Stearic acid, monoester with propane-1,2-diol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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:

PGMS is manufactured by a reaction between stearic acid and propylene glycol. The UVCB substance belongs to the group of fatty acid esters. Within this group is the group of polyglycerol fatty acid esters, which are commonly used in cosmetics and as food ingredients representing substances composed of chemical units of similar structure as the fatty acid esters with propylene glycol. The polyglycerol fatty acids are esters of fatty acids and units of glycerol. The glycerol units represent the propylene glycol in “Stearic acid, monoester with propane-1,2-diol”.

Stearic acid, monoester with propane-1,2-diol (PGMS) is a UVCB substance. The two main constituents of the UVCB substance are the monoester of propane-diol with octadecanoic acid (45-98%) and the monoester of propane-diol with palmitic acid (2-50%). The possible acute oral toxicity of this substance is therefore assessed in the present weight of evidence analysis based on existing data on propane-1,2-diol esters of fatty acids including PGMS (EFSA 2018a) and the relevant hydrolysis products propane-1,2-diol (EFSA 2018b) and fatty propylene glycol stearate (PGS) and glycerol stearate (CIR 2015; 2016).




 

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:

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.

In relation to the data requirements of REACH Annex VIII (10-100 t/y), data on acute oral toxicity must be provided. Limited data on this endpoint is available for Stearic acid, monoester with propane-1,2-diol (PGMS). The possible acute oral toxicity of this UVCB substance is therefore assessed in the present weight of evidence analysis based on existing data on propane-1,2-diol esters as well as the relevant hydrolysis products and the components in the UVCB substance.

Metabolism studies of propane-1,2-diol esters of stearate show that the substances are partially hydrolysed by pancreatic lipase; approx. 70% in 15 h. As the passage through the small intestine has a duration of 6–8 h, unhydrolyzed propane-1,2-diol esters of stearate will be present in the gastrointestinal tract for absorption (EFSA 2018a).

The possible acute oral toxicity of this substance is therefore assessed in the present weight of evidence analysis based on existing data on propane-1,2-diol esters of fatty acids including PGMS (EFSA 2018a) and the relevant hydrolysis products propane-1,2-diol (EFSA 2018b) and fatty propylene glycol stearate (PGS) and glycerol stearate (CIR 2015; 2016).

As the substance is an UVCB-substance and as expert group assessments of the components in the substances are considered the most valid data for the assessment, an overall weight of evidence approach based on these expert evaluations is used for the assessment.

GLP compliance:

not specified

Remarks:

Data extracted from expert opinions

Test material

Test material information

1

Reference substance name:

Stearic acid, monoester with propane-1,2-diol

EC Number:

215-354-3

EC Name:

Stearic acid, monoester with propane-1,2-diol

Cas Number:

1323-39-3

Molecular formula:

C21H42O3

IUPAC Name:

2-hydroxypropyl stearate

Test material form:

solid: pellets

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the studies available for Stearic acid, monoester with propane-1,2-diol (PGMS) and the relevant hydrolysis products and the components of the UVCB substance, it can with a high degree of confidence be concluded that an assumed acute oral lethal dose 50 (LD50) for PGMS is above 10000 mg/kg, and well above 5000 mg/kg which is normally considered as the highest relevant dose level when testing acute toxicity. Thus, PGMS is not to be classified for acute oral toxicity. Overall, available information comprises adequate, reliable studies from
reference substances with similar structure and intrinsic properties. Using data
from comparable substances is justified based on common functional group,
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.

Executive summary:

Detailed study reports on this endpoint are not available for Stearic acid, monoester with propane-1,2-diol (PGMS), however data on PGMS in expert reviews are available. Further, existing data on propylene glycol stearate (PGS) and glyceryl stearate (GS) (CIR 2015; 2016) was used as support in this weight of evidence evaluation.

The LD50 of PGMS from acute oral toxicity studies performed in rats ranges from > 2.7 – 25.8 g/kg bw. In all studies, at ≤ 10 g/kg, no mortality is reported. The only study where mortality was reported, was in the study (number 3 described), where doses up to 32 g/kg was tested. It is also in this study, where the highest LD50-value (25.8 g/kg) was found (EFSA 2018a). The acute oral toxicity of PGMS is therefore considered to have low toxicity and to be above the doses used for classification.

This was also the conclusion form the EFSA evaluation on propane 1,2-diol (EFSA 2018b), stating that overall, the acute toxicity for propanediol-1,2-diol was low. Supportive of this, low acute oral toxicity of the hydrolysis products PGS and GS was also reported in CIR expert reviews, with LD50 > 25.8 g/kg bw for PGS (CIR 2015) and LD50 > 5 g/kg bw for GS (CIR 2016), respectively. Further, it is noted that PGS and GS are considered Generally Recognized as Safe (GRAS) for food use (CIR 2015; 2016).

The overall conclusion is therefore that PGMS has low acute oral toxicity with LD50-values well above the highest dose used for classification as acute toxicity (i.e., 2000- 5000 mg/kg). Hence, low toxicity and no need for classification is concluded for Stearic acid, monoester with propane-1,2-diol (PGMS).

Overall, available information comprises adequate, reliable studies from reference substances with similar structure and intrinsic properties. Using data from comparable substances is justified based on common functional group, 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.