tert-butyl peroxyneodecanoate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999-12-07 to 2000-01-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

1996

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Adequate data from a guinea pig maximization test is available.

Test material

Test material information

Constituent 1

Reference substance name:

tert-butyl peroxyneodecanoate

EC Number:

247-955-1

EC Name:

tert-butyl peroxyneodecanoate

Cas Number:

26748-41-4

Molecular formula:

C14H28O3

IUPAC Name:

Reaction products of neodecanoic acid (or neodecanoyl chloride derived from neodecanoic acid) and tert-butyl hydroperoxide

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg Germany
- Age at study initiation: approx. 4 weeks old
- Weight at study initiation: individual body weights < 500 grams
- Housing: group housing of 5 animals per labelled metal cage with wire-mesh floors and equipped with an automatic drinking system
- Diet: free access to standard guinea pig diet, including ascorbic acid (1000 mg/kg)
- Water: free access to tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 30-70 %
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

propylene glycol

Induction 2

Concentration / amount:

Induction (intradermal): 100 %
Induction (epicutaneous): 100 %
Challange (epicutaneous): 100 %

Challenge

Challenge 1

Route:

epicutaneous, semiocclusive

Vehicle:

propylene glycol

Challenge 2

Concentration / amount:

Induction (intradermal): 100 %
Induction (epicutaneous): 100 %
Challange (epicutaneous): 100 %

No. of animals per dose:

Experimental group: 10 females
Control group: 5 females

Details on study design:

RANGE FINDING TESTS: Practical feasibility of administration determined the highest starting-concentration for each route. The starting- and subsequent concentrations were taken from series: 100 % (undiluted), 50 %, 20 %, 10 %, 5 %, 2 %, 1 % and if needed, further lower concentrations using the same steps.
The test system and procedures were identical to those used during the main study, unless otherwise specified. The six animals selected were between 4 and 9 weeks old. No bdy weights were determined at termination.

MAIN STUDY
A. INDUCTION EXPOSURE
a) First induction (intradermal)
- No. of exposures: 1
- Exposure period: single treatment on day 1
- Test groups: A. A 1:1 w/w mixture of Freunds`Complete adjuvant with water for injection; B. The test substance at a 100 % concentration.; C. A 1:1 w/w mixture of the undiluted test substance and Freunds`Complete Adjuvant.
- Control group: treated with adjuvant and the vehicle
- Site: scapular region
- Frequency of applications: once
- Concentrations: 100 %

a) Second induction (epicutanous), 7 days after first induction
- No. of exposures: 1
- Exposure period: 48 hours
- Test groups: The scapular area was treated with 0.5 mL of a 100 % test substance concentration.
- Control group: treated with adjuvant and the vehicle
- Site: scapular region
- Frequency of applications: once
- Concentrations: 100 %

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 13 days after the epidermal exposure
- Exposure period: 24 hours
- Test groups: single treatment
- Control group: single treatment
- Site: flank
- Concentrations: 100 %
- Evaluation (hr after challenge): 24, 48 hours

Challenge controls:

No

Positive control substance(s):

yes

Remarks:

Alpha-hexylcinnamic aldehyde, tech. 85 %; Realiability check

Results and discussion

Positive control results:

A reliability check is carried out at regular intervals to check the sensititivity of the test system and the reliability of the experimental techniques.
The skin reactions in eight experimental animals observed in response to the 10 % test substance concentration in the challenge phase were considered indicative of sensitisation, based on the absence of any response in the control animals. These results lead to a sensitisation rate of 80 per cent to the 10 % concentration.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

9

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 9.0. Total no. in groups: 10.0.

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 %

No. with + reactions:

8

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 8.0. Total no. in groups: 10.0.

Results 5

Group:

positive control

Remarks on result:

other: not examined

Applicant's summary and conclusion

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

Taking into account the intensity of the responses and comparing theses with the skin reactions seen in the control animals, it was considered that hypersensitivity had been induced in nine (of the ten) experimental animals. The skin reactions as observed in the control animals were considered to be non-specific signs of irritation. These results indicate a sensitisation rate of 90 per cent.

Executive summary:

Tert.butyl peroxyneodecanoate (75 % in solvent) was tested in a Maximisation Test in albino guinea pig according to EU method B.6 and OECD guideline no. 406. Test substance concentrations selected for the main study were based on the results of a preliminary study. In the main study, ten experimental animals were intradermally injected with and epidermally exposed to a 100 % concentration. Five control animals were similarly treated, but with vehicle alone (water). Two weeks after the epidermal application all animals were challened with a 100 % test substance concentration and the vehicle.

In the challenge phase in response to the 100 % test substance concentration, skin reactions varying between grades 1 and 4 were observed in all experimental animals and skin reactions of grade 1 were observed in all control animals.

Eschar formulation was seen in the treated skin sites amoung the experimental animals.

Taking into account the intensity of the responses and comparing theses with the skin reactions seen in the control animals, it was considered that hypersensitivity had been induced in nine (of the ten) experimental animals. The skin reactions as observed in the control animals were considered to be non-specific signs of irritation. These results indicate a sensitisation rate of 90 per cent.