[2-(Isopropoxycarbonyloxy)-benzoyl]-benzoylperoxide

Endpoint summary

Description of key information

In order to assess the potential to induce skin sensitisation of CD08467, available data from CD08679 (source substance) was used in read-across approach. The source substance was tested negative in an in vivo local lymph node assay conducted in accordance with OECD test guideline 429. Based on this result, the target substance CD08467 is not considered to be a skin sensitiser. This result is supported by a mouse ear swelling test conducted with the target substance. In this study, CD08467 does not present any sensitising properties.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For justification of read-across please refer to the read-across statement in IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Positive control results:

The positive-control substance exceeded (5.69) the stimulation index of 3 confirming the reliability of the test system. See Table 3 in box "Any other information on results incl. tables".

Key result

Parameter:

SI

Remarks:

mean of 8 animals

Value:

0.51

Variability:

SD = 0.34

Test group / Remarks:

2.5% test item

Key result

Parameter:

SI

Remarks:

mean of 8 animals

Value:

0.57

Variability:

SD = 0.41

Test group / Remarks:

5% test item

Key result

Parameter:

SI

Remarks:

mean of 8 animals

Value:

0.52

Variability:

SD = 0.47

Test group / Remarks:

10% test item

Cellular proliferation data / Observations:

DETAILS ON STIMULATION INDEX CALCULATION
For groups 2 to 6, an individual Stimulation Index (SI) was calculated for each animal, as the ratio between the individual DPM of treated animals versus the mean DPM of the vehicle control group (group 1). Then for each of the groups 2 to 6, a mean SI was calculated.
Stimulation Index (mean) of 0.51, 0.57 and 0.52 was calculated in response to CD08479 2.5%, 5% and 10% formulated in gel, respectively.
Stimulation Index (mean) of 0.25 was calculated for the placebo group (group 2), statistically significant when compared to group 1 (negative control group) following Dunnett’s test.
Stimulation Index (mean) of 5.69 was calculated for the positive control group (HCA 25%), statistically significant when compared to group 1 (negative control group) following Dunnett’s test, which demonstrated the performance and the reliability of the assay (SI ≥ 3).

CLINICAL OBSERVATIONS:
No abnormal clinical signs were observed in any treated-groups during the in-life part of this study.

CUTANEOUS REACTIONS:
No cutaneous reaction (erythema or edema) was observed in groups 1 to 5.
In group 6, treated with positive control HCA at 25%, discrete erythema was observed on Days 1 to 3 in 5/8 females, on Days 2 and 3 in 2/8 females and discrete to slight erythema was observed on Days 1 to 3 in 1/8 female. On Day 6, these reactions were no longer visible.

EAR SWELLING MEASUREMENT:
There was no increase of ear thickness observed between Day 1 (before treatment) and Day 6 (before intravenous injection of 3[H] MT) for any group

BODY WEIGHTS
No effect on the body weight was observed in any treated-group.

Chemical analyses

Analytical controls of CD08479 2.5%, 5% and 10% formulated in gel indicated that homogeneity and target concentrations were attained, within target ranges (100.00 ±10%; analytical method for active ingredient assay Reference RDS.03.ATP.03616.R01), and that the pharmaceutical dosage forms were stable for at least 3 weeks, covering the study duration.

Table 3: Results on Simulation Index

	Concentration of test item in applied formulation (%)				Positive control HCA
	Placebo	2.5	5	10	25%
Group number	2	3	4	5	6
N=number of date available	7	8	6	7	6
LLNA Concentration series (%)	NA	25	50	100	NA
SI (Mean)	0.25	0.51*	0.57	0.52	5.69*
Standard deviation	0.08	0.34	0.41	0.47	5.10

*: statistically significant when compared to vehicle group (5% significant level).

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, under the conditions of this study, the test item CD08479 formulated in gel is not considered to be a skin sensitiser

Executive summary:

In a dermal sensitization study conducted according to OECD 429 with the test item CD08479 formulated in gel and dissolved in AOO (4:1 (v/v) acetone/olive oil, young adult female CBA/JRj mice (8 per dose group) were treated CD08479 2.5%, 5% and 10% gel or Hexyl Cinnamic Aldehyde (HCA, 25% in AOO; positive control) at a constant dosing volume of 25μL on the dorsum of each ear, for three consecutive days. Simulation index along with other parameters including morbidity and mortality, clinical signs, cutaneous reactions, ear swelling and body weight were evaluated. During the study, no mortality or abnormal effects were observed on the female mice. However, discrete to slight erythema were observed on Days 1 to 3 for animals of positive control group (HCA). Stimulation Index of 0.51, 0.57 and 0.52 was calculated in response to CD08479 2.5%, 5% and 10% formulated in gel, respectively.

Based on these results, the test item did not show any potential for skin sensitization up to the concentration of 10% and thus is categorized as a non-skin sensitizer under UN GHS Criteria.

This information is used in a read-across approach in the assessment of the target substance. 

For justification of read-across please refer to the attached read-across statement (see IUCLID section 13).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In order to assess the potential to induce skin sensitisation of CD08467, available data from CD08679 (source substance) was used in read-across approach. For read-across justification see IUCLID section 13. The source substance was tested negative in an in vivo local lymph node assay conducted in accordance with OECD test guideline 429. Based on this result, the target substance CD08467 is not considered to be a skin sensitiser. This result is supported by a mouse ear swelling test conducted with the target substance. In this study, CD08467 does not present any sensitising properties.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on available data, CD08467 does not warrant classification for skin sensitisation.