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Toxicological information

Carcinogenicity

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Description of key information

No carcinogenicity study is available.

Key value for chemical safety assessment

Additional information

No carcinogenicity study is available. In a 90-day toxicity study conducted with alpha-pinene in mice, minimal to moderate hyperplasia was observed in the transitional epithelium of the urinary bladder. However, these effects are not associated with carcinogenesis:

- alpha-pinene and several other related substances have been tested in a number of in vivo and in vitro mutagenicity tests and have been demonstrated to have no mutagenic potential;

- this absence of mutagenicity includes also alpha-pinene urinary metabolites in rats which were not mutagenic in TA 98 and TA 100 (Rockwell, 1979);

- in the 90-day toxicity study with alpha-pinene in rat, the only finding was alpha 2µ-globulin nephropathy, a male rat-specific pathology, well-known to be irrelevant for humans, and kidney cancer which would appear following these lesions would also be considered as non relevant;

- urinary bladder hyperplasia seems to be specific to mice (it was not observed in rats in either sex). It is a quite common finding in mice and is usually not associated with tumors in oncogenicity studies (Ward et al., 1993; Horn et al., 2007).

Therefore, it is not expected that alpha-pinene may induce hyperplasia or pre-neoplastic lesions relevant for humans. As alpha-pinene, (-)-beta- pinene, delta-3-carene and turpentine oil are structurally related substances, none of these substances are expected to be carcinogenic and a carcinogenicity study is not deemed necessary.

References:

Horn TL et al., Oncogenicity evaluation of resveratrol in p53(+/-) (p53 knockout) mice. Food Chem Toxicol. 2007 Jan;45(1):55-63.

Ward JM et al., Cell proliferation not associated with carcinogenesis in rodents and humans. Environ Health Perspect. 1993 Dec;101 Suppl 5:125-35.

Rockwell P and Raw I., A mutagenic screening of various herbs, spices, and food additives. Nutrition and Cancer. 1979 1(4):10-15

Justification for classification or non-classification

No carcinogenicity study is available. In a 90-day toxicity study conducted with alpha-pinene, only alpha 2µ-globulin nephropathy, a male rat-specific pathology, well-known to be irrelevant for humans, was identified. Moreover, in a 90-day toxicity study conducted with alpha-pinene in mice, minimal to moderate hyperplasia observed in the transitional epithelium of the urinary bladder was observed. However, it is a quite common finding in mice and is usually not associated with tumors in oncogenicity studies (Ward et al., 1993; Horn et al., 2007).

Therefore, it is not expected that alpha-pinene may induce hyperplasia or pre-neoplastic lesions relevant for humans. As alpha-pinene, (-)-beta-pinene, delta-3-carene and turpentine oil are structurally related substances, none of these substances are expected to be carcinogenic.

References:

Horn TL et al., Oncogenicity evaluation of resveratrol in p53(+/-) (p53 knockout) mice. Food Chem Toxicol. 2007 Jan;45(1):55-63.

Ward JM et al., Cell proliferation not associated with carcinogenesis in rodents and humans. Environ Health Perspect. 1993 Dec;101 Suppl 5:125-35.