Reaction mass of bis(2-methylpropyl) (1R,2R,3R,6S)-3,6-dimethylcyclohexane-1,2-dicarboxylate and bis(2-methylpropyl) (1S,2S,3R,6S)-3,6-dimethylcyclohexane-1,2-dicarboxylate

Endpoint summary

Description of key information

Skin sensitisation, In-Vivo (LLNA) - Not sensitising

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:

30 Aug - 19 Sep, 2017

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: H1L002
- Expiration date of the lot/batch: 31 Dec 2017
- Purity test date: 99.0%

Species:

mouse

Strain:

CBA

Remarks:

CaOlaHsd

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 9 – 13 weeks (Pre-tests 11-13 weeks; Main test 1-10 weeks)
- Weight at study initiation: Pre tests: 19.1 – 22.5g; Main test: 17.6 - 23.0 g
- Housing: Makrolon Type II (pre-test) / III (main study), with wire mesh top, granulated soft wood bedding.
- Diet: 2018C Teklad Global 18% protein rodent diet (certified), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 45-65%
- Photoperiod: artificial light: 6.00 a.m. - 6.00 p.m

Vehicle:

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

Concentration:

2.5%, 5%, 10 %

No. of animals per dose:

4

Details on study design:

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node Assay
- Criteria used to consider a positive response: A test item is regarded as a sensitiser in the LLNA if the exposure to one or more test concentration resulted in a 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.).
In this study Stimulation Indices of 0.43, 0.73, and 1.09 were determined with the test item at concentrations of 2.5, 5, and 10% in acetone/olive oil (4+1 v/v). The EC3 value could not be calculated, since none of the tested concentrations induced a S.I. greater than the threshold value of 3.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Key result

Parameter:

EC3

Remarks on result:

not determinable

Parameter:

SI

Value:

0.43

Test group / Remarks:

2.5% (v/v)

Parameter:

SI

Value:

0.73

Test group / Remarks:

5% (v/v)

Parameter:

SI

Value:

1.09

Test group / Remarks:

10% (v/v)

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was not a skin sensitiser under the test conditions of the study.

The animals did not show any signs of systemic toxicity during the course of the study and no cases of mortality were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Justification for classification or non-classification

An in-vivo skin sensitisation study (local lymph node assay) was conducted (Envigo study WV64GB, 2017) to assess the potential of SIBE138 to cause skin sensitisation. SIBE138 was applied to skin at concentrations which were achieveable while not inducing systemic toxicity or excessive local skin irritation. Recorded stimulation indices were less than 3 at all concentrations tested; on this basis it was concluded that SIBE138 was not found to be a skin sensitiser under the test conditions employed.

On the basis that SIBE138 was found not to be sensitising in a relevant in-vivo test, the substance will not be classifed for skin sensitisation according to the CLP regulation (Regulation (EC) 1272/2008).

No relevant human or animal data are available to permit an independent assessment of the potential for respiratory sensitisation.