Stearic acid, monoester with propane-1,2-diol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The gene mutation in bacteria (OECD 471) of Stearic acid, monoester with propane-1,2-diol (PGMS) was evaluated in a weight of evidence approach based on the studies available from expert evaluations of PGMS, propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol (EFSA 2018a; EFSA 2018b, CIR 2019). Negative results were obtained and a lack of mutagenic/ genotoxic potential is concluded for PGMS.

 

Propane-1,2-diol esters of fatty acids as well as propane-1,2-diol were evaluated as a food additive by EFSA in 2018 (EFSA 2018 a, b) and fatty acids was evaluated for the use in cosmetics by CIR in 2019 (CIR 2919). Data on the genotoxicity are part of the evaluations.

 

Regarding gene mutation in bacteria, studies with bacterial reverse mutation assay (Ames) is described for PGMS, propane-1,2-diol esters of fatty acids, stearate fatty acids and propane-1,2-diol. Tests were performed in Salmonella Typhimurium strains TA100, TA1535, TA1537, TA98, TA1538 and Escherichia coli WP2uvrA (except for propane.1,2 diol, where data on E. coli WP2 is missing) with data comparable to current standards (OECD Guideline 471). Negative results were obtained in all studies with and without addition of S9 mix (EFSA 2018a; EFSA 2018b, CIR 2019).

 

Regarding genotoxicity in mammalian cells chromosome aberration tests are available. For propane-1,2-diol esters of fatty acids a chromosome aberration test in Chinese hamster lung fibroblast cells was performed with negative results. No cytotoxic effects, nor clastogenic activity, was reported at concentrations up to 0.125 mg/ml (EFSA 2018a). Studies on genotoxicity in mammalian cells was also evaluated in chromosome aberration tests with two types of fatty acid stearates in Chinese hamster lung fibroblast cells and human lymphocytes, respectively, both with negative results (CIR 2019).

One study of mammalian cell gene mutation at the TK locus was performed with lithium stearate in mouse lymphoma L5178Y cells at concentrations up to 120 μg/ml with metabolic activation (80 μg/ml with MA). No genotoxic effects were found (CIR 2019).

 

All expert evaluations conclude no concern for genotoxicity for the evaluated compounds (EFSA 2018a; EFSA 2018b, CIR 2019).

 

Based on the studies available for Stearic acid, monoester with propane-1,2-diol (PGMS), propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol, a lack of mutagenic/ genotoxic potential is concluded for PGMS, using a weigh of evidence approach.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

other: Weight of evidence analysis based on expert reviews on hydrolysis products and structural analogues

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: based on expert group reviews

Justification for type of information:

PGMS is manufactured by a reaction between stearic acid and propylene glycol. The UVCB substance belongs to the group of fatty acid esters. Within this group is the group of polyglycerol fatty acid esters, which are commonly used in cosmetics and as food ingredients representing substances composed of chemical units of similar structure as the fatty acid esters with propylene glycol. The polyglycerol fatty acids are esters of fatty acids and units of glycerol. The glycerol units represent the propylene glycol in “Stearic acid, monoester with propane-1,2-diol”.

To assess the genotoxicity of the substance, the toxicity of propane-1,2-diol ester of fatty acids and fatty acids in general is therefore considered. As supplementary data, also studies reviewed on propane-1,2-diol is included. As propane-1,2-diol is a major component of the substance and as the substance contains fatty acids, read-across to data on these substances is considered acceptable for the present substance. In general, data on propane-1,2-diol ester of fatty acids (EFSA 2018a) and fatty acids (CIR 2019) will be used.

A weight of evidence document is attached. The conclusion in this document is based on data from the following expert assessments:

CIR (2015). Safety Assessment of Propylene Glycol Esters as Used in Cosmetics, Final Amended report, January 15, 2015.
CIR (2019). Safety Assessment of Fatty Acids & Fatty Acid Salts as Used in Cosmetics, Tentative Report for Public Commenting, January 4, 2019
EFSA (2018a). Re-evaluation of propane-1,2-diol esters of fatty acids (E 477) as a food additive EFSA Panel on Food Additives and Flavourings (FAF). EFSA Journal 2018;16(12):5497.
EFSA (2018b). Re-evaluation of propane-1,2-diol (E 1520) as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2018;16(4):5235

Principles of method if other than guideline:

In relation to the data requirements of REACH VIII (10-100 t/y), data on genetic toxicity must be provided. Detailed study reports on this endpoint is not available for Stearic acid, monoester with propane-1,2-diol (PGMS), however data on PGMS in expert reviews are available.

Metabolism studies of propane-1,2-diol esters of stearate show that the substances are partially hydrolysed by pancreatic lipase; approx. 70% in 15 h. As the passage through the small intestine has a duration of 6–8 h, unhydrolyzed propane-1,2-diol esters of stearate will be present in the gastrointestinal tract for absorption (EFSA 2018a).

The possible genetic toxicity of this substance is therefore assessed in the present weight of evidence analysis based on existing data on propane-1,2-diol esters of fatty acids including PGMS (EFSA 2018a) and the relevant hydrolysis products propane-1,2-diol (EFSA 2018b) and fatty acids (CIR 2019).

As the substance is an UVCB-substance and as expert group assessments of the components in the substances are considered the most valid data for the assessment, an overall weight of evidence approach based on these expert evaluations is used for the assessment.

Type of assay:

bacterial reverse mutation assay

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Conclusions:

The gene mutation in bacteria (OECD 471) of Stearic acid, monoester with propane-1,2-diol (PGMS) was evaluated in a weight of evidence approach based on the studies available from expert evaluations of PGMS, propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol (EFSA 2018a; EFSA 2018b, CIR 2019). Negative results were obtained and a lack of mutagenic/ genotoxic potential is concluded for PGMS.

Executive summary:

Stearic acid, monoester with propane-1,2-diol (PGMS) is a UVCB substance. The two main constituents of the UVCB substance are the monoester of propane-diol with octadecanoic acid (45-98%) and the monoester of propane-diol with palmitic acid (2-50%).

 

Limited studies on genotoxicity are available for Stearic acid, monoester with propane-1,2-diol (PGMS). Data were therefore also obtained for propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol in a weight of evidence approach. Propane-1,2-diol esters of fatty acids as well as propane-1,2-diol were evaluated as a food additive by EFSA in 2018 (EFSA 2018 a, b) and fatty acids was evaluated for the use in cosmetics by CIR in 2019 (CIR 2919).

 

Regarding gene mutation in bacteria, studies with bacterial reverse mutation assay (Ames) is described for PGMS, propane-1,2-diol esters of fatty acids, stearate fatty acids and propane-1,2-diol. Tests were performed in Salmonella Typhimurium strains TA100, TA1535, TA1537, TA98, TA1538 and Escherichia coli WP2uvrA (except for propane.1,2 diol, where data on E. coli WP2 is missing) with data comparable to current standards (OECD Guideline 471). Negative results were obtained in all studies with and without addition of S9 mix (EFSA 2018a; EFSA 2018b, CIR 2019).

 

All expert evaluations conclude no concern for genotoxicity for the evaluated compounds (EFSA 2018a; EFSA 2018b, CIR 2019). Thus, based on the studies available for PGMS, propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol, a lack of mutagenic/ genotoxic potential is concluded for PGMS, using a weight of evidence approach.

Reference 2

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

other: Weight of evidence analysis based on expert reviews on hydrolysis products and structural analogues

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: based on expert group reviews

Justification for type of information:

PGMS is manufactured by a reaction between stearic acid and propylene glycol. The UVCB substance belongs to the group of fatty acid esters. Within this group is the group of polyglycerol fatty acid esters, which are commonly used in cosmetics and as food ingredients representing substances composed of chemical units of similar structure as the fatty acid esters with propylene glycol. The polyglycerol fatty acids are esters of fatty acids and units of glycerol. The glycerol units represent the propylene glycol in “Stearic acid, monoester with propane-1,2-diol”.

To assess the genotoxicity of the substance, the toxicity of propane-1,2-diol ester of fatty acids and fatty acids in general is therefore considered. As supplementary data, also studies reviewed on propane-1,2-diol is included. As propane-1,2-diol is a major component of the substance and as the substance contains fatty acids, read-across to data on these substances is considered acceptable for the present substance. In general, data on propane-1,2-diol ester of fatty acids (EFSA 2018a) and fatty acids (CIR 2019) will be used.

A weight of evidence document is attached. The conclusion in this document is based on data from the following expert assessments:

CIR (2015). Safety Assessment of Propylene Glycol Esters as Used in Cosmetics, Final Amended report, January 15, 2015.
CIR (2019). Safety Assessment of Fatty Acids & Fatty Acid Salts as Used in Cosmetics, Tentative Report for Public Commenting, January 4, 2019
EFSA (2018a). Re-evaluation of propane-1,2-diol esters of fatty acids (E 477) as a food additive EFSA Panel on Food Additives and Flavourings (FAF). EFSA Journal 2018;16(12):5497.
EFSA (2018b). Re-evaluation of propane-1,2-diol (E 1520) as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2018;16(4):5235

Principles of method if other than guideline:

In relation to the data requirements of REACH VIII (10-100 t/y), data on genetic toxicity must be provided. Detailed study reports on this endpoint is not available for Stearic acid, monoester with propane-1,2-diol (PGMS), however data on PGMS in expert reviews are available.

Metabolism studies of propane-1,2-diol esters of stearate show that the substances are partially hydrolysed by pancreatic lipase; approx. 70% in 15 h. As the passage through the small intestine has a duration of 6–8 h, unhydrolyzed propane-1,2-diol esters of stearate will be present in the gastrointestinal tract for absorption (EFSA 2018a).

The possible genetic toxicity of this substance is therefore assessed in the present weight of evidence analysis based on existing data on propane-1,2-diol esters of fatty acids including PGMS (EFSA 2018a) and the relevant hydrolysis products propane-1,2-diol (EFSA 2018b) and fatty acids (CIR 2019).

As the substance is an UVCB-substance and as expert group assessments of the components in the substances are considered the most valid data for the assessment, an overall weight of evidence approach based on these expert evaluations is used for the assessment.

Type of assay:

in vitro mammalian chromosome aberration test

Specific details on test material used for the study:

The conclusion is based on a collection of data performed equivalent or similar to relevant guidelines. Please refer to attached weight of evidence document.

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Key result

Species / strain:

lymphocytes: human

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Key result

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Conclusions:

The genotoxicity of Stearic acid, monoester with propane-1,2-diol (PGMS) was evaluated in a weight of evidence approach based on the studies available from expert evaluations of PGMS, propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol (EFSA 2018a; EFSA 2018b, CIR 2019). Negative results were obtained and a lack of mutagenic/ genotoxic potential is concluded for PGMS.

Executive summary:

Stearic acid, monoester with propane-1,2-diol (PGMS) is a UVCB substance. The two main constituents of the UVCB substance are the monoester of propane-diol with octadecanoic acid (45-98%) and the monoester of propane-diol with palmitic acid (2-50%).

Limited studies on genotoxicity are available for Stearic acid, monoester with propane-1,2-diol (PGMS). Data were therefore also obtained for propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol in a weight of evidence approach. Propane-1,2-diol esters of fatty acids as well as propane-1,2-diol were evaluated as a food additive by EFSA in 2018 (EFSA 2018 a, b) and fatty acids was evaluated for the use in cosmetics by CIR in 2019 (CIR 2919).

Regarding genotoxicity in mammalian cells chromosome aberration tests are available. For propane-1,2-diol esters of fatty acids a chromosome aberration test in Chinese hamster lung fibroblast cells was performed with negative results. No cytotoxic effects, nor clastogenic activity, was reported at concentrations up to 0.125 mg/ml (EFSA 2018a). Studies on genotoxicity in mammalian cells was also evaluated in chromosome aberration tests with two types of fatty acid stearates in Chinese hamster lung fibroblast cells and human lymphocytes, respectively, both with negative results (CIR 2019).

One study of mammalian cell gene mutation at the TK locus was performed with lithium stearate in mouse lymphoma L5178Y cells at concentrations up to 120 μg/ml with metabolic activation (80 μg/ml with MA). No genotoxic effects were found (CIR 2019).

All expert evaluations conclude no concern for genotoxicity for the evaluated compounds (EFSA 2018a; EFSA 2018b, CIR 2019). Thus, based on the studies available for PGMS, propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol, a lack of mutagenic/ genotoxic potential is concluded for PGMS.

Reference 3

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

other: Weight of evidence analysis based on expert reviews on hydrolysis products and structural analogues

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: based on expert group reviews

Justification for type of information:

PGMS is manufactured by a reaction between stearic acid and propylene glycol. The UVCB substance belongs to the group of fatty acid esters. Within this group is the group of polyglycerol fatty acid esters, which are commonly used in cosmetics and as food ingredients representing substances composed of chemical units of similar structure as the fatty acid esters with propylene glycol. The polyglycerol fatty acids are esters of fatty acids and units of glycerol. The glycerol units represent the propylene glycol in “Stearic acid, monoester with propane-1,2-diol”.

To assess the genotoxicity of the substance, the toxicity of propane-1,2-diol ester of fatty acids and fatty acids in general is therefore considered. As supplementary data, also studies reviewed on propane-1,2-diol is included. As propane-1,2-diol is a major component of the substance and as the substance contains fatty acids, read-across to data on these substances is considered acceptable for the present substance. In general, data on propane-1,2-diol ester of fatty acids (EFSA 2018a) and fatty acids (CIR 2019) will be used.

A weight of evidence document is attached. The conclusion in this document is based on data from the following expert assessments:

CIR (2015). Safety Assessment of Propylene Glycol Esters as Used in Cosmetics, Final Amended report, January 15, 2015.
CIR (2019). Safety Assessment of Fatty Acids & Fatty Acid Salts as Used in Cosmetics, Tentative Report for Public Commenting, January 4, 2019
EFSA (2018a). Re-evaluation of propane-1,2-diol esters of fatty acids (E 477) as a food additive EFSA Panel on Food Additives and Flavourings (FAF). EFSA Journal 2018;16(12):5497.
EFSA (2018b). Re-evaluation of propane-1,2-diol (E 1520) as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2018;16(4):5235

Principles of method if other than guideline:

In relation to the data requirements of REACH VIII (10-100 t/y), data on genetic toxicity must be provided. Detailed study reports on this endpoint is not available for Stearic acid, monoester with propane-1,2-diol (PGMS), however data on PGMS in expert reviews are available.

Metabolism studies of propane-1,2-diol esters of stearate show that the substances are partially hydrolysed by pancreatic lipase; approx. 70% in 15 h. As the passage through the small intestine has a duration of 6–8 h, unhydrolyzed propane-1,2-diol esters of stearate will be present in the gastrointestinal tract for absorption (EFSA 2018a).

The possible genetic toxicity of this substance is therefore assessed in the present weight of evidence analysis based on existing data on propane-1,2-diol esters of fatty acids including PGMS (EFSA 2018a) and the relevant hydrolysis products propane-1,2-diol (EFSA 2018b) and fatty acids (CIR 2019).

As the substance is an UVCB-substance and as expert group assessments of the components in the substances are considered the most valid data for the assessment, an overall weight of evidence approach based on these expert evaluations is used for the assessment.

Type of assay:

sister chromatid exchange assay in mammalian cells

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

S9

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Key result

Species / strain:

hepatocytes: male rat

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Conclusions:

The genotoxicity of Stearic acid, monoester with propane-1,2-diol (PGMS) was evaluated in a weight of evidence approach based on the studies available from expert evaluations of PGMS, propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol (EFSA 2018a; EFSA 2018b, CIR 2019). Negative results were obtained and a lack of mutagenic/ genotoxic potential is concluded for PGMS.

Executive summary:

Stearic acid, monoester with propane-1,2-diol (PGMS) is a UVCB substance. The two main constituents of the UVCB substance are the monoester of propane-diol with octadecanoic acid (45-98%) and the monoester of propane-diol with palmitic acid (2-50%).

Limited studies on genotoxicity are available for Stearic acid, monoester with propane-1,2-diol (PGMS). Data were therefore also obtained for propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol in a weight of evidence approach. Propane-1,2-diol esters of fatty acids as well as propane-1,2-diol were evaluated as a food additive by EFSA in 2018 (EFSA 2018 a, b) and fatty acids was evaluated for the use in cosmetics by CIR in 2019 (CIR 2919).

Regarding genotoxicity in mammalian cells chromosome aberration tests are available. For propane-1,2-diol esters of fatty acids a chromosome aberration test in Chinese hamster lung fibroblast cells was performed with negative results. No cytotoxic effects, nor clastogenic activity, was reported at concentrations up to 0.125 mg/ml (EFSA 2018a). Studies on genotoxicity in mammalian cells was also evaluated in chromosome aberration tests with two types of fatty acid stearates in Chinese hamster lung fibroblast cells and human lymphocytes, respectively, both with negative results (CIR 2019).

One study of mammalian cell gene mutation at the TK locus was performed with lithium stearate in mouse lymphoma L5178Y cells at concentrations up to 120 μg/ml with metabolic activation (80 μg/ml with MA). No genotoxic effects were found (CIR 2019).

All expert evaluations conclude no concern for genotoxicity for the evaluated compounds (EFSA 2018a; EFSA 2018b, CIR 2019). Thus, based on the studies available for PGMS, propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol, a lack of mutagenic/ genotoxic potential is concluded for PGMS.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the studies available for Stearic acid, monoester with propane-1,2-diol” (PGMS), propane-1,2-diol esters of fatty acids, fatty acids in general and propane-1,2-diol, a lack of mutagenic/ genotoxic potential is concluded for PGMS, using a weight of evidence approach. Thus, no classification apply.