Cyclohexylidenebis[tert-butyl] peroxide

Endpoint summary

Description of key information

Cyclohexylidenebis[tert-butyl]peroxide, as a 50 % w/v formulation in Squibb mineral oil, was tested for skin sensitizing properties in a Buehler assay with guinea pigs. The incidence and severity of the responses in the test group were essentially comparable to those produced by the vehicle control group indicating that sensitization had not been induced.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-04-10 to 1996-05-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted 17 July 1992

Deviations:

no

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

The study was conducted in 1992 when the LLNA was not an established testing method yet.

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., P.O. Box 29176; Indianapolis, Indiana 46229
- Age at study initiation: young adult
- Weight at study initiation: 373 to 681 g
- Housing: individually housed in wire mesh suspension cages
- Diet: teklad guinea pig diet; ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

Route:

epicutaneous, occlusive

Vehicle:

other: Squibb mineral oil

Concentration / amount:

- Induction: 50 % of the test item; undiluted: vehicle control

Route:

epicutaneous, occlusive

Vehicle:

other: Squibb mineral oil

Concentration / amount:

- Challenge: 50 % of the test item; 50 % of the vehicle

No. of animals per dose:

10 guinea pig per sex

Details on study design:

RANGE FINDING TESTS: The irritation potential of the test item at levels of 50 %, 25 %, 10 % and 5 %, was evaluted in a single group of four animals, such that each animal in a given pilot group was exposed to the same levels. In additional pilot, repeating the concentrations evaluated in pilot 1 plus four additional concentrations of 2.5 %, 1 %, and 0.5 % and undiluted Squibb mineral oil. All formulations were prepared w/v in Squibb mineral oil. The 50%, 25 %, 10 %, and 10 %, and 5 % formulation produced grades of +/-. The 2.5 %, 1 %, and 0.5 % formulations and the undiluted Squibb mineral oil produced grades of 1 and +/-.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: six-hour exposures (+/- 15 minutes)
- Test groups: 50 % of the test item
- Control group: undiluted vehicle
- Site: left shoulder
- Frequency of applications: thrice (once every seven days for fourteen days)
- Duration: six hour
- Concentrations: 50 %

B. CHALLENGE EXPOSURE
- No. of exposures: 3
- Day of challenge: 28
- Exposure period: once
- Test groups: 50 % of the test item
- Control group: 50 % of the test item
- Site: left flank
- Concentrations: 50 %
- Evaluation (hr after challenge): 24, 48 hour

Challenge controls:

no

Positive control substance(s):

yes

Remarks:

historical data

Positive control results:

The animals were induced by 1 exposure with 0.3 % (ethanol) 1-chloro-2,4-dinitrobenzene. The animals were induced by 3 exposures at weekly intervals with 2.5 % (ethanol) alpha-hexylcinnamaldehyde.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50 %

No. with + reactions:

9

Total no. in group:

20

Clinical observations:

slight but confluent, or moderate patchy erythema

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50 %

No. with + reactions:

0

Total no. in group:

20

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

50 %

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

slight but confluent, or moderate patchy erythema

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

50 %

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

slight but confluent, or moderate patchy erythema

Group:

positive control

Remarks on result:

not measured/tested

Interpretation of results:

GHS criteria not met

Conclusions:

Following primary challenge using cyclohexylidenebis[tert-butyl]peroxide, as a 50 % w/v formulation in Squibb mineral oil, the incidence of grade 1 responses in the test group (9 of 20) was compared to that of the vehicle control group (4 of 10). The incidence and severity of these responses in the test group were essentially comparable to those produced by the vehicle control group indicating that sensitization had not been induced.

Executive summary:

Cyclohexylidenebis[tert-butyl]peroxide was tested in the Buehler test with guinea pigs according to OECD guideline no. 406. A 50 % w/v concentration of the test item, in Squibb mineral oil was chosen for occlusive epidermal induction of the test group. This level was chosen as the highest concentration causing no greater than mild to moderate primary irritation. Undiluted Squibb mineral oil was utilized at induction for the vehicle control group. The procedure was repeated at the same site once every seven days for fourteen days for a total of three approximate six-hour exposures. A 50 % w/v concentration of cyclohexylidenebis[tert-butyl]peroxide, in Squibb mineral oil was chosen for epidermal application at primary challenge for the test group and the vehicle control group. This level was chosen as the highest concentration causing no more than slight primary irritation. Following primary challenge using cyclohexylidenebis[tert-butyl]peroxide, as a 50 % w/v formulation in Squibb mineral oil, the incidence of grade 1 responses in the test group (9 of 20) was compared to that of the vehicle control group (4 of 10). The incidence and severity of these responses in the test group were essentially comparable to those produced by the vehicle control group indicating that sensitization had not been induced.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Cyclohexylidenebis[tert-butyl]peroxide was tested in the Buehler test with guinea pigs according to OECD guideline no. 406. A 50 % w/v concentration of the test item, in Squibb mineral oil was chosen for occlusive epidermal induction of the test group. This level was chosen as the highest concentration causing no greater than mild to moderate primary irritation. Undiluted Squibb mineral oil was utilized at induction for the vehicle control group. The procedure was repeated at the same site once every seven days for fourteen days for a total of three approximate six-hour exposures.

A 50 % w/v concentration of cyclohexylidenebis[tert-butyl]peroxide, in Squibb mineral oil was chosen for epidermal application at primary challenge for the test group and the vehicle control group. This level was chosen as the highest concentration causing no more than slight primary irritation.

Following primary challenge using cyclohexylidenebis[tert-butyl]peroxide, as a 50 % w/v formulation in Squibb mineral oil, the incidence of grade 1 responses in the test group (9 of 20) was compared to that of the vehicle control group (4 of 10). The incidence and severity of these responses in the test group were essentially comparable to those produced by the vehicle control group indicating that sensitization had not been induced.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin sensitisation, the test item does not require classification according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.