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Administrative data

Description of key information

No repeated dose toxicity 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.

In humans, 19-24 years of age, exposed for 3 weeks to polyglycerol esters of fatty acids though the diet, no signs of toxicity were seen (EFSA, 2017d).

In the available rat studies, animals were exposed to polyglycerol esters of fatty acids for 90 days (10% polyglycerol ester per day) and 22 weeks (9% polyglycerol ester per day) (EFSA, 2017d). No toxicity was seen in any of the studies using 10 % polyglycerol ester (equivalent to 9000 mg/kg bw/d) and 9% (7290 mg/kg bw/d), respectively.

Data from 90-day and chronic toxicity studies in rats with di- and triglycerides, identified NOAELs at 3178- and 1946 mg/kg bw/day, respectively. In both studies, test substance was given through the diet, using dose levels up to the NOAEL values identified (Morita et al. (2008a) and Chengelis et al., 2006b, both identified in EFSA (2017c)).

No adverse effects were found from exposure to medium-chain triglycerides based on decanoic acid and octanoic acid. The NOAEL based on these studies was ≥ 7000 mg/kg bw/day (CLH report octanoic acid, 2012). For medium and long chain triglycerides, the NOAEL is reported to be ≥ 8000 mg/kg bw/day (Zhou et al., 2017).

For the fatty acids, a NOAEL for decanoic acid is reported to be > 1000 mg/kg bw/day (CAR Capric acid, 2013). One study was performed on tetra decanoic acid (Lauric acid) in rats reporting a NOEL of > 6000 mg/kg/day (Burdock et al., 2007). Further data from repeated dose toxicity studies in rats (subchronic, 18-24 weeks) using saturated fatty acids (C12-C18), identified a NOAEL ≥ 9000 mg/kg bw/day (10% in diet), which was the highest dose level tested (EFSA (2017b)).

Studies on repeated dose toxicity on synthetic and natural glycerine fed orally to rats is reported with a NOAEL of 10 000 mg/kg bw/d (ECHA, 2017a) indicating that the glycerols are non-toxic.

Based on the available studies on the group of polyglyceryl fatty acid esters and the relevant hydrolysis products described above, it can from an overall weight of evidence approach be concluded that the UVCB substance “Reaction product of saturated palm kernel fatty acids and oxybispropanediol” is of very low concern for repeated dose toxicity. 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 repeated dose toxicity. Thus, no STOT RE classification should apply for the substance.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
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 order to assess the repeated dose toxicity of the substance, the toxicity of polyglyceryl fatty acid esters in general is therefore considered. As polyglycerol contains of diglycerols together with triglycerols and tetraglycerols, and as information on metabolism in vivo and in vitro is available, read-across to data on these substances is considered acceptable for the present substance.

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 results are based on a weight of evidence analysis from collection of studies extracted from the literature. For more details please refer to the attached weight of evidence document.

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 order to assess the repeated dose toxicity of the substance, the toxicity of polyglyceryl fatty acid esters in general is therefore considered.

As polyglycerol contains of diglycerols together with triglycerols and tetraglycerols, and as information on metabolism in vivo and in vitro is available, read-across to data on these substances is considered acceptable for the present substance. In general, data on polyglycerol esters of fatty acids, mono- and diglycerides of fatty acids, glycerol/diglycerol and fatty acids will be used.


Key result
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Basis for effect level:
other: Collection of relevant data. Please see attached document
Critical effects observed:
no
Conclusions:
Based on the available studies on the group of polyglyceryl fatty acid esters and the relevant hydrolysis products described above, it can based on an overall weight of evidence approach be concluded that the compound Reaction product of saturated palm kernel fatty acids and oxybispropanediol is of very low concern for repeated dose toxicity. Thus, no STOT RE classification should apply for the substance.
Executive summary:

No repeated dose toxicity 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.

In humans, 19-24 years of age, exposed for 3 weeks to polyglycerol esters of fatty acids though the diet, no signs of toxicity were seen (EFSA, 2017d).

In the available rat studies, animals were exposed to polyglycerol esters of fatty acids for 90 days (10% polyglycerol ester per day) and 22 weeks (9% polyglycerol ester per day) (EFSA, 2017d). No toxicity was seen in any of the studies using 10 % polyglycerol ester (equivalent to 9000 mg/kg bw/d) and 9% (7290 mg/kg bw/d), respectively.

Data from 90-day and chronic toxicity studies in rats with di- and triglycerides, identified NOAELs at 3178- and 1946 mg/kg bw/day, respectively. In both studies, test substance was given through the diet, using dose levels up to the NOAEL values identified (Morita et al. (2008a) and Chengelis et al., 2006b, both identified in EFSA (2017c)).

No adverse effects were found from exposure to medium-chain triglycerides based on decanoic acid and octanoic acid. The NOAEL based on these studies was ≥ 7000 mg/kg bw/day (CLH report octanoic acid, 2012). For medium and long chain triglycerides, the NOAEL is reported to be ≥ 8000 mg/kg bw/day (Zhou et al., 2017).

For the fatty acids, a NOAEL for decanoic acid is reported to be > 1000 mg/kg bw/day (CAR Capric acid, 2013). One study was performed on tetra decanoic acid (Lauric acid) in rats reporting a NOEL of > 6000 mg/kg/day (Burdock et al., 2007). Further data from repeated dose toxicity studies in rats (subchronic, 18-24 weeks) using saturated fatty acids (C12-C18), identified a NOAEL ≥ 9000 mg/kg bw/day (10% in diet), which was the highest dose level tested (EFSA (2017b)).

Studies on repeated dose toxicity on synthetic and natural glycerine fed orally to rats is reported with a NOAEL of 10 000 mg/kg bw/d (ECHA, 2017a) indicating that the glycerols are non-toxic.

Based on the available studies on the group of polyglyceryl fatty acid esters and the relevant hydrolysis products described above, it can from an overall weight of evidence approach be concluded that the UVCB substance Reaction product of saturated palm kernel fatty acids and oxybispropanediol is of very low concern for repeated dose toxicity. 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 repeated dose toxicity. Thus, no STOT RE classification should apply for the substance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the available studies on the group of polyglyceryl fatty acid esters and the relevant hydrolysis products described above, it can based on an overall weight of evidence approach be concluded that the compound "Reaction product of saturated palm kernel fatty acids and oxybispropanediol" is of very low concern for repeated dose toxicity. Thus, no STOT RE classification should apply for the substance.