Dichlorotricyclo[8.2.2.24,7]hexadeca-1(12),4,6,10,13,15-hexaene, mixed isomers

Endpoint summary

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:

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)

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA:J

Remarks:

CrHsd

Sex:

female

Vehicle:

methyl ethyl ketone

Concentration:

In the preliminary assay, dose concentrations of 1%, 2.5%, 5.0% and 10% (w/v) in methyl ethyl ketone (MEK) revealed no erythema and ear thickness increases was less than 25%. Therefore, dose concentrations of 1%, 5% and 10% (w/v) in methyl ethyl ketone (MEK) DPX-C (Di-Cloro-Di-p-Xililene) were evaluated in the main study.

No. of animals per dose:

8 (2 mice/group) for preliminary assay, and 25 (5 mice/group) for main study.

Details on study design:

Females (nulliparous and non-pregnant).

Positive control substance(s):

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

Parameter:

SI

Value:

1.63

Test group / Remarks:

1% MEK

Parameter:

SI

Value:

2.51

Test group / Remarks:

5% MEK

Parameter:

SI

Value:

5.31

Test group / Remarks:

10% MEK

Parameter:

EC3

Value:

5.88

Test group / Remarks:

10% MEK

Interpretation of results:

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

Conclusions:

The SI obtained for DPX-C (Di-Cloro-Di-p-Xililene) at 10% concentration showed a greater than three fold increase over the control value with an EC3 value found to be 5.88%. Therefore, DPX-C (Di-Cloro-Di-p-Xililene) demonstrates moderate sensitiser potential in the local lymph node assay.

Executive summary:

This study was conducted to evaluate the skin sensitisation potential of DPX-C (Di-Cloro-Di-p-Xililene) in CBA/J strain mice in compliance with the OECD test guidelines for the local lymph node assay (LLNA).

A preliminary assay was conducted using treatment conditions similar to the main assay, in order to identify the appropriate test concentrations for the sensitisation assay.

Five groups of mice (each comprising 5 females) were selected for the main experiment. Based on the results from the preliminary assay, three groups were treated with DPX-C (Di-Cloro-Di-p-Xililene) at concentrations of 1%, 5% and 10% (w/v) in methyl ethyl ketone (MEK) for three consecutive days (days 0, 1 and 2) on the dorsum of both ears (25mL per ear). In addition, one group served as the vehicle control and was treated with methyl ethyl ketone (MEK) and another group served as the positive control and was treated with HCA (a-hexylcinnamaldehyde)at a concentration of 25% (v/v) in methyl ethyl ketone (MEK).

Group mean body weights of treated animals were comparable with the control group and there were no indications of skin irritation at the treatment site or systemic toxicity in DPX-C (Di-Cloro-Di-p-Xililene) treated animals.

On day 5, the uptake of intravenously injected³H-methyl thymidine into the auricular (local) lymph nodes draining at the site of chemical application was measured (5 hours post-administration) to assess the lymph node proliferative response. Stimulation indices (SI) for the 1%, 5% and 10% (w/v) in methyl ethyl ketone (MEK) of DPX-C (Di-Cloro-Di-p-Xililene) treated groups were 1.63, 2.51 and 5.31, respectively.

The SI obtained forDPX-C (Di-Cloro-Di-p-Xililene)at 10% concentration showed a greater than three fold increase over the control value with an EC₃value found to be 5.88%. Therefore,DPX-C (Di-Cloro-Di-p-Xililene)demonstrates moderate sensitiser potential in the local lymph node assay.

Apositive response for HCA (SI = 11.40), in agreement with historical controls, confirmed the reliability of the test procedure.

Based on the results of this study, an indication of the classification forDPX-C (Di-Cloro-Di-p-Xililene) isas follows:

Globally Harmonized System of Classification and Labeling of Chemicals (GHS2015): Sub Category 1B.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The SI obtained forDPX-C (Di-Cloro-Di-p-Xililene)at 10% concentration showed a greater than three fold increase over the control value with an EC₃value found to be 5.88%. Therefore,DPX-C (Di-Cloro-Di-p-Xililene)demonstrates moderate sensitiser potential in the local lymph node assay.

Justification for classification or non-classification

The SI obtained for DPX-C (Di-Cloro-Di-p-Xililene) at 10% concentration showed a greater than three fold increase over the control value with an EC₃value found to be 5.88%. Therefore, DPX-C (Di-Cloro-Di-p-Xililene) demonstrates moderate sensitiser potential in the local lymph node assay.

Therefore according to Regulaion (EC) n. 1272/2008, Dichloro-p-cyclophane is classified as Skin Sens. 1B, H317.