Docosanoic acid, monoester with glycerol

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Type of information:

other: weight of evidence

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

Because of the structural and functional similarities, data from other glyceryl monoesters are included in this weight of evidence assessment as supporting data.

The following expert opinion (attached in section 13) will be used in the weight of evidence approach:

CIR 2016: Cosmetic Ingredient Review. Safety assessment of monoglyceryl monoesters as used in cosmetics. Final amended report, January 15, 2016.

CIR 2019: Safety Assessment of Fatty Acids & Fatty Acid Salts as Used in Cosmetics

EFSA 2017: Re-evaluation of glycerol (E 422) as a food additive

OECD SIDS 2001: Docosanoic acid. CAS No: 112-85-6. SIDS Initial Assessment Report for 13th SIAM

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Principles of method if other than guideline:

In a 28 day repeated dose toxicity study glyceryl rosinate was administered via the diet at 30% in 70% corn oil, given at 0.2% and 1.0%. No effects on mortality morbidity, clinical signs, food consumption, or body weight gain; no gross or microscopic lesions were observed. The NOAEL was set at 1%.

In 28 days gavage study 10 male and 5 female Wistar rats (recovery group with an additional 5 males and females in the control and high dose group), glycerides, C8-18 and C18-unsatd mono- and di-, acetates was administered at 0, 100, 300 and 1000 mg/kg/day. No clinical signs of toxicity: no toxicological relevant changes in haematology, clinical chemistry, organ weights or gross or microscopic lesions. The NOAEL was set at 1000 mg/kg bw/day.

In an oral (gavage) OECD 422 study evaluating repeated dose toxicity as well as screening for reproduction and developmental toxicity, Docosanoic acid (behenic acid) did not shown any repeated dose toxicity. 13 male and 13 female Sprague-Dawley rats per dose group was given 0, 100, 300, or 1000 mg/kg bw/day in corn oil. Males were treated 42 days and females were treated for 14 days prior to mating to day 3 of lactation. The NOAEL was set to be > 1000 mg/kg bw/day as no treatment-related adverse effects were observed.

In support of the above conclusion, CIR concluded no concern for repeated dose toxicity in their evaluation of fatty of monoglyceryl monoesters (2016). The same CIR conclusion was drawn in relation to fatty acids and fatty acids salts (2019) where the NOAELs for Behenic Acid (up to 1000 mg/kg bw/day), Calcium Stearate (up to 2000 mg/kg bw/day), and Capric Acid (up to 1000 mg/kg bw/day) were greater than or equal to the highest doses tested in oral studies.

In their evaluation of glycerol, EFSA (2017) also concluded no concern for repeated dose toxicity. Overall conclusion was no safety concern regarding the use of glycerol (E 422) as a food additive.

GLP compliance:

not specified

Remarks:

Data from expert opinions

Test material

Test material information

Constituent 1

Reference substance name:

Docosanoic acid, monoester with glycerol

EC Number:

250-097-0

EC Name:

Docosanoic acid, monoester with glycerol

Cas Number:

30233-64-8

Molecular formula:

C25H50O4

IUPAC Name:

2-hydroxy-1-(hydroxymethyl)ethyl docosanoate

Test material form:

solid

Results and discussion

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Remarks on result:

other: Collection of relevant data, see attached file

Target system / organ toxicity

Key result

Critical effects observed:

no

Lowest effective dose / conc.:

1 000 mg/kg bw (total dose)

Applicant's summary and conclusion

Conclusions:

Based on the available data used in a weight of evidence approach, it can be
concluded that glycerol monobehenate is of very low concern for repeated dose toxicity;
and it can with a high degree of confidence be concluded that an assumed NOAEL
is 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 according to (EC) No 1272/2008 is not warranted.

Executive summary:

Docosanoic acid, monoester with glycerol (glycerol monobehenate) is a mono constituent substance with a purity of 80-90%. Data on repeated dose toxicity of glycerol monobehenate was not available.
However, data from other glyceryl monoesters with structural and functional similarities are available and were included in this weight of evidence assessment. Data on Docosanoic acid (behenic acid) was also used as well as data on glycerol. No signs of toxicity were observed in two 28-day studies for glyceryl rosinate and glycerides, C8-18 and C18-unsatd. mono- and di-, acetates. The NOAEL for these two studies is therefore the highest dose tested which was 1000 mg/kg bw/day. This was also concluded for Docosanoic acid (behenic acid) in an OECD 422 study, the NOAEL was set to be > 1000 mg/kg bw/day as no treatment-related adverse effects were observed. For glycerol, EFSA also concluded no concern for repeated dose toxicity (EFSA, 2017) in their evaluation of glycerol. Overall, they concluded that there was no safety concern regarding the use of glycerol (E 422) as a food additive. Based on the available data used in a weight of evidence approach, it can be concluded that monobehenate is of very low concern for repeated dose toxicity; and it can with a high degree of confidence be concluded that an assumed NOAEL is 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 according to (EC) No 1272/2008 is not warranted.
The available information comprises adequate, reliable studies from reference substances with similar structure and intrinsic properties. The weight-of-evidence approach is justified based on common functional group and common
precursors/breakdown products. The information from these independent sources is consistent and provides sufficient weight of evidence leading to an endpoint
conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006.