Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Justification for grouping of substances and read-across

The polyol esters category comprises of 49 aliphatic esters of polyfunctional alcohols containing two to six reactive hydroxyl groups and one to six fatty acid chains. The category contains mono constituent, multi-constituent and UVCB substances with fatty acid carbon chain lengths ranging from C5 - C28, which are mainly saturated but also mono unsaturated C16 and C18, polyunsaturated C18, branched C5 and C9,branched C14 – C22 building mono-, di-, tri-, and tetra esterswith an alcohol (i.e.polyol).

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13) and within Chapter 5.1 of the CSR.

Data matrix for genetic toxicity

CAS

Bacterial gene mutation

cytogenicity in mammalian cells in vitro

Mammalian gene mutation

NPG esters

68855-18-5 (a)

RA: CAS 31335-74-7

OECD 473 ongoing

OECD test 476 ongoing

31335-74-7

negative

RA: CAS 68855-18-5

RA: CAS 68855-18-5

RA: CAS 42222-50-4

70693-32-2

RA: CAS 97281-24-8

RA: CAS 85186-86-3

RA: CAS 403507-18-6

RA: CAS 68855-18-5

RA: CAS 42222-50-4

85186-86-3

negative

negative

RA: CAS 68855-18-5

RA: CAS 42222-50-4

85186-95-4

RA: CAS 85186-86-3

RA: CAS 85186-86-3

RA: CAS 68855-18-5

RA: CAS 42222-50-4

91031-27-5

RA: CAS 85186-86-3

RA: CAS 68855-18-5

RA: CAS 85186-86-3

RA: CAS 68855-18-5

RA: CAS 42222-50-4

42222-50-4

RA: CAS 403507-18-6

RA: CAS 85186-86-3

RA: CAS 403507-18-6

RA: CAS 85186-86-3

negative

85005-25-0

RA: CAS 85186-86-3

RA: CAS 85186-86-3

RA: CAS 68855-18-5

RA: CAS 42222-50-4

TMP esters

78-16-0 (a)

negative

RA: CAS 189120-64-7

RA: CAS 11138-60-6

RA: CAS 85186-89-6

97281-24-8(b)

negative

--

--

189120-64-7

--

negative

--

11138-60-6

--

negative

--

91050-89-4

negative

RA: CAS 11138-60-6

RA: CAS 85186-89-6

85186-89-6

negative

--

negative

403507-18-6

negative

negative

--

68002-78-8

RA: CAS 403507-18-6

RA: CAS 85186-89-6

RA: CAS 403507-18-6

RA: CAS 85186-89-6

68541-50-4

RA: CAS 403507-18-6

RA: CAS 85186-89-6

RA: CAS 403507-18-6

RA: CAS 85186-89-6

PE esters

15834-04-5 (b)

---

---

negative

85116-93-4

negative

---

---

85711-45-1 (a)

RA: CAS 85116-93-4
RA: CAS 85186-89-6

RA: CAS 403507-18-6

RA: CAS 85186-89-6

25151-96-6

RA: CAS 85116-93-4

RA: CAS 403507-18-6

RA: CAS 85186-89-6

67762-53-2


negative

 

RA: CAS 189200-42-8

RA: CAS 15834-04-5

71010-76-9

RA: CAS 68441-68-9
RA: CAS 189200-42-8

RA: CAS 189200-42-8

RA: CAS 15834-04-5

68441-68-9

negative

RA: CAS 189200-42-8

RA: CAS 15834-04-5

85586-24-9

negative

RA: CAS 189200-42-8

RA: CAS 15834-04-5

91050-82-7

RA: CAS 85116-93-4

RA: CAS 403507-18-6

RA: CAS 85186-89-6

19321-40-5

RA: CAS 85116-93-4

RA: CAS 403507-18-6

RA: CAS 85186-89-6

68604-44-4

RA: CAS 85116-93-4
RA: CAS 85186-89-6

RA: CAS 403507-18-6

RA: CAS 85186-89-6

62125-22-8

RA: CAS 85116-93-4

RA: CAS 403507-18-6

RA: CAS 85186-89-6

68440-09-5

RA: CAS 85116-93-4
RA: CAS 85186-89-6

RA: CAS 403507-18-6
RA: CAS 189200-42-8

RA: CAS 85186-89-6
RA: CAS 15834-04-5

189200-42-8

negative

negative

---

 

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

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font.

Lack of data for a given endpoint is indicated by “--“.

Discussion

In vitro gene mutation in bacteria

CAS 31335-74-7

The mutagenic potential of 2,2-dimethyl-1,3-propanediyl dioctanoate (CAS# 31335-74-7) was tested in two reverse mutation assays performed comparable to OECD Guideline 471 and under GLP conditions (Callender, 1995 & 1996). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and E. coli WP2P and WP2 uvrA were used. Within the first experiment, tester strains were incubated with test material concentrations of 100, 200, 500, 1000, 2500 and 5000 µg/plate dissolved in DMSO with and without the addition of a metabolic activation system (phenobarbitale and beta-naphthoflavone induced rat liver S9 mix) in a plate incorporation test. The repeat experiment within both studies was done with an additional 1 hour pre-incubation period. Vehicle and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent vehicle controls was observed in all strains treated with the test substance in both experiments, neither in the presence nor in the absence of metabolic activation. No cytotoxicity was observed. Thus, 2,2-dimethyl-1,3-propanediyl dioctanoate did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested under the conditions of these tests.

CAS 85186-86-3

The mutagenic potential of Fatty acids, C8-18 and C18-unsatd., esters with neopentylglycol (CAS# 85186-86-3) was tested in a reverse mutation assay performed comparable to OECD Guideline 471 and under GLP conditions (Bowles, 2012). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and E. coli WP2 uvrA were used. Tester strains were incubated with test material concentrations of 50, 150, 500, 1500, and 5000 µg/plate dissolved in acetone with and without the addition of a metabolic activation system (phenobarbitale and beta-naphthoflavone induced rat liver S9 mix). The first experiment was a plate incorporation assay and the repeat experiment was carried out using an additional 20 min pre-incubation. Vehicle, negative and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent controls was observed in all strains treated with the test substance, neither in the presence nor in the absence of metabolic activation. No cytotoxicity was observed in the plate incorporation assay. However, cytotoxicity was seen at 5000 µg/plate without S9 mix in the TA100, TA1535 and TA1537 strains in the pre-incubation assay. Thus, Fatty acids, C8-18 and C18-unsatd., esters with neopentylglycol did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested under the conditions of this test.

CAS 78-16-0

There are 4 studies available investigating the mutagenic potential of 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate (CAS# 78-16-0) in bacteria.

In the first study, the mutagenic potential of the test substance was investigated in a reverse mutation assay performed comparable to OECD Guideline 471 and under GLP conditions (Wagner, 1997). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100, TA1538 and E. coli WP2 uvrA were used. Tester strains were incubated with the test material dissolved in ethanol at concentrations of 10, 33, 100, 333 and 1000 µg/plate without metabolic activation and at 33, 100, 333, 1000 and 5000 µg/plate with metabolic activation (Arochlor 1254 induced rat liver S9 mix). Vehicle and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent vehicle controls was observed in all strains treated with the test substance, neither in the presence nor in the absence of metabolic activation. No cytotoxicity was observed, but the test substance was tested up to precipitating concentrations. Thus, 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested under the conditions of this test.

There is a second Ames test available for which only a summary of the results was given (Callander, 1991). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and E. coli WP2P and WP2P uvrA were tested. No test concentrations were given, but all strains were tested in a plate incorporation assay with and without metabolic activation. TA98 and TA100 were additionally tested in a preincubation assay. No increases in the frequency of revertant colonies in the strains treated with the test substance were found.

There are two additional studies available. Another Ames test was conducted which only contained 1 plate per incubation and no repeat experiment. Additionally, gene mutation in Saccharomyces cerevisiae D4 was examined. However, again only one plate per concentration was used and the validity of the positive control was doubtful. Due to these methodological deficiencies, both studies were not considered for assessment of mutagenic potential.

In summary, 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate is not considered to have mutagenic potential in bacteria.

CAS 97281-24-8

The mutagenic potential of Fatty acids, C8-10, mixed esters with neopentyl glycol and trimethylolpropane (CAS# 97281-24-8) was tested in a reverse mutation assay comparable to OECD Guideline 471 and under GLP conditions (Banduhn, 1988). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 were used. Tester strains were incubated with test material dissolved in Tween 80/water at concentrations of 8, 40, 200, 1000 and 5000 µg/plate with and without the addition of a metabolic activation system (Aroclor 1254 induced rat liver S9 mix). Vehicle and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent vehicle controls was observed in all strains treated with the test substance, neither in the presence nor in the absence of metabolic activation. No cytotoxicity was observed. Thus, Fatty acids, C8-10, mixed esters with neopentyl glycol and trimethylolpropane did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested.

CAS 91050-89-4

The mutagenic potential of Fatty acids, C8-10, triesters with trimethylolpropane (CAS# 91050-89-4) was tested in a reverse mutation assay comparable to OECD Guideline 471 and under GLP conditions (Banduhn, 1993Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 were used. Tester strains were incubated with test material dissolved in Tween 80 and water at concentrations of 8, 40, 200, 1000 and 5000 µg/plate with and without the addition of a metabolic activation system (Arochlor 1254 induced rat liver S9 mix). Vehicle, negative and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent controls was observed in all strains treated with the test substance, neither in the presence nor in the absence of metabolic activation. No cytotoxicity was observed, but the test substance was tested up to precipitating concentrations. Thus, Fatty acids, C8-10, triesters with trimethylolpropane did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested.

CAS 85186-89-6

The mutagenic potential of Fatty acids, C8-18 and C18-unsatd., esters with trimethylolpropane (CAS# 85186-89-6) was examined in a reverse mutation assay comparable to OECD Guideline 471 and under GLP conditions (Wiebel, 1999). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 were used. Tester strains were incubated with test material dissolved in acetone at concentrations of 8, 40, 200, 1000 and 5000 µg/plate (no toxicity but tested up to precipitating concentrations) with and without the addition of a metabolic activation system (phenobarbitale and beta-naphthoflavone induced rat liver S9 mix). Vehicle, negative and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent controls was observed in all strains treated with the test substance, neither in the presence nor in the absence of metabolic activation. No cytotoxicity was observed but the test substance was tested up to limit concentrations. Thus, Fatty acids, C8-18 and C18-unsatd., esters with trimethylolpropane did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested.

CAS 403507-18-6

The mutagenic potential of Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS# 403507-18-6) was tested in a reverse mutation assay comparable to OECD Guideline 471 and under GLP conditions (Bowles, 2002). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA102 were used. Tester strains were incubated with test material dissolved in acetone at concentrations of 50, 150, 500, 1500 and 5000 µg/plate with and without the addition of a metabolic activation system (phenobarbitale and beta-naphthoflavone induced rat liver S9 mix). Vehicle and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent vehicle controls was observed in all strains treated with the test substance, neither in the presence nor in the absence of metabolic activation. No cytotoxicity was observed, but the test substance was tested up to precipitating concentrations. Thus, Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested.

CAS 85116-93-4

The mutagenic potential of Fatty acids, C16-18, esters with pentaerythritol (CAS# 85116-93-4) was tested in a reverse mutation assay comparable to OECD Guideline 471 and under GLP conditions (Banduhn, 1991). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 were used. Tester strains were incubated with test material dissolved in Tween 80 at concentrations of 8, 40, 200, 1000 and 5000 µg/plate (no toxicity but tested up to precipitating concentrations) with and without the addition of a metabolic activation system (Aroclor 1254 induced rat liver S9 mix). Vehicle, negative and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent controls was observed in all strains treated with the test subsatnce, neither in the presence nor in the absence of metabolic activation. Thus, Fatty acids, C16-18, esters with pentaerythritol did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested.

CAS 67762-53-2

The mutagenic potential of Fatty acids, C5-9, tetraesters with pentaerythritol (CAS# 67762-53-2) was tested in a reverse mutation assay according to OECD Guideline 471 and under GLP conditions (Mecchi, 1999). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and E. coli WP2 uvrA were used. Tester strains were incubated with test material dissolved in ethanol at concentrations of 33.3, 100, 333, 1000, 3330 and 5000 µg/plate with and without the addition of a metabolic activation system (Aroclor 1254 induced rat liver S9 mix). Vehicle and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent negative controls was observed in all strains treated with the test material, neither in the presence nor in the absence of metabolic activation. Thus, Fatty acids, C5-9, tetraesters with pentaerythritol did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested.

CAS 68441-68-9

The mutagenic potential of Decanoic acid, mixed esters with octanoic acid and pentaerythritol (CAS# 68441-68-9) was tested in a reverse mutation assay according to OECD Guideline 471 and under GLP (Banduhn, 1991). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 were used. Tester strains were incubated with test material dissolved in Tween 80 at concentrations of 8, 40, 200, 1000 and 5000 µg/plate (no toxicity but tested up to precipitating concentrations) with and without the addition of a metabolic activation system (Arochlor 1254 induced rat liver S9 mix). Vehicle, negative and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent negative controls was observed in all strains treated with the test material, neither in the presence nor in the absence of metabolic activation. No cytotoxicity was observed but the test substance was tested up to limit concentrations. Thus, Decanoic acid, mixed esters with octanoic acid and pentaerythritol did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested.

CAS 85586-24-9

The mutagenic potential of Fatty acids, C8-10, tetraesters with pentaerythritol (CAS# 85586-24-9) was tested in a reverse mutation assay comparable to OECD Guideline 471 and under GLP conditions (Banduhn, 1991). Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 were used. Tester strains were incubated with the test material dissolved in Tween 80 at concentrations of 8, 40, 200, 1000 and 5000 µg/plate (no toxicity but tested up to the limit concentration) with and without the addition of a metabolic activation system (Aroclor 1254 induced rat liver S9 mix). Vehicle, negative and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent negative controls was observed in all strains treated with the test material, neither in the presence nor in the absence of metabolic activation. Thus, Fatty acids, C8-10, tetraesters with pentaerythritol did not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested.

CAS 189200-42-8

The mutagenic potential of Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS# 189200-42-8) was tested in a reverse mutation assay comparable to OECD Guideline 471 and under GLP conditions (Przygoda, 1995). The following Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA1538 were used. Tester strains were incubated with the test material dissolved in acetone at concentrations of 0.5, 5, 50, 500, 5000 µg/plate in the first experiment and 50, 100, 500, 1000 and 5000 µg/plate in the repeat experiment with and without the addition of a metabolic activation system (Arochlor 1254 induced rat liver S9 mix). Vehicle, negative and appropriate positive controls were included into the study design. Positive control materials induced statistically significant increases in the frequency of revertant colonies indicating the satisfactory performance of the test and the activity of the metabolizing system. No increase in the frequency of revertant colonies compared to concurrent negative controls was observed in all strains treated with the test material, neither in the presence nor in the absence of metabolic activation. No cytotoxicity was observed but beading of the test substance occured in the initial assay and repeat assay at 500 µg/plate and above with and without metabolic activation in all strains. Thus, Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritoland tripentaerythritoldid not induce point mutations by base-pair changes or frame-shifts in the genome of the strains tested.

In vitro cytogenicity in mammalian cells

CAS 68855-18-5

Testing according to OECD GUIDELINE 473 is still ongoing. The dossier will be updated as soon as possible and the Chemical Safety Assessment according to Annex I of Regulation (EC) No 1907/2006 will be re-evaluated based on the outcome of this new study.

CAS 85186-86-3

An in vitro mammalian chromosome aberration test was performed with Fatty acids, C8-18 and C18-unsatd., esters with neopentylglycol (CAS# 85186-86-3) in cultured peripheral human lymphocytes comparable to OECD Guideline 473 and under GLP conditions (Morris, 2012). Duplicate cultures of human lymphocytes were evaluated for chromosome aberrations in the presence and absence of metabolic activation (rat liver S9-mix). In the first experiment cells were exposed for 4 hours to the test substance dissolved in acetone at concentrations of 40, 80, 160, 320, 480, 640, 960, 1280 µg/mL with and without metabolic activation. In the second experiment cells were exposed for 24 hours without metabolic activation and for 4 hours with metabolic activation. The test substance did not induce cytotoxicity. A cloudy/oily precipitate was visible at 80 µg/mL and above with metabolic activation and at 160 µg/mL without metabolic activation. Vehicle (solvent) controls induced aberration frequencies within the range expected for normal human lymphocytes. Mitomycin C and Cyclophosphamide were used as positive control substances inducing statistically significant increases in aberration frequencies indicating the satisfactory performance of the test and of the activity of the metabolizing system. Evaluation of 100 well-spread metaphase cells from each culture for structural chromosomal aberrations revealed no increase in the frequency of chromosome aberrations and polyploid cells at any dose level tested in comparison to the negative controls. The test material was therefore considered to be non-clastogenic to human lymphocytes in vitro.

CAS 189120-64-7

An in vitro mammalian chromosome aberration test was performed with Fatty acids, C7-8, triesters with trimethylolpropane (CAS# 189120-64-7) in Chinese Hamster Ovary cells (CHO) according to OECD Guideline 473 and under GLP conditions (Chirdon, 2000). Duplicate cultures of CHO cells were evaluated for chromosome aberrations in the presence and absence of metabolic activation (Arochlor 1254 induced rat liver S9-mix). A range-finder toxicity test was conducted and the test item was tested at the following doses 20, 39, 78, 156, 313, 625, 1250 and 2500 µg/mL (3 h treatment), with and without S9. In the main experiments, cells were exposed for 3 hours with and without metabolic activation.. The test substance was dissolved in acetone and used at concentrations of 75, 250, 2500 µg/mL without metabolic activation and 25, 250, 2500 µg/mL in acetone with metabolic activation. Cytotoxicity was observed at the highest dose tested regardless of metabolic activation. Vehicle (solvent) controls induced aberration frequencies within the range expected. 9,10-Dimethylbenzanthracene and 1-Methyl-3-Nitro-1-Nitrosoguanidine were used as positive control materials inducing statistically significant increases in aberration frequencies indicating the satisfactory performance of the test and of the activity of the metabolizing system. Evaluation of 100 well-spread metaphase cells from each culture for structural chromosomal aberrations revealed no increase in the frequency of chromosome aberrations at any dose level tested in comparison to the negative controls. The test material was therefore considered to be non-clastogenic to CHO cells in vitro.

CAS 11138-60-6

An in vitro mammalian chromosome aberration test was performed with Decanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol octanoate (CAS# 11138-60-6) in Chinese Hamster Ovary cells (CHO) according to OECD Guideline 473 and under GLP conditions (Gudi, 1996). Duplicate cultures of CHO cells were evaluated for chromosome aberrations in the presence and absence of metabolic activation (Arochlor 1254 induced rat liver S9-mix). Cells were exposed for 4 and 20 hours without and for 4 hours with metabolic activation. The test substance was dissolved in ethanol and used at concentrations of 625, 1250, 2500, 5000 µg/mL. Cytotoxicity was observed at the highest dose tested regardless of metabolic activation. Mitomycin C and cyclophosphamide was used as positive control without and withmetabolic activation respectively. Vehicle (solvent) controls induced aberration frequencies within the range expected. Positive control material induced statistically significant increases in aberration frequencies indicating the satisfactory performance of the test and of the activity of the metabolizing system. Evaluation of 200 well-spread metaphase cells from each culture for structural chromosomal aberrations revealed no increase in the frequency of chromosome aberrations at any dose level tested in comparison to the negative controls. The test material was therefore considered to be non-clastogenic to CHO cells in vitro.

CAS 403507-18-6

An in vitro mammalian chromosome aberration test was performed with Fatty acids, C16-18 and C18-unsatd., branched and linear ester with trimethylolpropane (CAS# 403507-18-6) in cultured peripheral human lymphocytes comparable to OECD Guideline 473 and under GLP conditions (Durward, 2004). Duplicate cultures of human lymphocytes were evaluated for chromosome aberrations in the presence and absence of metabolic activation (rat liver S9-mix). In the first experiment cells were exposed for 4 hours to the test substance dissolved in acetone at concentrations of 240, 320, 400 µg/mL with and without metabolic activation. In the second experiment cells were exposed for 4 hours to 240, 320, 400 µg/mL with metabolic activation and for 24 hours to 240, 320, 400 µg/mL followed by 24 hours expression time without metabolic activation. The test substance did not induce cytotoxicity but a cloudy precipitate was already visible at 40 µg/mL. Vehicle (solvent) controls induced aberration frequencies within the range expected for normal human lymphocytes. Mitomycin C and Cyclophosphamide were used as positive control materials inducing statistically significant increases in aberration frequencies indicating the satisfactory performance of the test and of the activity of the metabolizing system. Evaluation of 200 well-spread metaphase cells from each culture for structural chromosomal aberrations revealed no increase in the frequency of chromosome aberrations and polyploid cells at any dose level tested in comparison to the negative controls. The test material was therefore considered to be non-clastogenic to human lymphocytes in vitro.

CAS 189200-42-8

An in vitro mammalian chromosome aberration test was performed with Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS# 189200-42-8) in Chinese hamster ovary cells (CHO cells) comparable to OECD Guideline 473 and under GLP conditions (Przygody, 1995). Duplicate cultures of CHO cells were evaluated for chromosome aberrations in the presence and absence of metabolic activation (rat liver S9-mix). In the first experiment, cells were exposed to the test substance for 3 hours and for 16 hours followed by 16 hours expression time with and without metabolic activation, respectively. The test substance was dissolved in acetone and used at concentrations of 40, 80 and 160 µg/mL. In the second experiment cells were again exposed for 3 hours and for 16 hours followed by 16 hours expression time with and without metabolic activation, respectively. Additionally, cells were exposed for 3 and 16 hours followed by 40 hours expression time with and without metabolic activation, respectively. The same substance concentrations as in first experiment were used. The test substance did not induce cytotoxicity but a precipitate was visible in the second experiment at 160 µg/mL after 16 hours incubation without metabolic activation. Vehicle (solvent) controls induced aberration frequencies within the range expected for normal human lymphocytes. N-Methyl-N-Nitro-N-Nitrosoguanidine and 7,12-Dimethylbenz[a]anthracene were used as positive control materials inducing statistically significant increases in aberration frequencies indicating the satisfactory performance of the test and of the activity of the metabolizing system. Evaluation of 100 well-spread metaphase cells from each culture for structural chromosomal aberrations revealed no increase in the frequency of chromosome aberrations and polyploid cells at any dose level tested in comparison to the negative controls. The test material was therefore considered to be non-clastogenic to CHO cells in vitro.

In vitro gene mutation in mammalian cells

CAS 68855-18-5

Testing according to OECD GUIDELINE 476 is still ongoing. The dossier will be updated as soon as possible and the Chemical Safety Assessment according to Annex I of Regulation (EC) No 1907/2006 will be re-evaluated based on the outcome of this new study.

CAS 42222-50-4

An in vitro Mammalian Cell Gene Mutation Assay according to OECD Guideline 476 and GLP was performed with 2,2-dimethyl-1,3-propanediyldioleate (CAS# 42222-50-4) in mouse lymphoma L5178Y cells (Flügge, 2012). The cells were treated for 3 hours with and without S9-mix in the first experiment, for 24 hours without S9 mix in the second experiment and again for 3 hours with S9 mix in the third experiment. The test substance was tested at 312.5, 625, 1250, 2500 and 5000 μg/mL. 3-Methylcholanthrene and Methylmethanesulfonate were used as positive controls with and without S9 mix, respectively. No toxicity was observed and all dose levels were evaluated in the absence and presence of S9-mix. Positive and negative controls were valid and in range of historical control data. No significant increase in the mutation frequency at the TK locus was observed after treatment with the test substance either in the absence or in the presence of S9-mix. Thus, it was concluded that 2,2-dimethyl-1,3-propanediyldioleate is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions described.

CAS 85186-89-6

An in vitro Mammalian Cell Gene Mutation Assay according to OECD Guideline 476 and GLP was performed with Fatty acids, C8-18 and C18-unsatd., esters with trimethylolpropane (CAS# 85186-89-6) in mouse lymphoma L5178Y cells (Verspeek-Rip, 2010). The cells were treated for 3 and 24 hours with 8% (v/v) and without S9-mix in the first experiment, respectively, and with 12% (v/v) with and without S9-mix in the second experiment, respectively. In the first experiment the test substance was tested at 0.3, 1, 3, 10, 33, 100, 333 and 750 μg/mL up to precipitation with 8% (v/v) and without S9-mix for 3 h. In the second experiment the test substance was tested at 0.3, 1, 3, 10, 33, 100, 333 and 750 μg/mL up to precipitation with 12% (v/v) for 3 hours and without S9-mix for 24 hoursCyclophosphamide and Methylmethanesulfonate were used as positive controls with and without S9 mix, respectively. No toxicity was observed and all dose levels were evaluated in the absence and presence of S9-mix. Positive and negative controls were valid and in range of historical control data. No significant increase in the mutation frequency at the TK locus was observed after treatment with the test substance either in the absence or in the presence of S9-mix. It was concluded that Fatty acids, C8-18 and C18-unsatd., esters with trimethylolpropane is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions described.

CAS 15834-04-5

An in vitro Mammalian Cell Gene Mutation Assay according to OECD Guideline 476 and GLP was performed with 2,2-bis[[(1-oxopentyl)oxy]methyl]propane-1,3-diyl divalerate (CAS# 15834-04-5) in mouse lymphoma L5178Y cells (Verspeek-Rip, 2010). In the first experiment, the cells were treated for 3 hours with 0.03, 0.1, 0.3, 1, 3, 10, 33, 100 µg/mL in the presence or absence of S9-mix (8% (v/v)) . In the second experiment, test concentrations of 0.03, 0.1, 0.3, 1, 3, 10, 33, 100 µg/mL were applied with metabolic activation (12%, v/v) for 3 h and 0.1, 1, 3, 10, 33, 100, 200, 250 µg/mL without metabolic activation for 24 hours. The test substance was tested up to precipitating concentrations (100 µg/mL and above). Cyclophosphamide and methylmethanesulfonate were used as positive controls with and without S9 mix, respectively. No toxicity was observed and all dose levels were evaluated in the absence and presence of S9-mix. Positive and negative controls were valid and in range of historical control data. No significant increase in the mutation frequency at the TK locus was observed after treatment with the test substance either in the absence or in the presence of S9-mix. It was concluded that 2,2-bis[[(1-oxopentyl)oxy]methyl]propane-1,3-diyl divalerate is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions described.

Conclusion for genetic toxicity

In summary, several studies are available to assess the mutagenic potential in bacteria within the polyol esters category all providing negative results. Furthermore, no cytogenicity in mammalian cells in-vitro and no mutagenicity in mammalian cells in-vitro were observed with members of the polyol ester scategory.

 In conclusion, all available and reliable in vitro studies conducted with polyol esterscategory members revealed no effects on genetic toxicity. 


Short description of key information:
In none of these studies mutagenicity in bacteria could be observed.
In none of these studies clastogenic effects in mammalian cells could be observed.
In none of these studies mutagenicity in mammalian cells could be observed.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint".Since the category concept is applied to the polyol esters, data gaps will be filled by interpolation, as part of a read across approach from a representative category member(s) to avoid unnecessary animal testing. Additionally, once the category concept is applied, substances will be classified and labelled on this basis. Therefore, based on the group concept, all 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.