Registration Dossier

No studies are available for Stearic acid, monoester with propane-1,2-diol (PGMS). Data were therefore obtained for the group of propylene glycol stearate (PGS), the relevant hydrolysis products and structural analogues. PGMS and PGS are both UVCB substances, formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid) but PGS has a higher diester content and lower monoester content than PGMS. The UVCB substance belongs to the group of PGS, which are commonly used in cosmetics and as food ingredients (CIR 1983 and CIR 2015).

In order to assess the skin and eye irritation potential of PGMS, the toxicity of PGS in general is therefore considered. Based on the data on PGS, the close similarity between PGS and PGMS and the identical QSAR predictions for the skin irritation potential of PGS and PGMS it can by weight of evidence be concluded that the data is considered acceptable for the present substance.

Three experimental animal dermal irritation tests are available on propylene glycol stearate (PGS). This testing indicates no or very mild skin irritation potential of the substance. Further, a clinical evaluation with patch testing of 80 human subjects indicate lack of dermal irritation. PGS is very comparable to Stearic acid, monoester with propane-1,2-diol (PGMS) as the substances are formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid) but PGS has a higher diester content and lower monoester content than PGMS. Based on the data on PGS, the close similarity between PGS and PGMS and further based on identical QSAR predictions for the skin irritation potential of the two substances, it can by weight of evidence be concluded that PGMS is not a skin irritant.

Three experimental animal eye irritation tests are available on propylene glycol stearate (PGS). This testing indicates no or very mild eye irritation potential of the substance. PGS is very comparable to Stearic acid, monoester with propane-1,2-diol (PGMS) as the substances are formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid) although PGS has a higher diester content and lower monoester content than PGMS. Based on the data on PGS, the close similarity between PGS and PGMS and further based on identical QSAR predictions for the eye irritation potential of the two substances, it can by weight of evidence be concluded that PGMS is not an eye irritant.

Overall, PGMS should not according to the CLP criteria, EC no 1272/2008 be classified with respect to skin and eye irritation.

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.

Reference

Endpoint:

skin irritation: in vivo

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:

No studies are available for Stearic acid, monoester with propane-1,2-diol (PGMS). Data were therefore obtained for the group of propylene glycol stearate (PGS), the relevant hydrolysis products and structural analogues.
PGMS and PGS are both UVCB substances, formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid) but PGS has a higher diester content and lower monoester content than PGMS. The UVCB substance belongs to the group of PGS, which are commonly used in cosmetics and as food ingredients (CIR 1983 and CIR 2015).

In order to assess the skin irritation potential of PGMS, the toxicity of PGS in general is therefore considered. Based on the data on PGS, the close similarity between PGS and PGMS and the identical QSAR predictions for the skin irritation potential of PGS and PGMS it can by weight of evidence be concluded that the data is considered acceptable for the present substance.

In general, data from the following expert assessments evaluating PGS are used in a weight of evidence approach:
CIR (1983). Final report on the safety assessment of propylene glycol stearate and propylene glycol stearate self-emulsifying. J Am Coll Toxicol 2(5), 101-124.
CIR (2015). Safety Assessment of Propylene Glycol Esters as Used in Cosmetics. Final amended report December8-9, 2014. 23 pp.

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.

Stearic acid, monoester with propane-1,2-diol (PGMS) is an UVCB substance, formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid). The UVCB substance belongs to the group of propylene glycol stearate (PGS), which are commonly used in cosmetics and as food ingredients.

In order to assess the skin irritation potential, the toxicity of PGS in general is therefore considered. PGS is very comparable to PGMS as the substances are formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid) although PGS has a higher diester content and lower monoester content than PGMS. As expert-reviewed information/reports on in vivo metabolism and toxicity is available, read-across to data on PGS is considered acceptable for the present substance.

Remarks on result:

other: Based on the data on PGS, the close similarity between PGS and PGMS and the identical QSAR predictions for skin and eye irritation potential of the two substances, it can by weight of evidence be concluded that PGMS is not a skin and eye irritant.

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.

Three experimental animal dermal irritation tests are available on propylene glycol stearate (PGS). This testing indicates no or very mild skin irritation potential of the substance. Further, a clinical evaluation with patch testing of 80 human subjects indicates lack of dermal irritation. PGS is very comparable to Stearic acid, monoester with propane-1,2-diol (PGMS) as the substances are formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid) but PGS has a higher diester content and a lower monoester content than PGMS. Based on the data on PGS, the close similarity between PGS and PGMS and further based on identical QSAR predictions for the skin irritation potential of the two substances, so it can by weight of evidence be concluded that PGMS is not a skin irritant.

Thus, according to the CLP criteria, EC no 1272/2008, PGMS should not be classified with respect to
skin irritation.

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.

Interpretation of results:

GHS criteria not met

Conclusions:

No studies are available for Stearic acid, monoester with propane-1,2-diol (PGMS). Data on skin irritation were therefore obtained for the group of propylene glycol stearate (PGS) in the UVCB substance (CIR 1983 and CIR 2015). Results from the human and animal studies on skin irritation of PGS were mostly negative results on skin irritation. Therefore, it is considered most likely that the same will apply for PGMS. Based on an overall weight of evidence from the available data it is concluded that PGMS is not to be classified for skin irritation, as the CLP criteria for classification, EC no 1272/2008 is not fulfilled.

Executive summary:

No studies evaluating skin irritation are available for the UVCB substance stearic acid, monoester with propane-1,2-diol (PGMS) but data on propylene glycol stearate (PGS) is available from CIR safety assessments reports evaluating the use of PGS in cosmetics (CIR 1983 and CIR 2015).

Three experimental animal dermal irritation tests are available on PGS. This testing indicates no or very mild skin irritation potential of the substance. Further, a clinical evaluation with patch testing of 80 human subjects indicate lack of dermal irritation. PGS is very comparable to PGMS as the substances are formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid) but PGS has a higher diester content and lower monoester content than PGMS. Based on the data on PGS, the close similarity between PGS and PGMS and further based on identical QSAR predictions for the skin irritation potential of the two substances, it can by weight of evidence be concluded that PGMS is not a skin irritant and is not to be classified for skin irritation, as the CLP criteria for classification, EC no 1272/2008 is not fulfilled.

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.

Endpoint conclusion:

no adverse effect observed (not irritating)

Reference

Endpoint:

eye irritation: in vivo

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:

No studies are available for Stearic acid, monoester with propane-1,2-diol (PGMS). Data were therefore obtained for the group of propylene glycol stearate (PGS), the relevant hydrolysis products and structural analogues.
PGMS and PGS are both UVCB substances, formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid) but PGS has a higher diester content and lower monoester content than PGMS. The UVCB substance belongs to the group of PGS, which are commonly used in cosmetics and as food ingredients (CIR 1983 and CIR 2015).

In order to assess the eye irritation potential of PGMS, the toxicity of PGS in general is therefore considered. Based on the data on PGS, the close similarity between PGS and PGMS and the identical QSAR predictions for the eye irritation potential of PGS and PGMS it can by weight of evidence be concluded that the data is considered acceptable for the present substance.

In general, data from the following expert assessments evaluating PGS are used in a weight of evidence approach:
CIR (1983). Final report on the safety assessment of propylene glycol stearate and propylene glycol stearate self-emulsifying. J Am Coll Toxicol 2(5), 101-124.
CIR (2015). Safety Assessment of Propylene Glycol Esters as Used in Cosmetics. Final amended report December8-9, 2014. 23 pp.

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.

Stearic acid, monoester with propane-1,2-diol (PGMS) is an UVCB substance, formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid). The UVCB substance belongs to the group of propylene glycol stearate (PGS), which are commonly used in cosmetics and as food ingredients.

In order to assess the eye irritation potential, the toxicity of PGS in general is therefore considered. PGS is very comparable to PGMS as the substances are formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid) although PGS has a higher diester content and lower monoester content than PGMS. As expert-reviewed information/reports on in vivo metabolism and toxicity are available, read-across to data on PGS is considered acceptable for the present substance.

Remarks on result:

other: Based on the studies available for propylene glycol stearate, the relevant hydrolysis products and the components of the UVCB substance, it is concluded that the test substance is not an eye irritant

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.

Three experimental animal eye irritation tests are available on propylene glycol stearate (PGS). This testing indicates no or very mild eye irritation potential of the substance. Based on the data on PGS, the close similarity between PGS and PGMS and further based on identical QSAR predictions for the eye irritation potential of the two substances, it can by weight of evidence be concluded that PGMS is not an
eye irritant.

Thus, according to the CLP criteria, EC no 1272/2008, PGMS should not be classified with respect to eye irritation.

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.

Interpretation of results:

GHS criteria not met

Conclusions:

No studies are available for Stearic acid, monoester with propane-1,2-diol (PGMS). Data on eye irritation were therefore obtained for the group of propylene glycol stearate (PGS) in the UVCB substance (CIR 1983 and CIR 2015). Results from the three animal studies on eye irritation of PGS were mostly negative results. Therefore, it was concluded that PGS is not an eye irritant. Based on an overall weight of evidence, PGMS should not according to the CLP criteria, EC no 1272/2008 be classified with respect to eye irritation.

Executive summary:

No studies are available for Stearic acid, monoester with propane-1,2-diol (PGMS). Data on eye irritation were therefore obtained for the group of propylene glycol stearate (PGS) in the UVCB substance (CIR 1983 and CIR 2015).

Three experimental animal eye irritation tests are available on propylene glycol stearate (PGS). This testing indicates no or very mild eye irritation potential of the substance. PGS is very comparable to Stearic acid, monoester with propane-1,2-diol (PGMS) as the substances are formed by esterification of propane-1,2-diol and stearic acid (and to a lesser extent palmitic acid) although PGS has a higher diester content and lower monoester content than PGMS. Based on the data on PGS, the close similarity between PGS and PGMS and further based on identical QSAR predictions for the eye irritation potential of the two substances, it can by weight of evidence be concluded that PGMS is not an eye irritant.

Thus, PGMS should not according to the CLP criteria, EC no 1272/2008 be classified with respect to eye irritation.

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.

Endpoint conclusion:

no adverse effect observed (not irritating)

Endpoint conclusion:

no study available

Based on an overall weight of evidence from the available data on the group of propylene glycol stearate (PGS), it is concluded that Stearic acid, monoester with propane-1,2-diol (PGMS) is not to be classified for skin- and eye irritation, as the CLP criteria for classification is not fulfilled. In support, CIR (1983) and CIR (2015) concluded that propylene glycol stearate (PGS) is safe for use in cosmetics.