Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No studies on genotoxicity are available for “Reaction product of saturated palm kernel fatty acids and oxybispropanediol”. Data were therefore obtained for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance.

Glycerol, fatty acids, di- and tri-glycerols as well as polyglycerols of fatty acid ester were evaluated as a food additive by EFSA in 2017 (EFSA 2017 a, b, c, d). Data on the genotoxicity is presented as part of the evaluation.

Regarding gene mutation in bacteria, studies with bacterial reverse mutation assay (Ames) is described in Salmonella Typhimurium strains TA100, TA1535, TA1537, TA98, TA1538 and Escherichia coli WP2uvrA with data comparable to current standards (OECD Guideline 471). Negative results were obtained in all studies with and without addition of S9 mix (EFSA 2017a, b, c).

Studies on genotoxicity in mammalian cells was evaluated in chromosome aberration test in Chinese hamster lung fibroblast cells and in a HGPRT gene mutation assay CHO cells were performed, both with negative results. Also, a study on sister chromatid exchange and unscheduled DNA synthesis was described. No cytotoxic effects, nor clastogenic activity, was reported in the studies, where the highest concentration used was 92 mg/ml, a dose level 18 times greater than the maximum dose level recommended in vitro by OECD Guideline no. 473. EFSA concluded that the available studies were sufficient for evaluation of this endpoint and indicating no clastogenic activity of glycerol in in vitro studies (EFSA 2017a, c).

EFSA (2017d) found no structural alerts for genotoxicity of polyglycerol esters of fatty acids based on their own QSAR analysis for this end-point and present predictions of mutagenicity in silico for oxybispropanediol, capric, lauric, myristic, palmitic and stearic was also negative.

One study on a polyglycerol fatty acid ester was positive in in vitro chromosomal aberration study in Chinese hamster V79 cells, however, when retested in human peripheral blood lymphocytes, the results were negative both in the absence and presence of S9 metabolic activation. As all other studies are negative, and the positive result could not be repeated, it is evaluated that also polyglycerol fatty esters are not genotoxic (EFSA 2017d).

Based on the studies available for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential is concluded for "Reaction product of saturated palm kernel fatty acids and oxybispropanediol".

Link to relevant study records

Referenceopen allclose all

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:
No studies are available for Reaction product of saturated palm kernel fatty acids and oxybispropanediol. Data were therefore obtained for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and structural analogues.

Reaction product of saturated palm kernel fatty acids and oxybispropanediol is an UVCB substance, manufactured by a reaction between saturated palm kernel oil fatty acids with diglycerol. The UVCB substance belongs to the group of polyglyceryl fatty acid esters, which are commonly used in cosmetics and as food ingredients.

In general, data from the following expert assessments evaluating polyglyceryl fatty acids esters, glycerol, fatty acids and mono- and di-glycerides of fatty acids are used in a weight of evidence approach:
 
CIR. Safety Assessment of Polyglyceryl Fatty Acid Esters as Used in Cosmetics, Final report, November 14, 2016
EFSA (2017a). Re-evaluation of glycerol (E 422) as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(3):4720.
EFSA (2017b). Re-evaluation of fatty acids (E 570) as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(5):4785
EFSA (2017c). Re-evaluation of mono- and di-glycerides of fatty acids (E 471) as food additives. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(11):5045
EFSA (2017d). Re-evaluation of polyglycerol esters of fatty acids (E 475) as a food additive. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(12):5089
Principles of method if other than guideline:
The conclusion is based on a collection of data performed equivalent or similar to relevant guidelines. Please refer to attached weight of evidence document.
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:
Based on the studies available for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential is concluded for Reaction product of saturated palm kernel fatty acids and oxybispropanediol.
Executive summary:

No studies are available for Reaction product of saturated palm kernel fatty acids and oxybispropanediol. Data were therefore obtained for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance.

Glycerol, fatty acids, di- and tri-glycerols as well as polyglycerols of fatty acid ester were evaluated as a food additive by EFSA in 2017. Data on the genotoxicity is presented as part of the evaluation.

Studies on gene mutation in mammalian cells was investigated in a HGPRT gene mutation assay, sister chromatid exchange study and unscheduled DNA synthesis, all with negative results. No cytotoxic effects was reported in the studies.

EFSA (2017d) found no structural alerts for genotoxicity of polyglycerol esters of fatty acids based on their own QSAR analysis for this end-point and present predictions of mutagenicity in silico for oxybispropanediol, capric, lauric, myristic, palmitic and stearic was also negative.

Based on the studies available for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential is concluded for "Reaction product of saturated palm kernel fatty acids and oxybispropanediol".

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:
No studies are available for Reaction product of saturated palm kernel fatty acids and oxybispropanediol. Data were therefore obtained for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and structural analogues.

Reaction product of saturated palm kernel fatty acids and oxybispropanediol is an UVCB substance, manufactured by a reaction between saturated palm kernel oil fatty acids with diglycerol. The UVCB substance belongs to the group of polyglyceryl fatty acid esters, which are commonly used in cosmetics and as food ingredients.

In general, data from the following expert assessments evaluating polyglyceryl fatty acids esters, glycerol, fatty acids and mono- and di-glycerides of fatty acids are used in a weight of evidence approach:
 
CIR. Safety Assessment of Polyglyceryl Fatty Acid Esters as Used in Cosmetics, Final report, November 14, 2016
EFSA (2017a). Re-evaluation of glycerol (E 422) as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(3):4720.
EFSA (2017b). Re-evaluation of fatty acids (E 570) as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(5):4785
EFSA (2017c). Re-evaluation of mono- and di-glycerides of fatty acids (E 471) as food additives. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(11):5045
EFSA (2017d). Re-evaluation of polyglycerol esters of fatty acids (E 475) as a food additive. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(12):5089
Principles of method if other than guideline:
The conclusion is based on a collection of data performed equivalent or similar to relevant guidelines. Please refer to attached weight of evidence document.
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:
ambiguous
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Conclusions:
Based on the studies available for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential is concluded for Reaction product of saturated palm kernel fatty acids and oxybispropanediol.
Executive summary:

No studies are available for Reaction product of saturated palm kernel fatty acids and oxybispropanediol. Data were therefore obtained for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance.

Glycerol, fatty acids, di- and tri-glycerols as well as polyglycerols of fatty acid ester were evaluated as a food additive by EFSA in 2017 (EFSA 2017 a,b,c,d). Data on the genotoxicity is presented as part of the evaluation.

Cytogenicity in mammalian cells was investigated in chromosome aberration test in Chinese hamster lung fibroblast cells with negative results where the highest concentration used was 92 mg/ml, a dose level 18 times greater than the maximum dose level recommended in vitro by OECD Guideline no. 473. EFSA concluded that the available studies were sufficient for evaluation of this endpoint and indicating no clastogenic activity of glycerol in in vitro studies (EFSA 2017a, c).

EFSA (2017d) found no structural alerts for genotoxicity of polyglycerol esters of fatty acids based on their own QSAR analysis for this end-point and present predictions of mutagenicity in silico for oxybispropanediol, capric, lauric, myristic, palmitic and stearic was alsonegative.

One study on a polyglycerol fatty acid ester was positive in vitro chromosomal aberration study in Chinese hamster V79 cells, however, when retested in human peripheral blood lymphocytes, the results were negative both in the absence and presence of S9 metabolic activation. As all other studies are negative, and the positive result could not be represented, it is evaluated that also polyglycerol fatty esters are not genotoxic (EFSA 2017d).

 

Based on the studies available for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential is concluded for "Reaction product of saturated palm kernel fatty acids and oxybispropanediol".

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:
No studies are available for Reaction product of saturated palm kernel fatty acids and oxybispropanediol. Data were therefore obtained for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and structural analogues.

Reaction product of saturated palm kernel fatty acids and oxybispropanediol is an UVCB substance, manufactured by a reaction between saturated palm kernel oil fatty acids with diglycerol. The UVCB substance belongs to the group of polyglyceryl fatty acid esters, which are commonly used in cosmetics and as food ingredients.

In general, data from the following expert assessments evaluating polyglyceryl fatty acids esters, glycerol, fatty acids and mono- and di-glycerides of fatty acids are used in a weight of evidence approach:
 
CIR. Safety Assessment of Polyglyceryl Fatty Acid Esters as Used in Cosmetics, Final report, November 14, 2016
EFSA (2017a). Re-evaluation of glycerol (E 422) as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(3):4720.
EFSA (2017b). Re-evaluation of fatty acids (E 570) as a food additive EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(5):4785
EFSA (2017c). Re-evaluation of mono- and di-glycerides of fatty acids (E 471) as food additives. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(11):5045
EFSA (2017d). Re-evaluation of polyglycerol esters of fatty acids (E 475) as a food additive. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). EFSA Journal 2017;15(12):5089
Principles of method if other than guideline:
The conclusion is based on a collection of data performed equivalent or similar to relevant guidelines. Please refer to attached weight of evidence document.
Type of assay:
bacterial reverse mutation assay
Key result
Species / strain:
S. typhimurium, other: TA100, TA1535, A1537, TA98, TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Conclusions:
Based on the studies available for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential is concluded for Reaction product of saturated palm kernel fatty acids and oxybispropanediol.
Executive summary:

No studies are available for Reaction product of saturated palm kernel fatty acids and oxybispropanediol. Data were therefore obtained for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance.

Glycerol, fatty acids, di- and tri-glycerols as well as polyglycerols of fatty acid ester were evaluated as a food additive by EFSA.

Regarding gene mutation in bacteria, studies with bacterial reverse mutation assay (Ames) is described in Salmonella Typhimurium strains TA100, TA1535, TA1537, TA98, TA1538 and Escherichia coli WP2uvrA with data comparable to current standards (OECD Guideline 471). Negative results were obtained in all studies with and without addition of S9 mix.

EFSA (2017d) found no structural alerts for genotoxicity of polyglycerol esters of fatty acids based on their own QSAR analysis for this end-point and present predictions of mutagenicity in silico for oxybispropanediol, capric, lauric, myristic, palmitic and stearic was also negative.

Based on the studies available for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential is concluded for "Reaction product of saturated palm kernel fatty acids and oxybispropanediol".

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the studies available for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, a lack of mutagenic/ genotoxic potential is concluded for Reaction product of saturated palm kernel fatty acids and oxybispropanediol. Thus, "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" should not be classified for mutagenicity.