Hydrocarbons, C5-C7, n-alkanes, isoalkanes, < 5% n-hexane

Endpoint summary

Description of key information

Based on read-across using the analogue approach, hydrocarbons C5-C6, n-alkanes, isoalkanes, < 5% n-hexane are not expected to possess systemic toxicity after repeated inhalation exposure.
Inhalation (according to OECD 413), 13 weeks, rat: NOAEC ≥ 20000 mg/m³ (read-across from n-pentane)
Inhalation (similar to OECD 413), 13 weeks, rat: NOAEC (male rat) = 10504 mg/m³; NOAEC (female rat) ≥ 31652 mg/m³ (read-across from commercial hexane)
Inhalation (similar to OECD 413), 13 weeks, mouse: NOAEC ≥ 31652 mg/m³ (read-across from commercial hexane)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are no data available on repeated dose toxicity of hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane. However, there are reliable data available considered suitable for read-across using the analogue approach.

The target substance is a hydrocarbon solvent with carbon numbers in the range of C5 to C6. The main constituents of the mixed solvent consist of about 43% of C6 species and about 57% of C5 species. n-Hexane is only present in concentrations < 5% of the total volume. The source substances chosen for read-across have similar toxicological properties as the target substance. There is only one distinguishing characteristic for n-hexane. n-Hexane has unique toxicological properties due to its ability to be metabolized to the neurotoxic metabolite 2,5-hexanedione. Other C6 species will not be metabolized to 2,5-hexanedione. For this reason, n-hexane and hydrocarbon solvents containing n-hexane at levels greater than 5% represent a worst case scenario.

Taking into account all available data, animal and human toxicity data as well as environmental fate and effects data show that source substances have similar (eco-)toxicological and environmental fate properties as the target substance. Therefore, read-across is performed based on an analogue approach (for details please refer to the analogue justification which is attached in section 13 of the technical dossier).Therefore, read-across is performed based on an analogue approach (for details please refer to the analogue justification which is attached in section 13 of the IUCLID).

In a subchronic inhalation toxicity study, n-pentane was administered to 10 rats/sex/concentration by whole body exposure at analytical concentrations of 5097 ± 79, 10203 ± 151 and 20483 ± 734 mg/m³ 6 h/day and 5 days/week for 13 weeks (Whitman, 1997). There were no treatment-related effects observed for clinical signs, body weight, food consumption, hematology, clinical chemistry, ophthalmology, gross pathology, organ weights, or histopathology.Based on this information, the NOAEC is ≥ 20000 mg/m³.

In a sub-chronic toxicity study of commercial hexane (40-55% n-hexane, > 10% methylcyclopentane), groups of 10 male and 10 female rats were exposed to concentrations of 904, 2984, and 8992 ppm of test substance for 6 h/day, 5 days/week, for 13 weeks via the inhalation route (API, 1990). There was no mortality among the exposed groups, and no treatment related effects to body weight gain. At sacrifice, high exposure males had increased liver weights. There was also found hemorrhage and inflammation in male rat livers at the high dose level. The liver effects appeared to be treatment related. The NOAEC for male rats is therefore 2984 ppm (corresponding to 10504 mg/m³). The NOAEC for female rats is 8992 ppm (corresponding to 31652 mg/m³).

In another study of API (1980), the subchronic toxicity of commercial hexane (40-55% n-hexane, > 10% methylcyclopentane) was investigated in mice. Groups of 10 male and 10 female mice were exposed via inhalation to concentrations of 904, 2984, and 8992 ppm of test substance for 6 h/day, 5 days/week, for 13 weeks. Seven animals died during the study period, however, all deaths were accidental and not considered to be treatment-related. There were no other treatment-related effects observed. The NOAEC for male and female mice is ≥ 8992 ppm (corresponding to 31652 mg/m³).

Using the information from repeated dose inhalation toxicity studies performed with n-pentane and commercial hexane, it can be concluded that also the target substance would not produce significant systemic toxicity when administered via inhalation. Although there were no repeated dose toxicity studies identified for either oral or dermal exposure, physico-chemical data suggests that absorption via the dermal route is not significant and that oral and dermal toxicity is not a significant cause for concern.

However, repeated or prolonged contact of hydrocarbon fluids with skin may cause defatting and drying of the skin. The available data on the source substances within an analogue approach do not support classification of hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane as skin defatting. However, based on the classification of its constituents pentane (Index No 601-006-00-1) and hexane, reaction mass of isomers (containing < 5% n-hexane (Index No 601-007-00-7) as laid down in Annex I of Directive 67/548/EEC and Annex VI of Regulation (EC) No 1272/2008 hydrocarbons, C5-C6, n-alkanes, isoalkanes, <5% n-hexane have to be classified as skin defatting.

Justification for classification or non-classification

Based on read-across within an analogue approach, the available data on repeated dose toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

However, repeated or prolonged contact of hydrocarbon fluids with skin may cause defatting and drying of the skin. Therefore, hydrocarbons C5-C6, n-alkanes, isoalkanes, < 5% n-hexane are also classified as EUH066 according to Regulation (EC) 1272/2008 and as R66 according to Directive 67/548/EEC.