Coconut oil, reaction products with boric acid (H3BO3), diethanolamine and glycerol

Endpoint summary

Description of key information

A guideline GLP LLNA is available for the registered substance

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 30, 2016 to August 26, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA:J

Sex:

female

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

10, 25, and 50% (w/v)

No. of animals per dose:

5

Positive control results:

Positive control responded as expected

Key result

Parameter:

EC3

Value:

3.9

All animals survived the in-life phase of the study. There were no difficulties in administration of

the test article or with its adherence to the dosed ears. Body weight changes were normal in the QIT. In the

main test, body weight losses were noted but were not significant (<2g). Ear thickness measurements and

individual animal observations indicated that none of the test article treatments resulted in excessive local

dermal irritation.

ID	SI	%B change	%T	B:T change	I-A^kchange	I-A^k:CD69 change
Vehicle	1.0	1.00	70.8	0.99	1.00	1.00
25% HCA (positive control)	5.1	1.52	64.7	1.64	1.51	1.43
0.1% DNCB (positive control)	6.8	1.86	64.9	2.00	1.42	1.20
10% Test Article	4.1	1.11	71.2	1.09	1.27	1.22
25% Test Article	6.7	1.72	65.0	1.84	1.60	1.51
50% Test Article	7.7	1.83	64.9	1.96	1.52	1.31

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Topical application of test article at 10%, 25%, and 50% (w/v) inAOO resulted in SI values greater than 3 (SI > 3). Therefore, this test article is a dermal sensitizer in the LocalLymph Node Assay. Treatment with the test article at 25% and 50% (w/v) resulted in more than a 25% foldincrease compared to the vehicle control for all of the immunophenotyping markers tested. Immunophenotypingresults confirmed that the test article is a dermal sensitizer.

Executive summary:

The substance is classified as a skin sensitizer based on results in a guideline LLNA study. The SI was > 3 at all doses tested (10, 25, 50% (w/v)) and the sensitization response was confirmed with immunophenotyping (positive response at 25 and 50% (w/v)). The EC3 was calculated to be 3.9.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The substance is classified as a skin sensitizer based on results in a guideline LLNA study. The SI was > 3 at all doses tested (10, 25, 50% (w/v)) and the sensitization response was confirmed with immunophenotyping (positive response at 25 and 50% (w/v)). The EC3 was calculated to be 3.9.

The following information is taken into account for any hazard / risk assessment:

Sensitizing based on positive results in LLNA.

Value used for CSA:

 

A.     Qualitative Assessment

The skin sensitization potency based on an EC3 value of 3.9 is considered to be ‘moderate’. Based on ECHA guidance (Chapter R.8 and Part E: Risk Characterization (May, 2016)), moderate skin sensitisers are placed in the moderate hazard band and exposure should be “well-controlled.”

 

B.     Semi-quantitative Assessment

ECHA guidance (Chapter R.8) states that the EC3 value obtained from a LLNA can be used to obtain an induction specific DNEL for sensitization. Based on the formula provided in the ECHA guidance (EC3 X 250 µg/cm² (to convert to dose per skin area) ÷ AF), the following sensitisation DNELs were determined:

 

·        Worker: 97.5 µg/cm²

·        General population: 39 µg/cm²

 

The assessment factors assigned were as follows:

 

·        Interspecies differences: 2.5 (per ECHA guidance)

·        Intraspecies differences: 5 (worker) or 10 (general population) (per ECHA guidance)

 

 

Additional AFs considered per the ECHA guidance and the publication from which it is based on (Api et al., 2008) are:

·        Vehicle effect: 1 – This AF is assigned if the penetration of the substance may be different compared with the LLNA study conducted. This may be influenced by skin irritation potential as well as formulations/vehicles. The notified substance is formulated in a lubricating mineral oil, which is highly viscous and is unlikely to increase the penetration. In addition, the vehicle used in the LLNA was Acetone-olive oil, which is much more likely (compared to lubricating mineral oil) to enhance penetration and the availability of the substance.

·        Use/exposure considerations: 1 – This factor considers how the product is used and is mostly for cosmetic products (Api, et al., 2008); examples included use under occluded conditions. As the notified substance is not intended for exposure and the frequency of exposure is expected to be minimal, no increase in the AF is warranted.

 

The DNEL values obtained for skin sensitization are consistent with values obtained in the literature:

1.      Publication by Schaafsma et al., (2011) proposes the following limits for a moderate skin sensitiser:

·        Worker: 50 µg/cm²/day

·        Consumer: 25 µg/cm²/day

 

2.      Publication by Griem et al., (2003):

·        10-100 µg/cm²for a moderate potency skin sensitizer

 

3.      ECETOC TRA Report No.93 (2004):

·        100 µg/cm²for moderate sensitisers

 

These literature values demonstrate that the DNEL determined based on the LLNA is reasonable. 

References:

1.      ECHA. Guidance on infromation requirements and chemical safety assessment. Chapter R.8: Characterisation of dose concentration-response for human helath. Version 2.1. November, 2012.

2.      ECHA. Guidance on information requirements and chemical safety assessment. Part E: Risk characterisation. Version 3.0. May, 2016.

3.      Api AM, Basketter, DA, Cadby PA, Cano MF, Ellis G, Gerberick GF, Griem P, McNamme PM, Ryan CA, Safford R. Dermal sensitization quantitative risk assessment (QRA) for fragrence ingredients. Regulatory Toxicology and Pharmacology. 2008.

4.      Schaafsma G, Hertsenber, AJ, Marquart J. Risk assessemnt of local dermal effects and skin sensitisation under the EU chemicals regulation REACH: A proposal for qualitative, exposure scenario specific, approah. Regulatory Toxicology and Pharmacology. 2011.

5.      Griem P, Goebel C, Scheffler H. Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data. Regulatory Toxicology and Pharmacology. 2003.

6.      ECETOC. Targeted risk assessment. Technical report No. 93. 2004

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In accordance with criteria for classification as defined in Annex I, Regulation 1272/2008, the test material elicited a response in the Local Lymph Node Assay and is therefore classified as a skin sensitiser, category 1B.