Alcohols, C16-18, ethoxylated, phosphates

Endpoint summary

Additional information

Justification for grouping of substances and read-across

There are no sufficient data available for genetic toxicity ofAlcohols, C16-18, ethoxylated, phosphates(CAS 106233-09-4). In order to fulfil the standard information requirements set out in Annex VIII in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was 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, 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,Alcohols C16-18 (even numbered), ethoxylated (< 2.5 EO)(CAS68439-49-6) is selected as source substances for assessment of genetic toxicity (cytogenicity and gene mutation in mammalian cells).

Genetic toxicity

	Target substance(a)	Source substance(b)
CAS	106233-09-4	68439-49-6
Chemical name	Alcohols, C16-18, ethoxylated, phosphates	Alcohols C16-18 (even numbered), ethoxylated (< 2.5 EO)
MW	322.42 – 867.27 g/mol	242.5 – 402.7 g/mol
Genetic Toxicity in vitro: gene mutation in bacteria	Experimental result:negative	Experimental result:negative
Genetic Toxicity in vitro: cytogenicity in mammalian cells	RA: 68439-49-6	Experimental result:negative
Genetic Toxicity in vitro: gene mutation in mammalian cells	RA: 68439-49-6	Experimental result:negative

(a) The substance subject to the REACh Phase-in registration deadline of 31 May 2013 is indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

(b) Reference (read-across) substances are indicated in normal font.

The read-across is mainly based on similar precursers/breakdown products of the target and the source substances. The available endpoint information is used to predict the same endpoint forAlcohols, C16-18, ethoxylated, phosphates(CAS 106233-09-4).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

There is an Ames test available withAlcohols, C16-18, ethoxylated, phosphates (CAS 106233-09-4). Furthermore a chromosome aberration assay and HPRT assay are available withAlcohols C16-18 (even numbered), ethoxylated (< 2.5 EO) (CAS 68439-49-6).

The mutagenicity ofAlcohols, C16-18, ethoxylated, phosphatesin bacteria was assessed in a study performed according to OECD Guideline 471 with Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and Eschericia coli WP2 uvr A (Thompson, 2012). The tester strains were treated using the plate incorporation and the pre incubation method both with and without S9-mix. The concentrations for both testing methods was 50, 150, 500, 1500, and 5000 µg/plate. In the standard plate test an additional concentration of 2500 µg/plate was used. Results achieved with vehicle (tetrahydrofuran) and positive controls were valid. No cytotoxicity and no genotoxicity were seen in the presence and absence of metabolic activation forAlcohols, C16-18, ethoxylated, phosphates. Precipitation was observed at and above 1500 µg/plate.

The clastogenic potential was assessed in a chromosomal aberration test withAlcohols C16-18 (even numbered), ethoxylated (< 2.5 EO)(CAS 68439-49-6) in mammalian cells according to OECD Guideline 473. Chinese hamster ovary cells (CHO) were exposed to 313, 625, 1250, 2500 and 5000 µg/mL in the presence and 1.25, 2.5, 5, 10, 20, 39 and 78 µg/mL in the absence of metabolic activation. Positive and vehicle (1% ethanol) control cultures were included in each assay. No increases in the number of chromosome aberrations in the presence or absence of metabolic activation were seen at any concentration tested. Appropriate reference mutagens used as positive controls showed a significant increase in chromosome aberrations, thus indicating the sensitivity of the assay, and the efficacy of the S9-mix. Hence, the test substance is not regarded as clastogenic.

The mutagenic potential in mammalian cells was assessed withAlcohols C16-18 (even numbered), ethoxylated (< 2.5 EO)(CAS 68439-49-6) by a HPRT-assay according to OECD Guideline 476. Following pre-tests with the concentration ranging from 1-100 µg/mL, the latter being the solubility limit of the test substance, Chinese hamster ovary cells (CHO) were exposed for 4 h to concentrations of 1.8, 6, 18, 60 and 100 µg/mL in the absence and presence of metabolic activation by rat liver S9-mix. No dose-related increases in mutant colony numbers were obtained in two independent experiments with the test substance in either the presence or absence of S9-mix. Appropriate reference mutagens used as positive controls produced highly significant increases in mutation frequency, thus indicating the sensitivity of the assay. Therefore, the test substance is regarded as not mutagenic in mammalian cells.

In general, alcohol ethoxy sulphates and phosphates did not show any mutagenic potential. This is supported by the conclusions of the HERA report for alcohol ethoxy sulphates (AES) summarising “In all available in vitro and in vivo genotoxicity assays, there is no indication of genetic toxicity of AES.” (HERA report, 2003; EPA, 2009).

Furthermore, sulphates and phosphates of ethoxylated alcohols are expected to have no genotoxic properties based on their chemical structure (EPA, 2009). This result was based on a QSAR prediction performed with DEREK for Windows (V11) with Alcohol C8, ethoxylates (POE = 4), phosphates and Alcohol C8, ethoxylates (POE = 4), sulphates as representative substances (EPA, 2009).

Conclusion

Based on the available data fromAlcohols, C16-18, ethoxylated, phosphates (parent substance and breakdown product) and QSAR information on sulphates and phosphates of ethoxylated alcohols, Alcohols, C16-18, ethoxylated, phosphates is not expected to possess a genotoxic potential.

Justification for selection of genetic toxicity endpoint
No endpoint selected as all three in vitro studies were negative.

Short description of key information:
In vitro:
Bacterial mutagenicity (equivalent to OECD TG 471, GLP, RL2): negative
In vitro mammalian cytogenicity (according to OECD TG 473, GLP, RL2): negative
Mammalian mutagenicity (according to OECD TG 476, GLP, RL2): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available in vitro data are reliable and suitable for classification. Based on the data, classification for genetic toxicity according to Regulation (EC) 1272/2008 or Directive 67/548/EEC is not warranted.