Formaldehyde, reaction products with phenol heptyl derivs. and 1,3,4-thiadiazolidine-2,5-dithione

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 August 1991 to 26 September 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid method equivalent to OECD 406 and the study was conducted under GLP conditions.

Justification for type of information:

Study conducted prior to introduction of LLNA and in vitro and in chemico tests.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

Acetone used as the vehicle and to remove residual test material

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

Study conducted prior to introduction of LLNA and in vitro and in chemico tests.

Test material

Test material information

Constituent 1

Reference substance name:

OS# 89776

IUPAC Name:

OS# 89776

Test material form:

liquid: viscous

Details on test material:

- Physical state: brown viscous liquid
- Storage condition of test material: sealed contained at room temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Murphy Breeding Laboratories Inc, Plainfield, Indiana
- Age at study initiation: young adult
- Weight at study initiation: 337 to 387 grams
- Housing: individual suspended wire-mesh cages
- Diet (e.g. ad libitum): Purina GP chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 25
- Humidity (%): 48 to 85
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To: 20 august 1991 to 26 September 1991

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

other: acetone

Induction 2

Concentration / amount:

50%

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: acetone

Challenge 2

Concentration / amount:

50%

No. of animals per dose:

12 for the induction, challenge and re-challenge with the test material
6 naive animals for the challenge
6 naive animals for the re-challenge

Details on study design:

RANGE FINDING TESTS:
Primary irritation of the test substance was determined by single applications at 5, 10, 15, 25, 50 and 100% after dissolving in acetone at 0.4 ml/site. Doses were applied under gauze patches secured in place with tape. Three test sites per animal were used and exposure was for six hours. residual test material was removed using tissue moistened with acetone instead of water or mineral oil because the latter two were ineffective.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 100%
- Control group: dinitrochlorobenzene 0.25% in 80% ethanol
- Site: shaved flank
- Duration: 1 week between exposures

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 14 and 21
- Exposure period: 6 hours
- Test groups: 50% in acetone
- Control group: dinitrochlorobenzene 0.1% in 80% ethanol
- Site: anterior flank
- Concentrations: 50%
- Evaluation (hr after challenge): 24 and 48 hours

OTHER:

Challenge controls:

6 naive animals for the challenge and a further 6 naive animals for the re-challenge

Positive control substance(s):

yes

Remarks:

dinitrochlorobenzene

Results and discussion

Positive control results:

The sensitization index was calculated to be 5/6 (83%) following challenge dosing. The irritation indeces were 1.6 and 1.3 at 24 and 48 hours.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

50%

No. with + reactions:

1

Total no. in group:

12

Clinical observations:

None

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 1.0. Total no. in groups: 12.0. Clinical observations: None.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

2

Total no. in group:

12

Clinical observations:

None

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 2.0. Total no. in groups: 12.0. Clinical observations: None.

Any other information on results incl. tables

Incidence of dermal Responses at Challenge

Group	Material	Interval	Dermal Scores					No. of Animals	Irritation Severity Index
			0	+/-	1	2	3
Test	50% in acetone	24	1	10	1	0	0	12	0.5
	50% in acetone	48	4	8	0	0	0	12	0.3
Naïve Control I	50% in acetone	24	5	1	0	0	0	6	0.1
	50% in acetone	48	5	1	0	0	0	6	0.1
Positive Control	0.1% DNCB	24	0	1	1	4	0	6	1.6
	0.1% DNCB	48	0	1	4	1	0	6	1.1

 

 

Incidence of dermal Responses at Re-challenge

Group	Material	Interval	Dermal Scores					No. of Animals	Irritation Severity Index
			0	+/-	1	2	3
Test	50% in acetone	24	4	6	2	0	0	12	0.4
	50% in acetone	48	4	7	1	0	0	12	0.4
Naïve Control II	50% in acetone	24	5	1	0	0	0	6	0.1
	50% in acetone	48	5	1	0	0	0	6	0.1

 

 

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is not a skin sensitiser (2/12 sensitisation rate)

Executive summary:

Test Guideline

OECD Guideline 406

Method and materials

A test group of 6 male and 6 female Hartley albino guinea pigs was dosed topically with the test material (100%) one time per week for three weeks for a total of three induction exposures. The duration of the exposures was 6 hours. Two weeks after the last induction exposure Test group animals were challenge dosed for detection of sensitisation by topical application of a known non-irritating concentration of the test material (50% in acetone) to previously unexposed areas of the skin. One week after challenge dosing, the Test Group animals were rechallenged to confirm the initial challenge results.

A positive control group of 3 males and 3 females was included to demonstrate the reliability of the test system.

Naïve control groups I and II of 3 males and 3 females were dosed only at challenge and rechallenge respectively in the same manner as the Test Group and served as irritation controls.

Reactions to challenge and rechallenge dosing were evaluated at approximately 24 and 48 hours after completion of exposure. Body weights and clinical observations were recorded prior to study initiation and at termination.

Results

There were no deaths, clinical findings or remarkable body weight changes.

The positive control material, dinitrochlorobenzene, was demonstrated to be an extreme sensitizing agent in albino guinea pigs under the conditions of this study based on the Sensitization Incidence Index of 83%, thereby demonstrating the reliability of the test system.

There was one reaction in the Test Group that exceeded the highest reaction in the Naive Control Group I, following dosing with 50% w/v concentration of the test material in acetone. The Sensitization Incidence Index was calculated to be 8% for the Test Group following challenge dosing. There were two sensitization reactions (2/12) in the Test Group following rechallenge dosing with a 50% w/v concentration of the test material in acetone. The Sensitization Incidence Index was calculated to be 17% for the Test Group following rechallenge dosing.

Conclusion

In accordance with CLP Regulation (EC) No 1272/2008 the test material is not classified for skin sensitisation