The commercial isomer mixture of diethylbenzene (DEB mixture), 1,2-diethylbenzene (1,2-DEB), 1,3-diethylbenzene (1,3-DEB) and 1,4-diethylbenzene (1,4-DEB) were administered orally to male Sprague-Dawley rats. The experimental rats and the appropriate controls were examined electrophysiologically for motor and sensory conduction velocities (MCV and SCV), and for the amplitude of the sensory action potential (ASAP) of the tail nerve, at weekly or bi-weekly intervals. Oral administration of DEB mixture (750 or 500 mg kg-1, once daily, 5 days per week for 10 weeks) and 1,2-DEB (100 mg kg-1, once daily, 4 days per week for 8 weeks) produced a time-dependent decrease in MCV, SCV and ASAP. Rats treated with DEB mixture and 1,2-DEB exhibited a blue discoloration of tissues and urine. No changes in MCV, SCV and ASAP developed in rats administered orally with 1,3-DEP and 1,4-DEB (500 mg kg-1, once daily, 5 days per week for 8 weeks). The results indicate that 1,2-DEB is the isomer responsible for neurotoxicity and suggest that a metabolic pathway giving rise to coloured compounds is involved in the neurotoxicity of DEB.

The role of 1,2-diacetylbenzene (1,2-DAB) in the peripheral nerve toxicity of 1,2-diethylbenzene (1,2-DEB) was investigated in rats. Gas chromatography-mass spectrometry identified 1,2-DAB in the urine samples of rats given 165 mg kg-1 1,2-DEB orally on four consecutive days. 1,2-DAB shared not only the ability of 1,2-DEB to cause bluish discoloration of skin, internal organs and urine, but unlike 1,2-DEB it turned hair blue at the site of intraperitoneal injection. Intraperitoneal administration of 10 mg kg-1 and 20 mg kg-1 1,2-DAB to groups of 12 rats, 4 days a week for 11 and 6 weeks, caused a dose- and time-dependent decrease in mean sensory and motor conduction velocities. Recovery in a 5-week post-exposure period was gradual but consistent. The effect of 1,2-DAB on the amplitude of the sensory action potential was ambiguous. The findings support the hypothesis that the formation of 1,2-diacetylbenzene derivatives contributes to the neurotoxicity of 1,2-DEB.

Brainstem auditory and visual evoked-potentials were studied in male Sprague-Dawley rats during subchronic oral treatment with three unsaturated aliphatic nitriles. The rats were given, by gastric intubation, doses of 10, 20 and 40 mg ¡ kg ª1 3-butenenitrile (allyl cyanide) and 25, 50 and 100 mg ¡ kg ª1 of either cis/trans-2-butenenitrile (crotononitrile) or cis-2-pentenenitrile once a day, 5 days per week for 12 weeks. Oral administration of the three unsaturated nitriles produced deafness and absence of reaction when the animals were subject to droptest. Rats in the high dosage groups exhibited a complete disappearance of the five waves of the auditory evoked-potentials. There was a decrease in the amplitudes of the 2nd component of the auditory evoked-potentials. Those changes were not reversible at the 8th week of the recovery period. A dose-dependent effect on inner and outer hair cells was observed in the organ of Corti. The basal part of the cochlea was the most affected. Though no measurements were made of systemic exposure, a tentative ranking of decreasing ototoxicity of these three unsaturated nitriles might be proposed based on the electrophysiological deficiencies and histological losses observed: 3-butenenitrile Ͼcis-2-pentenenitrile Ͼcis/trans-2-butenenitrile. Moreover, rats treated with those nitriles showed a corneal opacity as well as a decrease in the amplitude and lengthening of the peak latencies of the visual evoked-potentials. These latter changes were reversible by the end of the 8th week of the recovery period and appeared to be related to the opacity of the cornea.

The expiratory bradypnoea indicative of upper airway irritation in mice was evaluated during a period of 60 min of oronasal exposure to acetic acid, hydrogen peroxide and peroxyacetic acid vapours. The airborne concentration resulting in a 50% decrease in the respiratory rate of mice (RD50) was calculated for each chemical. The concentration-response curves of acetic acid, hydrogen peroxide and peroxyacetic acid had similar slopes. The results did however show that the three chemicals had different irritant potencies. The RD50 values of acetic acid, hydrogen peroxide and peroxyacetic acid were 227, 113 and 5.4 p.p.m. respectively. Moreover, a mixture containing 53% acetic acid, 11% hydrogen peroxide and 36% peroxyacetic acid had an RD50 of 10.6 ppm, 3.8 ppm being peroxyacetic acid, which is 1.4 times lower than the theoretical value estimated from the fractional concentrations and the respective RD50s of the individual components. On the basis of a TLV-STEL (threshold limit value for short-term exposure limit) equal to 0.1 RD50, the TLV-STELs for acetic acid, hydrogen peroxide and peroxyacetic acid should not exceed 20, 10 and 0.5 p.p.m. respectively. On the basis of a TLV-TWA (time-weighted average) equal to 0.03 RD50, the TLV-TWAs for these same chemicals should not exceed 5, 3 and 0.2 p.p.m. respectively. Finally, these values and existing TLVs in Europe and the USA are compared.

No abstract