Bis(2,4-di-tert-butyl-6-methylphenyl)ethyl phosphate

Endpoint summary

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:

1992-08-11 to 1993-01-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study (OECD Guideline 406)

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

adopted on 17-Jul-1992

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

other: Pirbright White

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY LTD. Animal Production, 4332 Stein / Switzerland
- Weight at study initiation: 323 to 423 g
- Housing: individually in Macrolon cages
- Diet: ad libitum standard guinea pig pellets
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3°C
- Humidity: 30 to 70%
- Photoperiod: 12 hrs light cycle

Route:

intradermal and epicutaneous

Vehicle:

other: vaseline, arachis oil, physiol. saline

Concentration / amount:

Intradermal Induction: test substance in arachis oil and adjuvant mixture: 5%
Epidermal Induction: test substance 50 % in vaseline
Epidermal Challenge: test substance 50 % in vaseline

Route:

epicutaneous, occlusive

Vehicle:

other: vaseline, arachis oil, physiol. saline

Concentration / amount:

Intradermal Induction: test substance in arachis oil and adjuvant mixture: 5%
Epidermal Induction: test substance 50 % in vaseline
Epidermal Challenge: test substance 50 % in vaseline

No. of animals per dose:

test group: 10 male and 10 female guinea pigs
control group: 5 male and 5 female guinea pigs

Details on study design:

RANGE FINDING TESTS
The concentration of the test compound for the induction and challenge periods were determined on four separate animals with concentrations of 1 %, 5 %, 10 %, 20%, 30% and 50%. The tested concentrations did not induce erythema reactions, therefore a concentration of 50% in vaseline was selected. No skin irritation was observed in the pretest. Therefore the application site was pretreated with 10% sodium-laurylsulfate (open application) 24 hours prior to the epidermal induction application. Concentration of test article for challenge was also 50% in vaseline.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: two-stage operation
- Exposure period: weeks 1 and 2
- Site: First, three pairs of intradermal injections into the neck region (adjuvant/saline; test item in vehicle; test item in vehicle plus adjuvant/saline) were given. Second, closed patch exposure over the injection sites one week later.

During weeks 3 and 4 no treatments were performed.

B. CHALLENGE EXPOSURE
- Exposure period: week 5
- Test and control groups: test substance in vaseline (w/w)
- Site: on the flank (occluded administration for 24 hrs)

Challenge controls:

A control group was treated with adjuvant and the vehicle during the induction period. During the challenge period the group was treated with the vehicle as well as with the test article (at least 10 animals) to check the maximum subirritant concentration of the test article in adjuvant treated animals.

Positive control substance(s):

no

Positive control results:

The sensitivity of the strain is checked once or twice a year with a known mild to moderate sensitiser, such as mercaptobenzothiazole, hexyl cinnamic aldehyde or potassiumdichromate.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50% test substance in vaseline

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

50% test substance in vaseline

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50% test substance in vaseline

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

50% test substance in vaseline

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% test substance in vaseline. No with. + reactions: 0.0. Total no. in groups: 10.0.

Interpretation of results:

not sensitising

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

The test substance was investigated for its sensitizing potential in a Maximization test according to OECD guideline 406 and under GLP requirements (CIBA-GEIGY Ltd., 924086, 1993). Pirbright White guinea pigs received two intradermal induction treatments with 5% in arachis oil and one epicutanous induction treatment with 50% in vaseline. For each injection, three pairs (adjuvant/saline; test item in vehicle; test item in vehicle plus adjuvant/saline) were given. Control animals were treated equally with test substance replaced by the vehicle. Epidermal challenge was performed by occlusive application for 24 h two weeks later (50% in vaseline). No skin reactions were observed either for control or test group animals. The sensitivity of the strain is checked once or twice a year with a known mild to moderate sensitiser, such as mercaptobenzothiazole, hexyl cinnamic aldehyde or potassiumdichromate. In conclusion, the test substance is therefore not considered to be a skin sensitizer in albino guinea pigs and does not require classification.

Migrated from Short description of key information:
Skin sensitization (OECD 406 & GLP, maximization test): not sensitizing (guinea pig, in vivo) (CIBA-GEIGY Ltd., 924086, 1993)

Justification for selection of skin sensitisation endpoint:
GLP-compliant guideline study

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Respiratory sensitization

No data

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available experimental test data is reliable and suitable for the purpose of classification under Directive 67/548/EEC. Based on the present data, classification for sensitization is not warranted under Directive 67/548/EEC.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification under Regulation (EC) No.1272/2008. Based on the present data, classification for sensitization is not warranted under Regulation (EC) No.1272/2008.