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

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are no data available on skin sensitisation 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).

For n-pentane, a study was conducted using guinea pigs (20 females/dose; 15 females for positive control; Trimmer, 1991). For the induction phase, six intradermal injections (0.1 mL each) were administered to three different sites as follows: Site 1: FCA/water to treated and control groups; Site 2: 5.0% n-pentane in carrier (ethanol) to the treated group, 100% ethanol to the control group; Site 3: 5.0% n-pentane in FCA/Water to the treated group, 5.0% carrier (reverse osmosis water) in FCA/Water to the control group. On day 7 following injection, 0.5 mL of a mild to moderately irritating dose of n-pentane was administered topically over the previously injected areas and covered with occlusive wrapping. Control animals received topical carrier applications instead. The challenge phase was conducted 21 days post induction phase. n-Pentane (0.1 mL of n-pentane; 1.0% in ethanol) was applied topically to the left flank of both treated and control irritation groups. All animals survived to study termination and displayed a weight gain from their day 0 values. Abnormal clinical observations during scheduled intervals were limited to one treated group animal that was emaciated and had a small amount of stool. Another animal exhibited slight emaciation and poor food consumption. Clinical signs observed in these two animals were considered to be correlated to the stress of the wrapping procedure and not treatment-related. No signs of dermal irritation were observed at any dose in either patch group. DNCB elicited positive reactions from all tested animals 24 and 48 hours after removal of the patch challenge. Based on the lack of signs dermal irritation observed in the study, n-pentane was not considered a dermal sensitiser.

In the sensitisation study of hexane (Basketter et al., 2000), a local lymph node assay (LLNA) was done to determine the concentration of hexane that would be expected to cause sensitisation in humans. Results of previous LLNA experiments were used to calculate the EC3 value, the concentration at which the test substance would produce a 3 -fold increase in the proliferative activity of lymph nodes in the LLNA test. The 3 -fold increase is considered a positive response for sensitization in the LLNA test. The EC3 value for hexane was determined to be > 100% concentration. The substance is therefore not sensitising.

Taking into account all available data, there was no indication of skin sensitisation for the source substances n-pentane and hexane. Based on the read-across approach, hydrocarbons, C5 -C6, n-alkanes, isoalkanes, < 5% n-hexane are not considered to be skin sensitising.

Migrated from Short description of key information:
Based on read-across using the analogue approach, hydrocarbons C5-C6, n-alkanes, isoalkanes, < 5% n-hexane are not considered to be a skin sensitiser.
Skin sensitisation test with n-pentane (similar to OECD 406): not skin sensitising
Local lymph node assay with hexane (similar to OECD 429): not skin sensitising

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on read-across within an analogue approach, the available data on skin sensitisation 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.