The sub-chronic toxicity in rats of isoparaffinic solvents

• Published in: Regulatory toxicology and pharmacology 2013-12, Vol.67 (3), p.446-455
• Main Authors: Carrillo, Juan-Carlos, David Adenuga, M., McKee, Richard H., Roth, Randy N., Steup, David, Simpson, Barry J.
• Format: Article
• Language: English
• Subjects: Animals; Dose-Response Relationship, Drug; Female; Hydrocarbon solvent; Inhalation Exposure; Inhalation toxicity; Isoalkane; Isoparaffin; Kidney - drug effects; Liver - drug effects; Liver enlargement; Male; No-Observed-Adverse-Effect Level; Occupational exposure limit; Organ Size - drug effects; Organ Specificity; Paraffin - chemistry; Paraffin - toxicity; Rats; Rats, Wistar; Solvents - chemistry; Solvents - toxicity; Structure-Activity Relationship; Sub-chronic toxicity; Toxicity Tests, Subchronic; UVCB; Volatilization; α2u-Globulin
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2013.09.004

•Repeated exposures to an isoparaffinic hydrocarbon solvent produced effects in rats.•The effects were either adaptive or species-specific (α2u-globulin) and not relevant to humans.•Similar effects were observed in other studies of isoparaffinic solvents.•The results can be used to characterize the hazards of C9–C14 aliphatic solvents. Results from a 13-week inhalation study in rats on a C10–C12 isoparaffinic solvent are compared to the results of repeated inhalation and oral toxicity studies of four other isoparaffinic hydrocarbon solvents. Statistically significant findings which were consistent across all studies included: nephropathy and small but significant changes in hematological parameters in male rats and liver enlargement in both male and female rats. The male rat kidney changes were due to an alpha 2u globulin process and not relevant for human health or risk assessment. The liver enlargement without pathologic changes or elevations in liver enzyme markers was considered to be an adaptive response. The reason for the reductions in hematological parameters that were observed in males only is not clear, but it is suggested that these were either due to normal variation or a secondary consequence of the nephropathy. The overall No Observed Adverse Effect Concentration (NOAEC) was the highest concentration tested in the study, >10,000mg/m3. Because of the overall pattern of response, this solvent is considered to be representative of low aromatic C9–C14 aliphatic solvents in general. The data are useful for risk assessment and other purposes including the development of occupational exposure recommendations.