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Administrative data

Key value for chemical safety assessment

Additional information

Justification for grouping of substances and read-across

There is one study available for mutagenic toxicity of 1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-43) in bacterial cells which covers the standard information requirements set out in Annex VII, 8.4.1. In order to fulfil the standard information requirements set out in Annex VIII, 8.4.2 and 8.4.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across to 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, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substances 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7) and Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) are selected as source substances for hazard assessment. 

Bacterial reverse mutation assay (Ames test)

CAS 85711-80-4

1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-43) was tested for mutagenicity in S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 according to OECD Guideline 471 and GLP (Thompson, 1999). Test substance concentrations of 50, 150, 500, 1500 and 5000 µg/plate were tested in acetone in triplicates in two independent experiments. The plate incorporation method with and without the addition of a rat liver homogenate metabolising system (S9-mix) was used in both experiments.

No cytotoxicity was observed. No increase in the frequency of revertant colonies compared to concurrent negative controls were observed in all tested strains, neither in the presence nor in the absence of metabolic activation. Thus, the test substance did not induce gene mutations in the five tested Salmonella strains under the given test conditions.

In summary, due to the negative results, 1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates is expected not to be mutagenic in bacteria.

In vitro cytogenicity in mammalian cells

Since no studies are available to evaluate the clastogenic properties of 1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-43), in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, read-across to the structurally related analogue substances 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7), and Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) was conducted.

CAS 131459-39-7 

An in vitro mammalian chromosome aberration test was performed with 3,5,5-trimethylhexanoic acid mixed tetraesters with pentaerythritol and valeric acid (CAS 131459-39-7) in primary human lymphocytes according to OECD Guideline 473 (Wright, 1999). Duplicate cultures were evaluated for chromosome aberrations in the presence and absence of metabolic activation (rat liver S9-mix).

In the first experiment test substance concentrations of 39.06, 78.13, 156.25, 312.5; 625; 1250; 2500 and 5000 µg/mL in acetone were used for 4 hours of exposure with and without metabolic activation. In the second experiment 39.06, 78.13, 156.25, 312.5, 625, 1250, 2500, and 5000 µg/mL were used for 24 hours exposure without S9 and 39.06, 78.13, 156.25, 312.5, 625, 1250, 2500 and 5000 µg/mL for 4 hours with S9. Ethylmethanesulphate and cyclophosphamide were used as positive control substances. Evaluation of 200 cells from each culture for chromosomal aberrations revealed no increase in the frequency of chromosome aberrations at any dose level in comparison to the negative controls. The test material showed no cytotoxicity. All vehicle (solvent) controls had frequencies of cells with aberrations within the range expected for normal human lymphocytes. All the positive controls induced statistically significant increases in the frequency of cells with aberrations indicating the satisfactory performance of the test and of the activity of the metabolising system. The test material did not induce a statistically significant increase in the frequency of cells with chromosome aberrations in either the absence or presence of a liver enzyme metabolising system in either of two separate experiments. The test material was therefore considered to be non-clastogenic to human lymphocytes in vitro.

CAS 68855-18-5

A chromosome aberration test was conducted with Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) according to OECD TG 473 and under GLP conditions in human lymphocytes. Duplicate cultures of human lymphocytes, treated with the test item, were evaluated for chromosome aberrations at three dose levels, together with vehicle and positive controls. Four treatments conditions were used for the study. In Experiment 1, 4 h in the presence of an induced rat liver homogenate metabolising system (S9), at a 2% final concentration with cell harvest after a 20-hour expression period and a 4 h exposure in the absence of metabolic activation (S9) with a 20-hour expression period. In Experiment 2, the 4 h exposure with addition of S9 was repeated (using a 1% final S9 concentration), whilst in the absence of metabolic activation the exposure time was increased to 24 hours. The dose levels used in the main experiments, selected using data from the preliminary toxicity test, were 12.5, 25, 50, 100, 200, 400 µg/mL for all the four treatment conditions. All vehicle (solvent) controls had frequencies of cells with aberrations within the range expected for normal human lymphocytes. All the positive control items induced statistically significant increases in the frequency of cells with aberrations indicating the satisfactory performance of the test and the activity of the metabolising system. The test item did not induce any statistically significant increases in the frequency of cells with aberrations, in either the absence or presence of S9, in two separate experiments. In conclusion, the test item was considered to be non-clastogenic to human lymphocytes in vitro.

In vitro gene mutation in mammalian cells

Since no studies are available to evaluate the mutagenic properties of 1,3-Propanediol, 2,2-dimethyl-, C5-9 carboxylates (CAS 85711-80-43) in mammalian cells, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5, read-across to the structurally related analogue Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) was conducted.

CAS 68855-18-5

A L5178Y mouse lymphoma assay was conducted with Heptanoic acid, ester with 2,2-dimethyl-1,3-propanediol (CAS 68855-18-5) according to OECDTG 476 and under GLP conditions. Two independent experiments were performed. In Experiment 1, L51787Y TK +/- 3.7.3 c mouse lymphoma cells (heterozygous at the thymidine kinase locus) were treated with the test item at eight dose levels, in duplicate, together with vehicle (solvent) and positive controls using 4 h exposure groups both in absence and presence of metabolic activation(2% S9). In Experiment 2, the cells were treated with the test item at eight dose levels using a 4- h exposure group in the presence of metabolic activation (1% S9) and a 24 h exposure group in the absence of metabolic activation. The dose range of the test substance was selected following the results of a preliminary toxicity test and was determined to be 1.6 to 102.5 µg/mL in both the absence and presence of metabolic activation in Experiment 1. In Experiment 2 the dose range was 1.6 to 102.5 µg/mL in the absence of metabolic activation, and 3.2 to 205 µg/mL in the presence of metabolic activation. The maximum dose levels used in the test were limited by precipitate and test substance induced toxicity. A precipitate of the substance was observed at and above 102.5 µg/mL in the mutagenicity test. The vehicle (solvent) controls had acceptable mutant frequency values that were within the normal range for L5178Y cell line at the TK +/- locus. The positive control items induced marked increases in the mutant frequency indicating the satisfactory performance of the test and of the activity of the metabolising system. The test item did not induce any toxicologically significant dose-related increases in the mutant frequency at any dose level, either with or without metabolic activation, in either the first or the second experiment.

Conclusion for genetic toxicity in vitro

Based on the available data on genetic toxicity, neither the source nor the target substance are considered to exhibit genotoxic properties as all conducted in vitro studies did not provide evidence indicative for either mutagenic and/or clastogenic potential of the tested substances.


Justification for selection of genetic toxicity endpoint
Hazard assessment is conducted by means of read-across based on an analogue approach. 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:
Negative results in Salmonella typhimurium TA 98, TA 100, TA 1535, TA 1537, and TA 102 strains with and without metabolic activation (WoE, OECD 471, GLP, substance specific data and analogue approach)
Negative results in mammalian chromosomal aberration test with lymphocytes (WoE, OECD 473, GLP, analogue approach)
Negative results in mammalian cell gene mutation tests using mouse lymphoma cells, with and without metabolic activation (WoE, OECD 476, GLP, analogue approach).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on information received on test substance 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, and are therefore conclusive but not sufficient for classification.