity.

Male Fischer rats exposed continuously (24 hr per day) to 1,000 ppm hexane five days per week for 11 weeks developed clear and long-lasting neurotoxic signs, as reflected by a marked decrease in hind-limb grip strength and severe impairment of performance of a multisensory conditioned avoidance response (CAR); transient decreases in undifferentiated motor activity and fore-limb grip strength were also seen. Other rats were only slightly affected by repeated, brief (10 min) exposures to high concentrations (24,000 or 48,000 ppm) of hexane 6 or 12 times per day, five days per week for 18 weeks; when the frequency of exposure to 48,000 ppm hexane was increased to 24 times per day (10 min on and 5 min off), five days per week, for 4 additional weeks, more severe signs of neurobehavioral toxicity appeared.

Animals↗