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

Endpoint summary

Description of key information

Taking into accout all available data on source substances, hydrocarbons C5-C6, n-alkanes, isoalkanes, < 5% n-hexane are considered to be irritating to the skin and not irritating to the eyes.
Skin: irritating (based on classification of the source substances)
Eye: not irritating  (read-across from n-pentane and C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane)

Key value for chemical safety assessment

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are no data available on skin and eye irritation 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).

Skin irritation

4 male and 2 female New Zealand White rabbits were dermally exposed to 0.5 mL of n-pentane for 4 h to dorsal surface from the shoulder region to the lumbar region of each rabbit (Trimmer, 1990).  Animals were then observed for 7 days. Irritation was scored by the Draize method of scoring. The mean erythema and oedema scores over 24, 48 and 72 h were 0.5 and 0.06, respectively.

For a human study with n-pentane, 30 human volunteers were dermally exposed to n-pentane for 24 h, via a semi-occlusive patch (Rue and Plaza, 1991). Thirty minutes after patch removal, the test sites were scored, and were scored again 24 h after patch removal. Test subjects remained under observation for a maximum of 4 h after exposure. If the test material elicited severe reactions, the patches were removed. The average dermal irritation score for this test material was 0.27 on a scale from 0 to 7 for n-pentane. Therefore, the test substance was not likely to be irritating to humans.

The skin irritancy of a hexane solvent containing <5% n-hexane was examined in the study of Shell (1987). Groups of six rabbits had 0.5 mL of the test substance applied to their dorsal skin. The test area was covered semi-occlusively, and exposure lasted 4 h. The test area was then washed. Animals were evaluated for erythema and oedema at 30 min, 24, 48 and72 h, and 7 days after removal of the test substance. The mean erythema and oedema scores over 24, 48, and 72 h were 0.8 and 0.0, respectively.

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 irritating to the skin. 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 irritating to the skin.

 

Eye irritation

n-Pentane was tested for ocular irritation in 3 New Zealand White rabbits at a single 0.1 mL dose (Frank, 1996). Observations were made at 1, 24, 48, and 72 h after application for indications of ocular irritation. Reactions were scored based on the Draize Standard Eye Irritation Grading Scale (Draize, 1959). n-Pentane caused ocular irritation of the conjunctiva in all three test animals. All animals showed signs of redness at 1 h and 24 h after the instillation. In only one animal did redness persist until the 48 h observation period; this same animal was the only one to exhibit chemosis and discharge responses (at the 1 h interval). All 3 animals were cleared of any ocular irritation at the 72 h observation. The mean conjunctivae, chemosis, iris, and cornea scores over 24, 48 and 72 h were 0.4, 0.1, 0.0, and 0.0 respectively.

The eye irritation potential of the hydrocarbon solvent “C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane” was tested in the study of Hine and Zuidema (1970). 0.1 mL of the test substance was placed in the eyes of six male rabbits. The rabbits were examined for signs of irritation at 24, 48, and 72 h after start of exposure. Only 1 animal showed signs of irritation at 24 h. The mean conjunctivae, chemosis, iris, and cornea scores over 24, 48 and 72 h were 0.1, 0.0, 0.0, and 0.0 respectively.

In conclusion, the available studies indicated that the read-across substances had eye irritation scores but well-below the threshold for classification.

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Based on read-across within an analogue approach, the available data on skin irritation meet the criteria for classification as Category 2 (H315) according to Regulation (EC) 1272/2008 and as Xi; R38 according to Directive 67/548/EEC.

Based on read-across within an analogue approach, the available data on eye irritation 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.