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Neurotoxicity

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Description of key information

Acute CNS effects: NOAEC for in rats: 1500 to 2500 mg/m3 (based primarily on volatility)

Subchronic (13 weeks) neurotoxicity: NOAEC for rats: >24.3 g/m3 (6646ppm)

Key value for chemical safety assessment

Additional information

Four isoparaffinic hydrocarbon solvent products differing in predominant carbon number and volatility (C7-8, C8-9, C10-11, and C11-12) were tested for their acute effects on locomotor activity and operant performance after inhalation exposure in mice. For both measures, concentration effect curves were obtained for 30 min exposures using a within-subject design. The more volatile products, C7-8 and C8-9 isoparaffins, were easily vaporized under the test conditions. C10-11 isoparaffins were slowly volatilized and C11-12 isoparaffins could not be completely volatilized within the 30 min exposures, suggesting that acute human exposures may be less likely. C7-8, C8-9, and C10-11 isoparaffins produced reversible increases in locomotor activity of mice at 4000 and 6000 ppm and reversible decreases in rates of schedule controlled operant behavior in the same concentration range.   The locomotor activity and operant behavior NOAEC for C7-8, C8-9, and C10-11 isoparaffins was determined to be 1000 ppm. The locomotor activity and operant behavior NOAEC for C11-12 isoparaffins was determined to be >2000 ppm as C11-12 isoparaffins did not produce acute CNS effects at the maximally attainable vapor concentrations.

 

In a battery of neurobehavioral tests, the NOAECs for acute CNS effects were determined to be >= 2500mg/m3 for cycloparaffins, >=1500mg/m3 for isoparaffins, and >=1500mg/m3 normal paraffins.

 

In a 13 week subchronic inhalation study, the neurotoxicity of light alkylate naphtha distillate (LAND-2; carbon range C5-C8) was examined in male and female rats. Locomotor activity and a functional operational battery were performed during the pretest week, weeks 5, 9, 14, and 18 (recovery group). Other than acute central nervous system effects, there were no treatment related neurotoxic effects in any of the treatment groups.

 

Justification for classification or non-classification

There are no chronic neurotoxicity specific studies for C9-C14 aliphatic, <2% aromatic hydrocarbon fluids. However, in a 13 week subchronic inhalation study, the neurotoxicity of light alkylate naphtha distillate (LAND-2; carbon range C5-C8) was examined in male and female rats and aside from acute CNS effects, no treatment related neurotoxic effects found in any of the treatment groups. The NOAEC was determined to be > 24.3 g/m3 (6646ppm). Additionally, no neurological effects were reported in the NTP 2 year carcinogenicity study on Stoddard solvent. Therefore, C9-C14 aliphatic, <2% aromatic hydrocarbon fluids are not likely to cause neurotoxicity.