Registration Dossier

Administrative data

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 Polyglycerol-2-caprate. 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.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

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.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

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

Target system / organ toxicity (P0)

Critical effects observed:
no

Results: F1 generation

Effect levels (F1)

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

Target system / organ toxicity (F1)

Critical effects observed:
no

Overall reproductive toxicity

Key result
Reproductive effects observed:
no

Applicant's summary and conclusion

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 polyglycerol-2-caprate 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, Polyglycerol-2-caprate is not to be classified for reproductive or developmental toxicity.
Executive summary:

No studies are available for polyglycerol-2-caprate. Data were therefore obtained for the group of polyglyceryl fatty acid esters, the relevant hydrolysis products and the components in the UVCB substance.

One long term study on polyglycerol esters in rats is described. Twenty-two rats were fed a diet containing 1.5% polyglycerol esters for 3 generations. No significant variation were found on fertility and reproductive performance. Gross and histological examination of the third generation revealed no consistent abnormalities related to the test substance (JECFA 1967).

Further, one study on feeding of medium-chain triglycerides containing 35% Decanoic acid and 51% Octanoic acid exists. The study was conducted for 47 weeks in male and female rat, with exposure from 3 weeks before mating and on. The NOAEL was determined to be ≥ 8000 mg/kg bw/day (CLH report octanoic acid 2012). Similarly, no effect were found in a developmental study in SD rats exposed to a triacylglycerols mixture containing 30% (w/w) C8 and C10 fatty acids (Zhou et al. 2017).

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 polyglycerol-2-caprate 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, polyglycerol-2-caprate is not to be classified for reproductive or developmental toxicity.