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Administrative data

Key value for chemical safety assessment

Additional information

According to the literature searches, genotoxicity studies related to squalene are limited. The study of raw shark liver oil containing squalene to increase the frequency of micronucleu s was determined . Authors reported that the crude liver oils of three species of sharks are genotoxic in human lymphocytes in vitro (Bartfai et al., 2000 ). On the other hand, several researchers explained that squalene has non-genotoxic properties. These studies indicated that squalene has curative effects on DNA damage using sister chromatid exchange and micronucleus test systems (Fan et al.,

1996; O’Sullivan et al., 2002 ). In addition squalene acts as a protective agent and has been shown to decrease chemo- and radiotherapy-induced side-effects (Xu et al., 2005; Reddy and Couvreur, 2009; Narayan et al., 2010 ). Das et al. (2008) reported that squalene selectively protected mouse bone marrow progenitors against cisplatin and carboplatin-induced cytotocity in vivo without protecting tumor growth. These results are in agreement with Narayan et al.’s (2010) report. They assessed the protective effect of squalene against the genotoxicity of the chemotherapeutic agent doxorubicin using micronucleus and comet assay. They showed that squalene did not induce any significant DNA damage by itself.

They also suggested that the complementary use of squalene with doxorubicin will be beneficial to reduce the adverse effect of doxo-

rubicin in cancer chemotherapy.

The genotoxic potential of the vaccine adjuvant Squalene was assessed by the chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and micronucleus (MNs)tests in human lymphocytes and comet assay in both human and rat lymphocytes . Five different concentrations of squalene (1250–20,000 lg/ml for human lymphocytes and 0.07–1.12mg/kg for rat lymphocytes)were studied. Squalene did not affect the CAs and MN frequency, in all treatment s in vitro . A significant increase in SCEs was observed in almost all concentrations at 24 htreatment. Squalene did not affect significantly the comet tail length (CTL) (except 2500 lg/ml) and comet tail intensity (CTI)at all treatments in vitro. In rats, squalene significantly increased and decreased CTL and CTI in some doses. Although there are increasing and reduction in the effect , squalene cannot be regarded as genotoxic in human lymphocytes.

Bartfai, E., Orsière, T., Duffaud, F., Villani, P., Pompili, J., Botta, A., 2000. Studies on the genotoxic effects of crude liver oils from 3 species of

mediterranean sharks by means of in vitro micronucleus test using human lymphocytes. Ann. Biol. Clin. Paris 58, 595–600.

Fan, S., Ho, I., Yeoh, F., Lin, C., Lee, T., 1996. Squalene inhibits sodium arsenite-induced sister chromatid exchanges and micronuclei in Chinese

hamster ovary- K1 cells. Mutat. Res. 368, 165–169

O’Sullivan, L., Woods, J.A., O’Brien, N.M., 2002. Squalene but not n-3 fatty acids protect against hydrogen peroxide-induced sister chromatid

exchanges in Chinese hamster V79 cells. Nutr. Res. 22, 847–857

Xu, R.B., Liu, W.W., Wang, M.Y., 2005. Progress of preparation and application in squalene. Shand. J. Med. 45, 69–70.

Reddy, L.H., Couvreur, P., 2009. Squalene: a natural triterpene for use in disease management and therapy. Adv. Drug Deliv. Rev. 61, 1412–1426.

Narayan, B.H., Tatewaki, N., Giridharan, V.V., Nishida, H., Konishi, T., 2010. Modulation of doxorubicin-induced genotoxicity by squalene in Balb/c

mice. Food Funct. 1, 174–179.

Das, B., Antoon, R., Tsuchida, R., Lotfi,S., Morozova, O., Farhat, W., Malkin, D., Koren, G., Yeger, H., Baruchel, S., 2008. Squalene selectively protects

mouse bone marrow progenitors against cisplatin and carboplatin-induced cytotoxicity in vivo without protecting tumor growth. Neoplasia 10, 1105–1119.

Justification for selection of genetic toxicity endpoint
No selection is made because the assessment of the genotoxicity is performed as a weight of evidence and the evaluation performed on the basis of the results of the three in vitro tests, mutagenesis on bacteria, on mammalian cells and chromosomal aberration

Short description of key information:
Not mutagenic
Not clastogenic

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The substance is not classified genetic mutagen because it doesn't meet the classification criteria of the CLP regulation n. 1272/2008:

- Category 1 (1A; 1B): substances known to induce heritable mutations or to be regarded as if they induce heritable mutations in the germ cells of humans. Substances known to induce heritable mutations in the germ cells of humans;

- Category 2: substances which cause concern for humans owing to the possibility that they may induce heritable mutations in the germ cells of humans.