Isooctadecyl isooctadecanoate

Endpoint summary

Additional information

Justification for read-across

There are only limited data available on the genetic toxicity of isooctadecyl isooctadecanoate (CAS 41669-30-1). In order to fulfil the standard information requirements set out in Annex VII and VIII, 8.4, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across 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 to avoid the need to test every substance for every endpoint).

Overview of genetic toxicity

CAS	Chemical name	Molecular weight	In vitro: gene mutation in bacteria	In vitro: cytogenicity	In vitro: gene mutation in mammalian cells	In vivo: cytogenicity
41699-30-1	isooctadecyl isooctadecanoate	536.95	Experimental result: not mutagenic	RA: CAS 93803-87-3	RA: CAS 3687-45-4	RA: CAS 93803-87-3
93803-87-3	2-octyldodecyl isooctadecanoate	565.01	Experimental result: not mutagenic	Experimental result: not clastogenic	--	Experimental result: not clastogenic
3687-45-4	(Z)-octadec-9-enyl oleate	532.92	--	Experimental result: not clastogenic	Experimental result: not mutagenic	--

The above mentioned substances are considered to be similar to each other based on structurally similar properties and/or activities. Therefore, the available data on the source substances has been read-across to isooctadecyl isooctadecanoate (CAS 41669-30-1).

The target substance is characterized by a branched C18 fatty acid esterified with an aliphatic, but branched C16 and C18 alcohol. Both source substances are structurally very similar to the target substance. They are characterized by isostearic acid esterified with a branched alcohol (2-octyldocdecanol) and oleic acid esterified with oleyl alcohol, respectively. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Discussion

 

Genetic toxicity endpoint

 

CAS 41669-30-1

 

The registered substance was investigated for mutagenicity to bacteria (Ames test) according to OECD TG 471 and in compliance with GLP (Harmand, 2002). The Salmonella typhimurium strains TA 1535, TA 1537, TA 100, TA 98 and E. coli WP2 uvrA (pKM101) were exposed to concentrations ranging from 50-5000 µg/plate in the presence or absence of metabolic activation system (S9-mix) in two independent assays. The experiments were conducted according to the plate incorporation methodology, except in the second assay with metabolic activation where the pre-incubation methodology was used. No cytotoxic effects were evident with and without S9-mix up to the highest concentration tested. No increase in the mean number of revertants was observed in any tester strain independent of metabolic activation. Appropriate solvent and positive controls were included into the test and gave the expected results. Based on these results, the test item was considered to be not mutagenic to bacteria under the conditions of the test. 

 

 

CAS 3687-45-4

An in vitro mammalian cell gene mutation assay was performed using oleyl oleate (CAS 3687-45-4), according to OECD TG 476 (Poth, 1994). Chinese hamster lung fibroblasts (V79) were treated with oleyl oleate at concentrations of up to 100 µg/mL for 4 h both with and without metabolic activation. After an expression time of 7 days in growth medium, cells were incubated for 9 or 12 days with 6-thioguanine as selection agent for forward mutation at the HPRT locus. Both with and without metabolic activation, no increases in mutant frequency were observed in the initial and in the confirmatory gene mutation assay. There was no evidence of excessive cytotoxicity (i.e., < 10 % relative cloning efficiency) at any of the tested concentrations either in the presence or absence of metabolic activation in any of the experiments performed. Based on these results, the test item was considered to be not mutagenic to mammalian cells under the conditions of the test.

 

CAS 93803-87-3

An in vitro chromosomal aberration test was performed with 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) according to OECD TG 473 (Bertens, 1998). Cultured human peripheral lymphocytes were exposed to the test substance at concentrations up to 1000 µg/mL, with and without metabolic activation (S9-mix). In experiment 1, a short-term treatment (3 h) with harvest time 24 and 48 h, was performed with metabolic activation; while the 24 h treatment time with 24 h harvest time and 48 h treatment time with 48 h harvest time, respectively, was done without metabolic activation. In experiment 2, both the 3 h treatment with metabolic activation and the 24 h treatment without metabolic activation had a harvest time of 24 h. The test material did not induce a statistically significant increase in the frequency of cells with chromosome aberrations, with or without metabolic activation. The mitotic indices of the treated cultures without metabolic activation were 81-113% and with metabolic activation 68-108%, compared with the vehicle control. No cytotoxicity was noted at any concentrations, but precipitation was observed at concentrations from 1000 µg/mL and above. The vehicle and positive controls were valid. Based on these results, the test item was considered to be not clastogenic to mammalian cells under the conditions of the test.

 

An in vivo mammalian erythrocyte micronucleus test was performed according to OECD TG 474, using 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) (Bertens, 1998). 5 mice/sex/dose were administered 500, 1000 and 2000 mg/kg bw of the test substance via intraperitoneal injection and sacrificed after 24 h. An additional control group and 2000 mg/kg bw treatment group were sacrificed after 48 hours. Bone marrow cells from the femur were extracted, and 2 slides per animal were prepared and stained according to the ‘Wright-stain-procedure’. No increase in the frequency of micronucleated polychromatic erythrocytes was observed in the isolated polychromatic erythrocytes. The treatment groups did not show a decrease in the ratio of polychromatic to normochromatic erythrocytes, compared with the vehicle control groups. No toxicity was observed up to and including the limit dose of 2000 mg/kg bw. The positive control substance (cyclophosphamide) induced a statistically significant increase in the number of micronucleated polychromatic erythrocytes and a reduction in the ratio of polychromatic to normochromatic erythrocytes compared with the vehicle controls, showing the positive control was valid. Based on these results, the test item was considered to be not clastogenic to mammalian cells under the conditions of the test.

Conclusions for Genetic toxicity

Based on read-across and substance-specific data, sufficient evidence is available to conclude that the substance isooctadecyl isooctadecanoate(CAS 41669-30-1) is not mutagenic nor clastogenic.

Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted from substance-specific data and by means of read-across from structural analogues. 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:
In vitro:
Gene mutation in bacteria (Reverse Mutation Test, OECD 471): negative with and without metabolic activation in S. typhimurium TA 98, TA 100, TA 1535, TA 1537 and E.coli WP2 uvr A pKM.
Cytogenicity in mammalian cells (Chromosomal Aberration, OECD 473): negative in human peripheral lymphocytes with and without metabolic activation
Gene mutation in mammalian cells (HPRT, OECD 476): negative in V79 cells with and without metabolic activation
Chromosome aberrration (micronucleus assay, OECD 474): negative (3 concentrations (500, 1000 and 2000 mg/kg bw) intraperitoneally applied to mice)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on substance-specific data and read-across from structurally similar substances, the available data on genetic toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.