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Description of key information

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:
1988
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England
- Age at study initiation: Not indicated
- Weight at study initiation: 301-374g
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Induction:
7.5% w/w sodium bromide, technical grade in water (intradermal injection)
30% w/w sodium bromide, technical grade in water (topical application)

Challenge:
5% and 10% w/w sodium bromide, technical grade in water
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction:
7.5% w/w sodium bromide, technical grade in water (intradermal injection)
30% w/w sodium bromide, technical grade in water (topical application)

Challenge:
5% and 10% w/w sodium bromide, technical grade in water
No. of animals per dose:
20 in test group
20 in control group
Details on study design:
RANGE FINDING TESTS:
The irritancy of a range of dilutions following intradermal and topical application was investigated for the selection of suitable irritant concentrations for induction and non-irritant concentrations for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Two
- Exposure period: day 0 intradermal injection, day 7 topical application
- Site: scapular region
- Duration: 24 h for topical application
- Concentrations: 7.5% w/w sodium bromide, technical grade in water (intradermal injection), 30% w/w sodium bromide, technical grade in water (topical application)


B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: day 21
- Exposure period: 24 hours
- Site: scapular region
- Concentrations: 5% and 10% w/w sodium bromide, technical grade in water
- Evaluation (hr after challenge): 24h, 48h and 72h after challenge


OTHER:
Concentration Freunds Complete Adjuvant (FCA): 50% in water
Positive control substance(s):
yes
Remarks:
Formalin
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
7.5 % / 30 %, 10 % / 5 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 7.5 % / 30 %, 10 % / 5 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical signs .
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
7.5 % / 30 %, 10 % / 5 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 7.5 % / 30 %, 10 % / 5 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical signs .
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical signs .
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no clinical signs
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no clinical signs .

Result of pilot study:

Intradermal injection of different concentrations of sodium bromide resulted in slight to mild oedema and slight to necrotic erythema (see table 6.1.5/02-1).

Topical application of 5, 10, 20 and 30 % sodium bromide, technical grade showed localized dermal reactions in one of the animals treated with 20% of test substance. This reaction was reversible and skin appeared normal by 24 hours after treatment. All other animals did not show reactions after treatment.

Based on the results of the preliminary investigations, concentrations of 7.5% (w/w) and 30% (w/w) were selected for intradermal and topical induction and 10% and 5% (w/w) for topical challenge application.

Overall result of main study:

Sodium bromide, technical grade did not produce evidence of delayed contact hypersensitivity

Table A6.1.5/02-1          Results of pre-test with Sodium Bromide, technical grade, intradermal injection

 

Guinea-pig number

Concentration

[% w/w]

 

 

Score

 

  

1

2

 

4674/4679

10

D

E

O

8/12

N/N

2/2

8/10

N/N

2/2

 

7.5

D

E

O

8/10

2/2

1/1

8/10

1/1

1/1

 

5

D

E

O

6/8

2/2

1/1

6/6

1/1

2/2

 

2.5

D

E

O

6/6

2/2

1/1

6/6

1/1

1/1

 

1

D

E

O

4/4

1/1

1/1

4/4

1/1

1/1

 

0.5

D

E

O

4/4

1/1

1/1

4/4

1/1

1/1

 

0.25

D

E

O

4/4

1/1

1/1

4/4

1/1

1/1

 

0.1

D

E

O

4/4

1/1

1/1

4/4

1/1

1/1

 

vehicle control

(water)

D

E

    O

4/4

1/1

1/1

4/4

1/1

1/1

 

D: Diameter (mm)

E: Erythema (0-4 numerical scores)

O: Oedema (0-4 numerical scores)

N: Necrosis

1: score assessed day of injection

2: score assessed day 3 after injection

Table A6.1.5/02-2          Results of main study with Sodium Bromide, technical grade, challenge application

Treatment

Guinea-pig number

Erythema (E)

Oedema (O)

Score

Results

24 h

48 h

72 h

A

P

A

P

A

P

Freund´s

Treated control

5590

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5591

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5592

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5593

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5594

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5595

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5596

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5597

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5598

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5599

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5560

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5501

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5502

E

O

L1

0

0

0

0

0

0

0

0

0

0

0

n.d.

5503

E

O

L1

0

0

0

0

0

0

0

0

0

0

0

n.d.

5504

E

O

0

0

L1

0

0

0

0

0

0

0

0

0

n.d.

5505

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5506

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5507

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5508

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

5509

E

O

0

0

0

0

0

0

0

0

0

0

0

0

n.d.

 

Test

5510

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5511

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5512

E

O

0

0

L1

0

0

0

0

0

0

0

0

0

-

5513

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5514

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5515

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5516

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5517

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5518

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5519

E

O

0

0

L1

0

0

0

0

0

0

0

0

0

-

5520

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5521

E

O

L1

0

L1

0

0

0

0

0

0

0

0

0

-

5522

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5523

E

O

L1

0

0

0

0

0

0

0

0

0

0

0

-

5524

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5525

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5526

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5527

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5528

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

5529

E

O

0

0

0

0

0

0

0

0

0

0

0

0

-

A           Anterior site, exposed to 10% w/w sodium bromide, technical grade in distilled water

P            Posterior site, exposed to 5% w/w sodium bromide, technical grade in distilled water

L1          Localized dermal reaction, restricted to a small area of the challenge site

Results: +              positive

-                    negative

+/-         inconclusive

 

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
In this screening test performed with twenty guinea pigs, sodium bromide, technical grade did not produce evidence of delayed contact hypersensitivity. The test substance does not have to be classified and labelled with respect to skin sensitisation.
Executive summary:

Materials and Methods

The study was designed to assess skin sensitisation potential of Sodium Bromide, technical grade. The intradermal and topical irritancy of a range of dilutions of sodium bromide, technical grade was investigated to identify (a) irritant test substance concentrations suitable for the induction phase of the main study and (b) non-irritant concentrations by the topical route of administration for the challenge phase. Based on the results of this preliminary investigation concentrations of sodium bromide for the main study were selected. For the main study twenty guinea pigs were treated with the test substance intracutaneously (day 0) and epicutaneously (day 7) for induction and epicutaneously (day 21) for challenge.

Results and Discussion

The dermal reactions seen in the test animals are similar to those seen in the control animals.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Key study performed in accordance with OECD Guideline 406. 20 Dunkin-Hartley Guinea-pigs were treated with technical sodium bromide to determine skin sensitisation potential of the substance.

Topical application of 5, 10, 20 and 30 % sodium bromide, technical grade showed localized dermal reactions in one of the animals treated with 20% of test substance. This reaction was reversible and skin appeared normal by 24 hours after treatment. All other animals did not show reactions after treatment. Based on the results of the preliminary investigations, concentrations of 7.5% (w/w) and 30% (w/w) were selected for intradermal and topical induction and 10% and 5% (w/w) for topical challenge application.

Induction: A 4 cm x 6 cm area of dorsal skin on the scapular region was clipped free of hair with electric clippers. Three pairs of intradermal injectios were made simultaneously into this area. One week after the injections, the same interscapular area was clipped and shaved free of hair. A 2 cm x 4 cm patch of Whatman No.3 paper was saturated with sodium bromide, technical grade, 30% w/w in distilled water, placed on the shaved skin area and covered with impermeable plastic adhesive tape. The dressing was left in place for 48 hours.

Intradermal injection of different concentrations of sodium bromide resulted in slight to mild oedema and slight to necrotic erythema.

Animals were challenged topically two weeks after the induction period. 0.2 ml of sodium bromide, technical grade, 10 and 5% w/w in distilled water was applied to an anterior and posterior site on the flank respectively. Patches were sealed for 24 hours

For the main study twenty guinea pigs were treated with the test substance intracutaneously (day 0) and epicutaneously (day 7) for induction and epicutaneously (day 21) for challenge. Evaluations of sensitisation were made 24h, 48h and 72h after challenge. 20 Control animals were treated simultaneously without test material application. All animals were observed daily for signs of ill health of toxicity.

The dermal reactions seen in the test animals are similar to those seen in the control animals. 0/20 animals showed sensitisation reactions at any observation point. No clinical signs of toxicity were noted in any test animal during the period of the study.


Migrated from Short description of key information:
In a screening test performed with twenty guinea pigs, sodium bromide, technical grade did not produce evidence of delayed contact hypersensitivity (0/20 sensitisation rate).

Justification for classification or non-classification

Based on the experimental results of the Guinea pig maximisation test, sodium bromide is not classified for sensitization.