Alcohols, lanolin, distn. residues

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation in bacteria (Ames test): negative in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvrA with and without metabolic activation (OECD 471, GLP)

Cytogenicity: negative in cultured peripheral human lymphocytes with and without metabolic activation (OECD 473, GLP)

Gene mutation in mammalian cells: negative in Mouse lymphoma L5178Y cells without metabolic activation (OECD 476, GLP)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Justification for grouping of substances and read-across

There are no genetic toxicity studies available for Alcohols, lanolin, distn. residues (CAS No. 90622-40-5). In order to fulfil the standard information requirements set out in Annex VII-VIII, 8.4, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from an analogue substance is conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, the substance Alcohols, lanolin (CAS No. 8027-33-6) is selected as reference substance for assessment of genetic toxicity.

The read-across is mainly based on the common origin of the source and target substances, as the target substance is generated from the source substance by distillation, the target substance being the high-boiling fraction (residue) of the distillation process. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Gene mutation in bacteria

A bacterial reverse mutation assay was conducted with Alcohols, lanolin according to OECD guideline 471 under GLP conditions (Bowles and Thompson, 2010). The tester strains Salmonella typhimurium TA1535, TA1537, TA98 and TA100 and Escherichia coli WP2 uvrA were treated with the test item in two independent experiments (plate incorporation and pre-incubation method, respectively) at five concentrations from 50 to 5000 µg/plate, in triplicate, both in the presence and absence of metabolic activation (S9-mix). Appropriate vehicle (acetone) and positive control substances were included.

No cytotoxicity was observed up to the highest concentration tested. A greasy, particulate precipitate was observed at and above 1500 µg/plate, without preventing the scoring of revertant colonies. No significant increases in the frequency of revertant colonies were noted for any of the bacterial strains either with or without metabolic activation. The vehicle and positive control plates showed the expected results.

Under the conditions of the study, the test material was considered to be not mutagenic.

In vitro cytogenicity

The substance Alcohols, lanolin was tested for the induction of chromosome aberrations in a GLP-compliant study performed according to OECD guideline 473 (Bowles, 2010). Based on the results of a preliminary toxicity study, duplicate cultures of human lymphocytes were treated with the test item at six concentrations ranging from 39.06 to 625 or 1250 µg/mL with and without metabolic activation (S9-mix); up to four concentrations were selected for assessment of chromosome aberrations. Appropriate solvent (acetone) and positive control substance were included in the assay. Three treatment conditions were used: 4 h exposure without metabolic activation followed by a 20 h expression period; 4 h exposure with metabolic activation followed by a 20 h expression period; and 24 h continuous exposure without metabolic activation.

The test item was not toxic after 4 h exposure with and without metabolic activation, but it was toxic after 24 h continuous exposure without metabolic activation at 625 µg/mL. The test item did not induce any toxicologically statistically significant increases in the frequency of cells with aberrations, under any of the treatment conditions, using a concentration range that included a concentration level that induced 50% mitotic inhibition or was the lowest precipitating concentration, depending on the treatment conditions. The solvent and positive control treated cells showed the expected results.

Under the conditions of the study, the test item was considered to be not clastogenic to human lymphocytes in vitro.

In vitro gene mutation in mammalian cells

A mouse lymphoma assay was conducted with Alcohols, lanolin according to OECD guideline 476 and in compliance with GLP (Brown, 2010). L5178Y TK+/- 3.7.2c mouse lymphoma cells were treated with the test item at six concentration levels, in duplicate, along with appropriate vehicle (acetone) and positive controls. Cells were exposed for 4 h with and without metabolic activation (S9-mix) and 24 h without metabolic activation.

The concentration range of test item was selected based on the results of a preliminary toxicity test and was 39.06 to 937.5 µg/mL for the 4 h exposure assays and 39.06 to 312.5 µg/mL for the 24 h exposure assay.

The maximum dose level used in the mutagenicity test was limited by the estimated maximum exposure to the test item and test item-induced toxicity. The test item did not induce any toxicologically significant or dose-related increases in the mutant frequency at any dose level, either with or without metabolic activation, in any of the three exposure groups. The solvent and positive control treated cells showed the expected results.

Under the conditions of the study, the test substance was considered to be not mutagenic to L5178Y cells.

Conclusions for (in vitro) genetic toxicity

There are no in vitro genetic toxicity studies available for Alcohols, lanolin, distn. residues. In order to fulfil the standard information requirements of Annex VII-VIII, Section 8.4, of Regulation (EC) No 1907/2006, hazard assessment is conducted by means of read-across from the source substance Alcohols, lanolin in accordance with Annex XI, Section 1.5.

The substance Alcohols, lanolin has been tested for the induction of gene mutations in bacteria and mammalian cells as well as for the induction of chromosome aberrations in human cells. The results of all available studies were negative. Thus, the substance is considered to be not mutagenic or clastogenic in vitro.

Based on the read-across approach, the substance Alcohols, lanolin, distn. residues is considered to be not mutagenic or clastogenic in vitro.

Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of read-across from a structural analogue/surrogate. No study was selected, since all available in vitro genetic toxicity studies were negative. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Short description of key information:
Based on read-across from Alcohols, lanolin (CAS No. 8027-33-6):
Gene mutation in bacteria (Ames test): negative in S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvrA with and without metabolic activation (OECD 471, GLP)
Cytogenicity: negative in cultured peripheral human lymphocytes with and without metabolic activation (OECD 473, GLP)
Gene mutation in mammalian cells: negative in Mouse lymphoma L5178Y cells without metabolic activation (OECD 476, GLP)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on read-across from the source substance Alcohols, lanolin (CAS No. 8027-33-6) following an analogue approach, the available data on the genetic toxicity of Alcohols, lanolin, distn. residues do nor meet the classification criteria according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.