2,2',6,6'-tetrabromo-4,4'-isopropylidenediphenol

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27th April - 5th June 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Tetrabromo Bisphenol-A, Lot # R6/FD2, was dermally applied to ten guinea pigs for a total of nine six-hour insult periods. A positive control group consisting of 10 guinea pigs was treated with 2 -4 dinitrochlorobenzene.

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

The study was conducted before the testing guidelines for LLNA (OECD 429) was available.

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): Tetrabromo Bisphenol-A
- Molecular formula (if other than submission substance): N/A
- Molecular weight (if other than submission substance): N/A
- Smiles notation (if other than submission substance): N/A
- InChl (if other than submission substance): N/A
- Structural formula attached as image file (if other than submission substance): see Fig. N/A
- Substance type: Monoconstituent
- Physical state: Solid, white powder
- Analytical purity: Not reported
- Impurities (identity and concentrations): Not reported
- Composition of test material, percentage of components: Not reported
- Isomers composition: Not reported
- Purity test date: Not reported
- Lot/batch No.: #R6/FD2
- Expiration date of the lot/batch: Not reported
- Radiochemical purity (if radiolabelling): N/A
- Specific activity (if radiolabelling): N/A
- Locations of the label (if radiolabelling): N/A
- Expiration date of radiochemical substance (if radiolabelling): N/A
- Stability under test conditions: Stable; "there was no apparent change in thephysical state of the test article or control article during adminstration"
- Storage condition of test material: Not reported

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Perfection Breeders, Inc, Douglassville, Penn. USA
- Age at study initiation: Not reported
- Weight at study initiation: 220 to 500 grams
- Housing: Two per cage, in stainless steel 1/2" wire mesh cages
- Diet (e.g. ad libitum): Wayne Guinea Pig Diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72F +/- 5F
- Humidity (%): Ambient
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 10 hours light: 14 hours dark

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

other: Moistened with 80% ethanol

Induction 2

Concentration / amount:

500 mg per induction site

Challenge

Challenge 1

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: Moistened with 80% ethanol

Challenge 2

Concentration / amount:

500 mg per induction site

No. of animals per dose:

Ten

Details on study design:

RANGE FINDING TESTS: N/A

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: One
- Exposure period: Six hours
- Test groups: One group of 10
- Control group: one group of ten exposed to 2-4 dinitrochlorobenzene
- Site: Dorsal area
- Frequency of applications: See below
- Duration: a total of three weeks
- Concentrations: 500 mg/site

B. CHALLENGE EXPOSURE
- No. of exposures: Eight (not including intial exposure; rotated between application sites, giving a total of three exposures per site )
- Day(s) of challenge: Every Monday, Wednesday, and Friday for three weeks
- Exposure period: Six hours
- Test groups: 10 guinea pigs
- Control group: 10 guinea pigs exposed to 2-4 dinitrochlorobenzene
- Site: Dorsal area (split into three application sites, and dosed on a rotating basis)
- Concentrations: 500 mg/site
- Evaluation (hr after challenge): Treated sites examined 7, 24, and 48 hours after each exposure

Challenge controls:

2,4 dinitrochlorobenzene: 1%/mL/site

Positive control substance(s):

yes

Remarks:

2,4 dinitrochlorobenzene

Results and discussion

Positive control results:

2,4 dinitrochlorobenzene elicited positive responses at challenges I and II

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

500 mg

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

rechallenge

Hours after challenge:

48

Group:

negative control

Dose level:

0 mg

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No

Remarks on result:

not measured/tested

Results 3

Key result

Reading:

rechallenge

Hours after challenge:

48

Group:

positive control

Dose level:

1% /ml/site

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

Erythema duing induction

Remarks on result:

positive indication of skin sensitisation

Any other information on results incl. tables

Table 1: Average Scores at 7, 24, 48 hours following Challenge I and II

	Challenge I						Challenge II
	Site I			Site II			Site I			Site II
Test article	7	24	48	7	24	48	7	24	48	7	24	48
Tetrabromobisphenol-A (500 mg)	0	0	0	0	0	0	0	0	0	0	0	0
DNCB (1%)	1	1	1	1	1.5	1	1	1	1.2	1	1	2

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Tetrabromo Bisphenol-A, Lot #R6-FD2, did not cause delayed hypersensitivity in guinea pigs.

Executive summary:

Tetrabromobisphenol-A, Lot # R6/FD2, was dermally applied to ten guinea pigs for a total of nine six-hour insult periods. A positive control group consisting of 10 guinea pigs was treated with 2,4 dinitrochlorobenzene. Approximately fourteen days after the last senstizing exposure, the animals were challenged in the same manner at both the site of sensitizing and a second challenge site. 48 hours after the first challenge, a second challenge was made. A positive reposnse was elicited by the animals receiving 2,4 dinitrochlorobenzene at challenges I and II. Erythema was observed during induction at 7 hours post doses 3 and 9, 24 hours post doses 3, 6, and 9, and 48 hours post doses 3, 6, and 9. No irritation was observed during induction or challenge periods with Tetrabromo Bisphenol-A.

Tetrabromo Bisphenol-A, Lot # R6/FD2, did not cause delayed hypersensitivity in guinea pigs.