Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key 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 the components in the UVCB substance.

In a two-generation reproduction toxicity study and a prenatal developmental toxicity study in rats with diacylglycerol oil, rich in unsaturated fatty acids (>95%), showed no parental, reproductive and developmental effects up to the highest dose tested (4,630 mg diacylglycerol/kg bw per day). A NOAEL of 4630 mg diacylglycerol/kg bw per day for reproductive and developmental toxicity could be derived.

For glycerol (E 422), several prenatal developmental toxicity studies have been performed with mice, rats and rabbits (EFSA 2017a). NOAEL of 1280,1600 or 1180 mg glycerol/kg bw per day for mice, rats and rabbits, respectively, have been derived.

Based on the studies available for the group of polyglycerol fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, it can with a high degree of confidence be concluded that an assumed NOAEL for "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is far above 1000 mg/kg bw/day which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity. Thus, "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is not to be classified for reproductive or developmental toxicity.

Link to relevant study records

Referenceopen allclose all

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
other: weight of evidence analysis based on expert evaluated data 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:
Data on this endpoint are not available for Reaction product of saturated palm kernel fatty acids and oxybispropanediol. The possible reproductive/developmental toxicity of this substance is therefore assessed in the present weight of evidence analysis based on existing data on the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance. As the target substance and the source substances for the evaluation are UVCB-substances and as expert group assessments of the substances are considered the most valid data for the assessment, an overall weight of evidence approach is used for the assessment. For more details, please see attached weight of evidence document.

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.
Key result
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Sex:
not specified
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
no
Key result
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Sex:
not specified
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
no
Key result
Reproductive effects observed:
no
Conclusions:
Based on the studies available for the group of polyglycerol fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, it can with a high degree of confidence be concluded that an assumed NOAEL for “Reaction product of saturated palm kernel fatty acids and oxybispropanediol” is far above 1000 mg/kg bw/day, which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity. Thus, Reaction product of saturated palm kernel fatty acids and oxybispropanediol is not to be classified for reproductive or developmental toxicity.
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.

In a two-generation reproduction toxicity study and a prenatal developmental toxicity study in rats with diacylglycerol oil, rich in unsaturated fatty acids (>95%), showed no parental, reproductive and developmental effects up to the highest dose tested (4,630 mg diacylglycerol/kg bw per day). A NOAEL of 4630 mg diacylglycerol/kg bw per day for reproductive and developmental toxicity could be derived.

For glycerol (E 422), several prenatal developmental toxicity studies have been performed with mice, rats and rabbits (EFSA 2017a). NOAEL of 1280,1600 or 1180 mg glycerol/kg bw per day for mice, rats and rabbits, respectively, have been derived.

Based on the studies available for the group of polyglycerol fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, it can with a high degree of confidence be concluded that an assumed NOAEL for "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is far above 1000 mg/kg bw/day which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity. Thus, "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is not to be classified for reproductive or developmental toxicity.

Endpoint:
extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
Type of information:
other: weight of evidence analysis based on expert evaluated data 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:
Data on this endpoint are not available for Reaction product of saturated palm kernel fatty acids and oxybispropanediol. The possible reproductive/developmental toxicity of this substance is therefore assessed in the present weight of evidence analysis based on existing data on the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance. As the target substance and the source substances for the evaluation are UVCB-substances and as expert group assessments of the substances are considered the most valid data for the assessment, an overall weight of evidence approach is used for the assessment. For more details, please see attached weight of evidence document.
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.
Justification for study design:
See attached weight of evidence document below
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Sex:
not specified
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
no
Key result
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Sex:
not specified
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
no
Key result
Reproductive effects observed:
no
Conclusions:
Based on the reproductive toxicity studies available for the group of polyglycerol fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, it can with a high degree of confidence be concluded that an assumed NOAEL for “Reaction product of saturated palm kernel fatty acids and oxybispropanediol” is far above 1000 mg/kg bw/day, which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity. Based on the available data on polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance and the absence of adverse effects for reproductive toxicity, the overall weight of evidence point towards no concern for this endpoint. Thus, Reaction product of saturated palm kernel fatty acids and oxybispropanediol is not to be classified for reproductive or developmental toxicity.
Executive summary:

No reproductive toxicity studies (including an EOGRTS study) are available for "Reaction product of saturated palm kernel fatty acids and oxybispropanediol". Reproductive toxicity data were therefore obtained for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance.

In a two-generation reproduction toxicity study and a prenatal developmental toxicity study in rats with diacylglycerol oil, rich in unsaturated fatty acids (>95%), showed no parental, reproductive and developmental effects up to the highest dose tested (4,630 mg diacylglycerol/kg bw per day). A NOAEL of 4630 mg diacylglycerol/kg bw per day for reproductive and developmental toxicity could be derived.

For glycerol (E 422), several prenatal developmental toxicity studies have been performed with mice, rats and rabbits (EFSA 2017a). NOAEL of 1280,1600 or 1180 mg glycerol/kg bw per day for mice, rats and rabbits, respectively, have been derived.

Based on the studies available for the group of polyglycerol fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, it can with a high degree of confidence be concluded that an assumed NOAEL for Reaction product of saturated palm kernel fatty acids and oxybispropanediolis is far above 1000 mg/kg bw/day which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity.

Based on the available data on polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance and the absence of adverse effects for reproductive toxicity, the overall weight of evidence point towards no concern for this endpoint.

Thus, "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is not to be classified for reproductive or developmental toxicity.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available

Effects on developmental toxicity

Description of key 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 the components in the UVCB substance.

In a two-generation reproduction toxicity study and a prenatal developmental toxicity study in rats with diacylglycerol oil, rich in unsaturated fatty acids (>95%), showed no parental, reproductive and developmental effects up to the highest dose tested (4,630 mg diacylglycerol/kg bw per day). A NOAEL of 4630 mg diacylglycerol/kg bw per day for reproductive and developmental toxicity could be derived.

For glycerol (E 422), several prenatal developmental toxicity studies have been performed with mice, rats and rabbits (EFSA 2017a). NOAEL of 1280,1600 or 1180 mg glycerol/kg bw per day for mice, rats and rabbits, respectively, have been derived.

Based on the studies available for the group of polyglycerol fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, it can with a high degree of confidence be concluded that an assumed NOAEL for "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is far above 1000 mg/kg bw/day which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity. Thus, "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is not to be classified for reproductive or developmental toxicity.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
other: weight of evidence analysis based on expert evaluated data 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:
Data on this endpoint are not available for "Reaction product of saturated palm kernel fatty acids and oxybispropanediol". The possible reproductive/developmental toxicity of this substance is therefore assessed in the present weight of evidence analysis based on existing data on the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance. As the target substance and the source substances for the evaluation are UVCB-substances and as expert group assessments of the substances are considered the most valid data for the assessment, an overall weight of evidence approach is used for the assessment. For more details, please see attached weight of evidence document.

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.
Species:
other: weight of evidence analysis based on expert evaluated data on hydrolysis products and structural analogues using data from different species.
Remarks on result:
other: Based on the studies available for the group of polyglycerol fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, it is concluded that an assumed NOAEL is far above 1000 mg/kg bw/day.
Remarks on result:
other: Based on the studies available for the group of polyglycerol fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, it is concluded that an assumed NOAEL is far above 1000 mg/kg bw/day.
Key result
Developmental effects observed:
no
Lowest effective dose / conc.:
1 000 mg/kg bw/day (actual dose received)
Treatment related:
no
Conclusions:
Based on the studies available for the group of polyglycerol fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, it can with a high degree of confidence be concluded that an assumed NOAEL for “Reaction product of saturated palm kernel fatty acids and oxybispropanediol” is far above 1000 mg/kg bw/day, which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity. Thus, Reaction product of saturated palm kernel fatty acids and oxybispropanediol is not to be classified for reproductive or developmental toxicity.
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.

In a two-generation reproduction toxicity study and a prenatal developmental toxicity study in rats with diacylglycerol oil, rich in unsaturated fatty acids (>95%), showed no parental, reproductive and developmental effects up to the highest dose tested (4,630 mg diacylglycerol/kg bw per day). A NOAEL of 4630 mg diacylglycerol/kg bw per day for reproductive and developmental toxicity could be derived.

For glycerol (E 422), several prenatal developmental toxicity studies have been performed with mice, rats and rabbits (EFSA 2017a). NOAEL of 1280,1600 or 1180 mg glycerol/kg bw per day for mice, rats and rabbits, respectively, have been derived.

Based on the studies available for the group of polyglycerol fatty acid esters, the relevant hydrolysis products and the components of the UVCB substance, it can with a high degree of confidence be concluded that an assumed NOAEL for "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is far above 1000 mg/kg bw/day which is normally considered as the highest relevant dose level when testing for reproduction and prenatal developmental toxicity. Thus, "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is not to be classified for reproductive or developmental toxicity.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on weight of evidence it can be concluded that "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is not to be classified for reproductive toxicity.