Reaction mass of propylidynetrimethanol and 2-ethylpropane-1,3-diol and 5-ethyl-1,3-dioxane-5-methanol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The genetic toxicity ofthe target substance Polyol TD was investigated in a bacterial reverse mutation assay (OECD Guideline 471). Polyol TD did not induce mutation frequency above background with and without metabolic activation.

In addition, data from in vitro genotoxicity testing battery (gene mutations and chromosomal aberrations in mammalian cells assays) conducted in accordance with OECD guidelines with suitable read-across partners, 2 -ethylpropane1,3 -diol (DMP) and 5 -Ethyl-1,3 -dioxane-5 -methanol (CTF) was used in a weight of evidence approach to assess the genotoxicity of the target substance.Mammalian gene mutation assays according to OECD Guideline 476 and chromosomal aberration assays according to OECD Guideline 473 with both DMP and CTF did not show evidence for genetic toxicity.

Based on the data from Polyol TD itself and read-across data from the source substances, it is concluded that Polyol TD does not cause genetic toxicity. Therefore, no further in vivo testing is required.

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-05-08 to 2008-09-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

21 July 1997

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

Version / remarks:

1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries. Test Data for Registration of Agricultural Chemicals, 12 Noshan No. 8417, Guideline 2-1-19-1, Agricultural Production Bureau

Version / remarks:

24 November 2000

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Official notice of J MHLW, METI and ME

Version / remarks:

21 November 2003

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: ICH Guideline S2A: Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals. PAB/PCD Notification No. 444.

Version / remarks:

1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: ICH Guideline S2B: Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals. PMSB/ELD Notification No. 5

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Includes MHRA GLP compliance certificate.

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material (as cited in study report): Polyol TD
- Physical state: Colourless liquid
- Analytical purity: Hydroxyl number, 760 mg KOH/g
- Lot/batch No.: 3777937
- Expiration date of the lot/batch: Indefinite
- Storage condition of test material: Room temperature in the dark, dry

Target gene:

his/trp operon

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain / cell type:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

5, 15, 50, 150, 500, 1500, 5000 µg/plate, first test.
50, 150, 500, 1500, 5000 µg/plate, second test.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water, purified in-house by reverse osmosis
- Justification for choice of solvent/vehicle: The Sponsor indicated that the test substance was miscible with water.

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

: purified water

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

In the absence of S9 mix: 2 µg/plate for strains TA100 and TA 1535

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

: purified water

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

In the absence of S9 mix: 50 µg/plate for strain TA1537

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

:purified water

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

In the absence of S9 mix: 2 µg/plate for strain TA98

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

: purified water

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

In the absence of S9 mix: 2 µg/plate for strain WP2 uvrA (pKM101)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

: purified water

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

In the presence of S9 mix: 5 µg/plate for strains TA 100 and TA 1535; 10 µg/plate for strain WP2 uvrA (pKM101)

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

: purified water

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

In the presence of S9 mix: 5 µg/plate for strains TA98 and TA 1537

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation) - first test; preincubation - second test

DURATION
- Preincubation period: 30 minutes at 37ºC (second test only).
- Exposure duration: Plates incubated for 72 hours
- Expression time (cells in growth medium): 10 hours


SELECTION AGENT (mutation assays): Histidine (Salmonella strains) and tryptophan (E Coli strain)

NUMBER OF REPLICATIONS: Three plates at each concentration in each test.

DETERMINATION OF CYTOTOXICITY
- Method: Any toxic effects of the test substance would be detected by a substantial reduction in mean revertant colony counts or by a sparse or absent backgroud bacterial lawn.


OTHER: all strains/cell types requested by OECD 471 tested

Evaluation criteria:

If exposure to a test substance produces a reproducible increase in revertant colony numbers of at least twice (three times in the case of strains TA1535 and TA1537) the concurrent vehicle controls, with some evidence of a positive dose-response relationship, it is considered to exhibit mutagenic activity in this test system. No statistical analysis is performed.
If exposure to a test substance does not produce a reproducible increase in revertant colony numbers, it is considered to show no evidence of mutagenic activity in this test system. No statistical analysis is performed.

Statistics:

If the results obtained fail to satisfy the criteria for a clear “positive” or “negative” response, even after additional testing, the test data may be subjected to analysis to determine the statistical significance of any increases in revertant colony numbers. The statistical procedures used are those described by Mahon et al (1989) and are usually Dunnett’s test followed, if appropriate, by trend analysis. Biological importance should always be considered along with statistical significance. In general, treatment-associated increases in revertant colony numbers below two or three times the vehicle controls (as described above) are not considered biologically important. It should be noted that it is acceptable to conclude an equivocal response if no clear results can be obtained.

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

First test:
No evidence of toxicity was obtained following exposure to Polyol TD. A maximum exposure concentration of 5000 μg/plate was, therefore, selected for use in the second test. No substantial increases in revertant colony numbers over control counts were obtained with any of the tester strains following exposure to Polyol TD at any concentration up to 5000 μg/plate in either the presence or absence of S9 mix.

Second test:
No evidence of toxicity was obtained following exposure to Polyol TD. No substantial increases in revertant colony numbers over control counts were obtained with any of the tester strains following exposure to Polyol TD at any concentration up to 5000 μg/plate in either the presence or absence of S9 mix.

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: Not reported.
- Effects of osmolality: Not reported.
- Evaporation from medium: Not reported.
- Water solubility: Not reported.
- Precipitation:Not reported.
- Other confounding effects: Not reported.


RANGE-FINDING/SCREENING STUDIES:
No evidence of toxicity was obtained following exposure to Polyol TD. A maximum exposure concentration of 5000 μg/plate was, therefore, selected for use in the second test.

COMPARISON WITH HISTORICAL CONTROL DATA:
The mean revertant colony counts for the vehicle controls were within or close to the 99% confidence limits of the current historical control range of the laboratory.

For further information and details on results, please refer to result tables, attached.

Conclusions:

Based on the results from this baterial reverse mutation assay (according to OECD Guideline 471), It is concluded that Polyol TD showed no evidence of mutagenic activity in all bacterial strains (S. typhimurium TA 98, TA 102, TA1535, TA 1537 and E. coli WP2 uvrA pkM 101) which were investigated under the test conditions.

Executive summary:

In a reverse gene mutation assay in bacteria performed according to OECD TG 471, strains TA 98, TA 102, TA1535 and TA 1537 of S. typhimurium and WP2 uvrA pkM 101 of E. coli were exposed to Polyol TD at concentrations of 5, 15, 50, 150, 500, 1500, 5000 µg/plate in the first test and 50, 150, 500, 1500, 5000 µg/plate in the second test in the presence and absence of mammalian metabolic activation by a rat liver homogenate fraction (S9 mix). In the first test, the plate co-incubation method was used, while in the second test, a pre-incubation with the test substance was performed.

Polyol TD was tested up to the limit concentration of 5000 µg/plate. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence or a concentration related response of induced mutant colonies over background. Based on the results, the test item can be considered to be non-mutagenic.

This study is calssified as acceptable as it satisfies the requirement for Test Guideline OPPTS 870.5100; OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.

Reference 2

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

No toxicity was noted in any of the cultures treated with CTF, when tested to a limit concentration of 1462 μg/mL.
Cultures treated with the following dose levels of CTF were selected for assessment of chromosomal aberrations: 366, 731 and 1462 μg/mL.
The vehicle control cultures had levels of structural and numerical aberrations within the 95% confidence limits of the historical negative control data. The positive control substances, cyclophosphamide in the presence and methyl methanesulphonate in the absence of S9 mix, induced positive frequencies of structural aberrations in at least one concentration level per section. These results demonstrated the sensitivity of the test system.
All cultures treated with CTF had levels of structural aberrations within the 95% confidence limits for a negative response. An extra assessment of polyploidy was carried out on the cultures treated in the absence of S9 mix and harvested at 48 h. All the cultures treated with CTF had levels of polyploidy within the 95% confidence limits for a negative response.

Conclusions:

It was concluded that CTF was not clastogenic when tested in Chinese hamster ovary cells up to recommended limit concentrations with and without metabolic activation in vitro.

Executive summary:

In a mammalian cell chromosomal aberration assay according to OECD Guideline 473, CHO cell cutures were exposed to CTF (cyclic trimethylolpropane formal) in culture medium at concentrations up to the limit dose of 1462 µg/mL (corresponding to 10 mM) in the first experiment and at concentrations of 183, 366, 731 and 1462 μg/mL in the second experiment with and without metabolic activation for 6 -24 hours (S9 post-mitochondrial supernatant fraction obtained from the livers of Aroclor 1254 -treated adult, male rats). Positive controls (methylmethanesulfonate without S9 -mix and cyclophosphamide with S9-mix) induced the appropriate response. There was no evidence or a concentration related positive response of chromosome aberration induced over background.

This study is classified as acceptable, as it satisfies the requirement for Test Guideline OECD 473 for in vitro cytogenetic mutagenicity data.

 

This information is used in a read-across approach in the assessment of the target substance. Fordetails andjustification of read-across please refer to the attached read-across report (see IUCLID section 13).

Reference 3

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

True negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

No toxicity was noted in any of the cultures treated with DMP Tech, when tested to a concentration of 1041 μg/mL.
Cultures treated with the following dose levels of DMP Tech were selected for assessment of chromosomal aberrations: 260, 521 and 1041 μg/mL.
The vehicle control cultures had levels of structural and numerical aberrations within the 95% confidence limits of the historical negative control data.
The positive control substances, cyclophosphamide in the presence and methyl methanesulphonate in the absence of S9 mix, induced positive frequencies of structural aberrations in at least one concentration level per section. These results demonstrated the sensitivity of the test system.
All cultures treated with DMP Tech had levels of structural aberrations within the 95% confidence limits for a negative response. An extra assessment of polyploidy was carried out on the cultures treated in the absence of S9 mix and harvested at 48 h. All the cultures treated with DMP Tech had levels of polyploidy within the 95% confidence limits for a negative response.

Conclusions:

It was concluded that DMP Tech was not clastogenic when tested in Chinese hamster ovary cells up to recommended limit concentrations with and without metabolic activation in vitro.

Executive summary:

In a mammalian cell chromosomal aberration assay according to OECD Guideline 473, CHO cell cutures were exposed to DMP Tech in culture medium at concentrations up to the limit dose of 1041 µg/mL (corresponding to 10 mM) in the first experiment and at concentrations of 130, 260, 521 and 1041 μg/mL in the second experiment with and without metabolic activation for 6 -24 hours (S9 post-mitochondrial supernatant fraction obtained from the livers of Aroclor 1254 -treated adult, male rats). Positive controls (methylmethanesulfonate without S9 -mix and cyclophosphamide with S9-mix) induced the appropriate response. There was no evidence or a concentration related positive response of chromosome aberration induced over background.

This study is classified as acceptable, as it satisfies the requirement for Test Guideline OECD 473 for in vitro cytogenetic mutagenicity data.

 

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Reference 4

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

The results of the toxicity tests show that CTF did not cause an appreciable reduction in cell growth at the predetermined maximum concentration of 1462 μg/mL (10 mM) in either the 4 h exposure system (absence and presence of S9 mix) or the 24 h exposure system.
The solvent control mean mutant fractions were within the normal ranges experienced in the test laboratory and reported in the literature. All positive control log mutant fractions were significantly higher than the vehicle controls at P<0.05.

Assays 1 and 2: 4 h exposure with and without S9
None of the assessed concentrations tested significant for increase in log mutant fraction in either experiment. In the absence of S9 mix, the test for linear trend was not significant (P = 0.72), while in the presence of S9 mix the test for linear trend was not reported as the slope was negative. There was no toxicity at any concentration of CTF in either experiment. Both experiments were classed as negative.

Assays 3 and 4: 24 h exposure without S9, 4 h exposure with S9
In the absence of S9 mix, the overall mutant (Hm) heterogeneity factor was statistically significantly higher than the historical control and therefore no statistical analysis was reported for this assay. The mutant fractions obtained with CTF were all very close to the vehicle control value and it can be assumed that no mutagenic activity was present in these cultures. In the presence of S9 mix, none of the assessed concentrations tested significant for increase in log mutant fraction and the test for linear trend was not significant (P = 0.70). CTF was not toxic in either experiment.
Both experiments were classified negative.

A combined statistical analysis of Assays 2 and 4 (where all treatment conditions and concentrations of test item were identical) was made. There were no statistically significant differences between the CTF-treated groups and the vehicle controls. The test for linear trend was not reported as the slope was negative.

Conclusions:

It was concluded that CTF is not mutagenic in a mammalian cell gene mutation assay (according to OECD Guideline 476), using mouse lymphoma L5178Y cells, in either the absence or the presence of S9 mix, when tested to the pre-determined maximum concentration of 1462 μg/mL (10 mM).

Executive summary:

In a mammalian cell gene mutation assay at the Thymidine kinase locus (Tk+/-) (according to OECD Guideline 476), mouse lymphoma L5178Y cells (clone -3.7.2C) cultured in vitro were exposed to CTF in culture medium at concentrations of 183, 366, 731 and 1462 µg/mL (corresponding to 10 mM), employing exposure times of 4 h (with and without S9) and 24 h (without S9) in the presence and absence of mammalian metabolic activation (S9 post-mitochondrial supernatant fraction obtained from Aroclor 1254-induced livers of adult male rats). CTF was tested up to limit concentrations of 10 mM. The positive controls (methylmethanesulfonate/ethylmethanesulfonate without S9 and 3 -methylcholanthrene with S9) did induce the appropriate response. There was no evidence or a concentration related positive response of induced mutant colonies over background.

This study is classified as acceptable, as it satisfies the requirement for Test Guideline OECD 476 for in vitro mutagenicity (mammalian forward gene mutation) data.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Reference 5

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

GLP compliance:

yes

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Remarks:

(cytotoxicity in some assays)

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

True negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

Toxicity Tests: When exposed to the cells for a period of 4 h in the absence of S9, the predetermined maximum concentration of 1041 μg/ml (10 mM) DMP Tech reduced suspension growth to 70.2% of the vehicle control value. In the presence of S9, 1041 μg/ml reduced relative suspension growth to 45.9%. When the exposure period in the absence of S9 was increased to 24 h, 1041 μg DMP Tech/ml reduced suspension growth to 45% of the vehicle control value.

Vehicle controls: With one exception, the solvent control mean mutant fractions were within the normal ranges experienced in the laboratory. The exception was Assay 3 (24 h exposure in the absence of S9 mix), where the mean of 49 mutants per million viable cells was slightly below the present range of 51-129. A value between 40 and 50 mutants per million is accepted providing the positive control group (MMS) is unequivocally acceptable. This being the case, the value was accepted.
Positive controls: All positive control log mutant fractions were significantly higher than the vehicle controls at P<0.05.

Assays 1 and 2, 4 h exposure: None of the assessed concentrations tested significant for increases in log mutant fractions with or without S9 mix. Both tests for linear trend were not significant (P = 0.46 in the absence of S9 mix; P = 0.37 in the presence of S9 mix). The RTG at the predetermined maximum concentration of 1041 μg/mL (10 mM) was 64% in the absence of S9 mix and 41% in the presence of S9 mix.

Assays 3 and 4, 24 h exposure: None of the assessed concentrations tested significant for increases in log mutant fractions with or without S9 mix. In the absence of S9 mix, the test for linear trend showed a low level of significance (P = 0.011). This was dismissed as coincidence as the largest increase in mutant fraction was only 40 mutants per million above the vehicle control group and the mutant fraction at that concentration (88 mutants per million) was well within the normal vehicle control range of 51-129 and was also within the mean +1 standard deviation of the historical
vehicle control range. In the presence of S9 mix the test for linear trend was not significant (P = 0.73). In the absence of S9 mix, the RTG at the predetermined maximum concentration of 1041 μg/mL (10 mM) was 16% (a definitive level of toxicity). In the presence of S9 mix, the RTG at 1041 μg/mL was 60%.

A combined statistical analysis of Assays 2 and 4 (where all treatment conditions and concentrations of test item were identical, with S9) was made. There were no statistically significant differences between the DMP Tech-treated groups and the vehicle controls. The test for linear trend was not significant (P = 0.40).

Conclusions:

It was concluded that DMP Tech is not mutagenic in a mammalian cell gene mutation assay (according to OECD Guideline 476), using mouse lymphoma L5178Y cells, in either the absence or the presence of S9 mix, when tested to the predetermined maximum concentration of 1041 μg/mL (10 mM). In addition, it was concluded that DMP Tech is not mutagenic in the absence of S9 mix with an extended 24 h exposure period, when tested at concentrations extending into the toxic range.

Executive summary:

In a mammalian cell gene mutation assay at the Thymidine kinase locus (Tk+/-) (according to OECD Guideline 476), mouse lymphoma L5178Y cells (clone -3.7.2C) cultured in vitro were exposed to DMP Tech (82.2%) in culture medium at concentrations of 125, 250, 500 and 1041 µg/ml (corresponding to 10 mM), employing exposure times of 4 h (with and without S9) and 24 h (without S9) in the presence and absence of mammalian metabolic activation (S9 post-mitochondrial supernatant fraction obtained from Aroclor 1254-induced livers of adult male rats). DMP Tech was tested up to limit concentrations of 10 mM. The positive controls (methylmethanesulfonate/ethylmethanesulfonate without S9 and 3 -methylcholanthrene with S9) did induce the appropriate response.

The only significant finding was a low level linear trend of mutant fraction with concentration of DMP Tech in the experiment conducted in the absence of S9 mix with a 24 h exposure (Assay 3). This result was dismissed as coincidence, as the increases recorded throughout the concentrations were very small and the mutant fractions were all comparable to normal vehicle control values. There was no other evidence or a concentration related positive response of induced mutant colonies over background in any of the 4 assays.

This study is classified as acceptable, as it satisfies the requirement for Test Guideline OECD 476 for in vitro mutagenicity (mammalian forward gene mutation) data.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Based on the results from in vitro experiments, further in vivo testing is not required according to Regulation (EC) No. 1907/2006.

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

 The genetic toxicity of Polyol TD (the Reaction mass of 2-ethylpropane-1,3-diol (DMP) and 5-ethyl-1,3-dioxane-5-methanol (CTF) and propylidynetrimethanol (TMP)) is adequately charecterised using a combination of studies on the substance itself and from a read-across approach with its components.

 

A negative Ames test is reported for Polyol TD (May, 2010). Negative results are reported from read-across with the components CTF and DMP in studies of clastogenicity in CHO cells in vitro (Murie, 2010); negative results are also reported for the components CTF and DMP in mouse lymphoma assays (Riach, 2010). All studies were performed in compliance with GLP and the according to the relevant guidelines and involved testing up to the respective limit concentrations.

 

The available studies therefore adequately demonstrate the absence of genotoxicity of Polyol TD (the Reaction mass of 2-ethylpropane-1,3-diol (DMP) and 5-ethyl-1,3-dioxane-5-methanol (CTF) and propylidynetrimethanol (TMP)). Read-across is proposed from DMP to the other component, TMP.No further studies are therefore required.

Justification for classification or non-classification

Based on the available results, the target substance is not considered to be genotoxic and no classification is warranted in accordance with CLP Regulation 1272/2008.