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

Carcinogenicity

Description of key information

Based on read-across using the analogue approach, it is highly unlikely that hydrocarbons C5-C6, n-alkanes, isoalkanes, < 5% n-hexane have a carcinogenic potential. 
Inhalation (similar to OECD 451), rat: NOAEC for oncogenic effects ≥ 31743 mg/m³ (read-across from commercial hexane)
Inhalation (similar to OECD 451), mouse: NOAEC for oncogenic effects in male mice ≥ 31680 mg/m³; NOAEC for oncogenic effects in female mice = 10560 mg/m³ (read-across from commercial hexane)

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on all available data, no carcinogenic potential is expected. The available data do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and therefore are conclusive but not sufficient for classification.

Additional information

There are no data available on carcinogenicity 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).

In a chronic toxicity study similar to OECD 451, the oncogenic effects of inhalation exposure to commercial hexane (51.5% n-hexane) were evaluated in rats and mice (Daughtrey et al., 1999). In part I of the study groups of 50 male and 50 female rats were exposed to 900, 3000 and 9016 ppm of test substance for 6 h/day, 5 days/week, for 2 years. During the study, the animals were examined for clinical signs, mortality, body weight, opthomological, and food consumption effects. At study termination, animals were sacrificed and gross pathology and histopathology performed. Mortalities of exposure groups were consistent with control groups. Body weight gain was significantly reduced in exposure groups. Histopathology revealed dose-related irritation effects in the nasoturbinal tissue in all exposure groups. Therefore, there was no NOAEC for local irritation effects. No oncogenic effects were seen in the exposure groups. The NOAEC for oncogenic effects is 9016 ppm (corresponding to 31743 mg/m³) in male and female rats.

In part II of the study groups of 50 male and 50 female mice were exposed to 900, 3000 and 9018 ppm (corresponding to 3168, 10560 and 31680 mg/m³) of commercial hexane (51.5% n-hexane) for 6 h/day, 5 days/week, for 2 years. During the study, the animals were examined for clinical signs, mortality, body weight, opthomological, and food consumption effects. Mortalities of exposure groups were consistent with control groups. Histopathology revealed increased liver masses and nodules in female mice in the high exposure group. As referenced by the National Toxicology Program (NTP, 2004), liver tumors in B6C3F1 mice are known to be sensitive to body weight changes, especially in female B6C3F1 mice. Therefore, the increased incidence of liver masses and nodules in female mice are deemed of questionable relevance for human health risk assessment. The NOAEC for oncogenic effects is 31680 mg/m³ in male mice and 10560 mg/m³ in female mice.

It can be assumed that hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane have no carcinogenic potential based on the fact that the source substances were not shown to be mutagenic or clastogenic in the available genetic toxicity studies. Furthermore, the source substances did not produce any evidence of neoplasia in the available repeated dose toxicity studies. Moreover, all source substances are poorly absorbed if ingested. They undergo metabolism, rapid excretion and low deposition; bioaccumulation of the test substance in the tissues is not likely to occur. Therefore, it is concluded that hydrocarbons, C5-C6, n-alkanes, isoalkanes, < 5% n-hexane do not have a carcinogenic potential.

 

Reference not cited in the IUCLID

NTP, 2004: NTP Technical Report on the Toxicology and Carcinogenesis Studies of Stoddard Solvent IIC (CAS No. 64742-88-7) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).NIH Publication No. 04-4453

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