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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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:

Justification for type of information:

PGMS is manufactured by a reaction between stearic acid and propylene glycerol. 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 dermal 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 dermal toxicity must be provided. Limited data on this endpoint is available for Stearic acid, monoester with propane-1,2-diol (PGMS). The possible dermal 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 dermal 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), fatty propylene glycol stearate (PGS) and glycerol stearate (CIR 2015; 2016) as well as data from the latest safety assessment of fatty acids and fatty acids salts as used in cosmetics (CIR 2019).

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.

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:

> 2 000 mg/kg bw

Any other information on results incl. tables

The two main constituents of the UVCB substance are both monoester of propane-diol with octadecanoic acid (45-98%) and the monoester of propane-diol with palmitic acid (2-50%). Thus, the UVCB substance belongs to the group of fatty acid esters and has a very similar structure to the well-known monoglycerides – the only exception being the lack of a OH-group on the C3-carbon in the propylene glycol. The UVCB substance is assessed to be metabolised in the same manner as the monoglycerides via the formation of the fatty acid and the propylene glycol. Detailed study reports on acute dermal toxicity are not available for Stearic acid, monoester with propane-1,2-diol (PGMS), however data on acute oral toxicity of PGMS in expert reviews are available.

In support of a low acute dermal toxicity, data from oral toxicity studies are used. 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 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). PGMS is therefore considered to have low oral toxicity and to be above the doses used for classification.

Supportive of this, low acute oral toxicity of the hydrolysis product PGS was also reported in CIR expert
reviews, with LD50 > 25.8 g/kg bw for PGS (CIR 2015). Further, it is noted that PGS is considered Generally Recognized as Safe (GRAS) for food use (CIR 2015; 2016). No relevant data for acute dermal toxicity data is available for the hydrolysis product propylene glycol as review by CIR (2012).

However, propylene glycol is widely used in cosmetic products due to its properties as an enhancer of
dermal penetration, without any reports of acute dermal toxicity (CIR 2012). Data from acute dermal toxicity studies in rats and rabbits using fatty acids and salts (lithium stearate and stearic acid, respectively) both concluded the acute dermal toxicity to be LD50 > 2000 mg/kg bw.

Based on the studies available for the UVCB substance Stearic acid, monoester with propane-1,2-diol
(PGMS) and the relevant hydrolysis products, it can with a high degree of confidence be concluded that
an assumed acute dermal lethal dose 50 (LD50) for PGMS is above 2000 mg/kg, using a weight of
evidence approach. Thus, PGMS is not to be classified for acute dermal toxicity according to CLP
regulation EC No 1272/2008.

Overall, the available information comprises adequate, reliable studies from reference substances with
similar structure and intrinsic properties. Weight-of-evidence 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.

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 dermal lethal dose 50 (LD50) for PGMS is above 2000 mg/kg. Thus, PGMS is not to be classified for acute dermal toxicity.

Executive summary:

 

Detailed study reports on this endpoint is 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 as well as data on fatty acids and salts (CIR 2019).

 

In support of a low acute dermal toxicity, data from oral toxicity studies are used. 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.

 

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).

No relevant data for acute dermal toxicity data is available for the hydrolysis product propylene glycol as review by CIR (2012). However, propylene glycol is widely used in cosmetic products due to its properties as an enhancer of dermal penetration, without any reports of acute dermal toxicity (CIR 2012).

Data from acute dermal toxicity studies in rats and rabbits using fatty acids and salts (lithium stearate and stearic acid, respectively) both concluded the acute dermal toxicity to be LD50 > 2000 mg/kg bw. In support of a low acute dermal toxicity of fatty acids and salts, a NOAEL > 1000 mg/kg bw/day was set in an OECD 422 study using dermal application og lithium stearate.

 

Overall, it is concluded that based on the oral and dermal toxicity 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 dermal lethal dose 50 (LD50) for PGMS is above 2000 mg/kg. Thus, PGMS is not to be classified for acute dermal toxicity.

 

Overall, it is concluded that based on the oral and dermal toxicity 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 dermal lethal dose 50 (LD50) for PGMS is above 2000 mg/kg. Thus, PGMS is not to be classified for acute dermal toxicity.