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Diss Factsheets

Administrative data

Description of key information

The weight of evidence is that the substance is not a dermal sensitiser, despite some conflicting data.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
Between 1994 and1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
guinea pig maximization test
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Conducted prior to 1999
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
50% Freund's Complete Adjuvant (FCA)
Day(s)/duration:
Day 1
Adequacy of induction:
not specified
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
2.5% hydroxystearic acid (HSA) in corn oil on day 1; on day 8, 10% HSA in corn oil
Day(s)/duration:
Days 1 and 8
Adequacy of induction:
not specified
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
2.5% HCA in 50% FCA/0.9% saline (50/50 test group) OR 50% corn oil in FCA/0.9% saline (50/50 control group)
Day(s)/duration:
Day 1
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
10% Sodium lauryl sulfate (SDS)
Day(s)/duration:
Day 7
Adequacy of induction:
not specified
No. of animals per dose:
10 males, 10 females
Details on study design:
Intradermal and epicutaneous exposure.
The intradermal injections were administered (interscapular) on day 1 to five groups of animals: 50% Freund’s complete adjuvant (FCA) in 0.9% saline; 2.5% hydroxystearic acid in corn oil or vehicle alone; or 2.5% hydroxystearic acid in FCA/0.9% saline (50/50, v/v; test group); and the test material in FCA/0.9% saline or vehicle control (corn oil) in FCA.

One week after the initial intradermal injections, 10% sodium lauryl sulfate (SLS), 0.5 ml, was applied to the induction site. The next day (day 8), occlusive patches with the dermal dose (10% 12-HSA in corn oil) were applied to the test animals for 48 h; controls received patches with vehicle only. A rest period of 14 days occurred. On day 22, all animals received a 24-h occlusive challenge patch (2.5% hydroxystearic acid in corn oil). Control patches were placed on the left flank, and test material patches on the right flank. Sites were evaluated after 24, 48 and 72 h.
Challenge controls:
vehicle (corn oil)
Positive control substance(s):
not specified
Positive control results:
Positive findings in both vehicle control (corn oil) animals and in test material animals in experiment 1. Results of the second experiment are summarized below.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
discrete erythma
Remarks on result:
other: indication of irritation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5% in corn oil
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
discrete erythema
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
7
Total no. in group:
20
Clinical observations:
discrete erythema
Remarks on result:
other: indication of irritation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5% in corn oil
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
discrete erythema
Remarks on result:
not determinable because of methodological limitations
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
discrete erythema
Remarks on result:
other: suggestion of irritation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5% in corn oil
No. with + reactions:
9
Total no. in group:
10
Clinical observations:
discrete erythema
Remarks on result:
not determinable because of methodological limitations
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
discrete erythema
Remarks on result:
other: indication of irritation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5% in corn oil
No. with + reactions:
6
Total no. in group:
20
Clinical observations:
discrete eythema
Remarks on result:
not determinable because of methodological limitations
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
other:
Dose level:
All doses
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
2
Total no. in group:
10
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
1 or 5% in acetone
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
1 or 5% in acetone
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

The first test used challenge doses too high, resulting in erythema in both controls and test animals.

The second test used lower patch challenge doses, these were difficult to interpret due to positive findings in the corn oil control animals. After the second challenge with the alternate vehicle (acetone), no cutaneous reactions were noted at any sites at the 24 h time point. At the 48 h time point, discrete erythema was reported at the vehicle patch site of 2 of 10 vehicle controls, and at 2/10 animals patched with the test material. There was no increase in the occurrence of positives between the control and test patches.

Interpretation of results:
GHS criteria not met
Conclusions:
In a guinea pig maximization test using 2.5% (intradermal) and 10% (epicutaneous) 12-hydroxystearic acid as induction dose and either 2.5%, 1.0% or 0.5% as elicitation dose, the substance did not result in an increase in the number of animals showing erythema, compared to corn oil or acetone vehicle controls. 12-Hydroxysteaic acid was evaluated as not inducing delayed contact hypersensitivity reactions, under the conditions of this study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

While there is no known data specifically on the sensitisation potential of glyceryl monohydroxystearate (GMHS), there is a large body of knowledge of structurally related ricinoleates, stearates and castor oil derivatives. Another analogue, 12 -HSA, was tested in two types of studies as reviewed by the U.S. CIR Expert Panel: a LLNA (found to be positive) and two guinea pig maximisation tests, which were negative. The acid functional group may have impacted the outcome of the sensitisation studies; 12 -HSA is known to be irritating, and acids can result in the breaching of the skin barrier. Furthermore, glyceryl monoesters can be dermal penetration enhancers, allowing other concurrently applied materials or impurities to preferentially enter the dermal tissue (CIR, 2015). Preclinical studies (animal) and clinical studies (human volunteers) on a large category of glycerides (Monoglyceryl Monoesters, including Glyceryl Hydroxystearate (CIR, 2015) were the basis on which the Expert Panel concluded that category members were safe for use in cosmetics. Some of the positive animal outcomes reviewed in the CIR assessment may be explained by the presence of rosin derivatives or an unsaturated fatty acid functional group, which has been noted to cause potential "false positive" results in the LLNA assay, compared with outcomes in guinea pig assays (Kreiling et al., Food Chem Toxicol 46:1896 -1904, 2008, and Yamashita K et al., J. Toxicol Sciences 40(6):843 -853, 2015). Monoglycerides including glyceryl stearate, and triglycerides such as castor oil, were reviewed as part of a large category of Glycerides, (OECD HPV Programme, 2014), and the SIAR panel concluded that the untested members of the category were not expected to not be sensitisers. While there are a few case reports in humans of allergic response to castor oil derivatives, the Expert committee of the CIR, concerned with intentional dermal exposure to castor oil derivatives, concluded that the substances are safe for use in cosmetic products.

The weight of evidence is that glyceryl monohydroxystearate is not a dermal sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

There are no known experimental or clinical data on the dermal sensitisation of glyceryl monohydroxystearate. Therefore, an analogue approach is used to evaluate this hazard for this endpoint, using 12 -hydroxystearic acid (12 -HSA), hydrogenated castor oil and castor oil, each of which possess additional functional groups not found in the registered substance and therefore represent worst case scenarios. Two of three of these compounds have relevant experimental or clinical data which shows them to be non-sensitisers, while 12 -HSA also has a positive LLNA. The acid functional group, known to break down the skin barrier, can help explain the LLNA findings. The castor oils have an unsaturated bond in the alkyl chain, and testing on these compounds may lead to "false positives" in the LLNA. Therefore, larger categories of glycerides (CIR 2015 and OECD 2014) can be consulted, where the findings of sensitisation studies result in the conclusion that long chain fatty glycerides are not dermal sensitisers. The long history of safe use of castor oil and hydrogenated castor oil in cosmetic products suggests that glyceryl monohydroxystearic is not a sensitiser. There is insufficient experimental data to meet the classification criteria for sensitisation according to Regulation EC No. 1272/2008. The substance is not classified.