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Administrative data

Description of key information

No key oral repeated dose toxicity studies were identified for n-pentane, 2-methylbutane, or cyclopentane. Supporting repeated dose toxicity studies via the oral route were identified for n-pentane and 2-methylbutane. However, several study limitations are noted when comparing each of the study’s methods to OECD 407. First, female rats were not used in the study. Second, the selected dose levels did not cover an appropriate range (only two dose groups were used, and both were at fairly high doses for a substance that can be aspirated). Third, the substance was administered 5 days/week instead of 7. Fourth, body weight measurements were only taken twice during the experiment (prior to dosing and at the scheduled sacrifice). Fifth, the only post-necropsy examinations were of the kidney. Finally, functional observations, haematology analysis, urinalysis and other post-necropsy examinations were not conducted. Consequently, these studies were not considered key. The results from these acute oral studies (Halder et al. 1985) as well as an oral developmental toxicity study (Trimmer et al. 1997) in rats with pentanes confirm that these substances are not toxic by oral administration either under acute or repeated dose conditions. No dermal repeated dose toxicity studies, key or read across, were identified for n-pentane, 2-methylbutane, or cyclopentane. The physicochemical and toxicological properties of pentanes do not suggest potential for a significant rate of absorption through the skin. The physicochemical properties of these substances (i.e. log Kow is 3.45 (Lide et al. 2008); water solubility 38.5 mg/L at 20°C (McAuliffe, 1966)) indicate that they will not readily penetrate the skin, and hence dermal toxicity is not a significant cause for concern. With regard to the inhalation route, the following repeated dose toxicity studies were identified: a supporting subacute inhalation study from n-pentane; a key 90-day inhalation study (OECD 413) on n-pentane; a read-across 90 -day inhalation study (OECD 413) on 2 -methylbutane (i. e., 33% 2 -methylbutane); and a read-across 90 -day study (non-guideline) on cyclopentane. Information on these studies is presented below. 

Key value for chemical safety assessment

Additional information

No key oral or dermal repeated dose toxicity studies were identified. The results from acute oral studies as well as an oral developmental toxicity study in rats with pentanes confirm that these substances are not toxic by oral administration either under acute or repeated dose conditions. The physicochemical and toxicological properties of pentanes do not suggest potential for a significant rate of absorption through the skin, and hence dermal toxicity is not a significant cause for concern.

With regard to the inhalation route, the following repeated dose toxicity studies were identified: a supporting subacute inhalation study (OECD 412) from n-pentane, in which the NOAEC was determined to be 1000 ppm based on an increase in calcium and phosphorus levels in male rats; a key 90-day inhalation study (OECD 413) on n-pentane that showed that at concentrations ≤ 20,000 mg/m3 n-pentane did not cause any observable adverse effects in male or female rats; a read-across 90-day inhalation study (OECD 413) on 2-methylbutane, in which the NOEC of the test substance was found to be > 2220 ppm for subchronic toxicity, and ≥ 6646 ppm for neurotoxicity; and a read-across 90-day study (non-guideline) on cyclopentane that showed no abnormalities in rats during clinical, neurofunctional, and clinico-pathological examinations in any of the test groups, as well as no changes found during necropsy or in the histo- and neuropathological examinations.

Justification for classification or non-classification

Using key and read-across information from repeated dose inhalation toxicity studies performed with pentanes, it can be assumed that n-pentane would not produce significant systemic toxicity when administered via inhalation. Although there were no key repeated dose toxicity studies identified for dermal exposure, physiochemical data suggests that absorption via the dermal route is not significant and that dermal toxicity is not a significant cause for concern. Additionally, acute oral toxicity data suggests that absorption via the oral route is not significant and that oral toxicity is not a significant cause for concern. Therefore, n-pentane is not classified under EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008 for repeated dose toxicity.