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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
December 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
no
Remarks:
Study pre-dates GLP
Type of study:
not specified
Justification for non-LLNA method:
Study available is over 12 years old.

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl N-[4-[(2-bromo-6-chloro-4-nitrophenyl)azo]phenyl]-N-(3-methoxy-3-oxopropyl)-β-alaninate
EC Number:
261-874-9
EC Name:
Methyl N-[4-[(2-bromo-6-chloro-4-nitrophenyl)azo]phenyl]-N-(3-methoxy-3-oxopropyl)-β-alaninate
Cas Number:
59709-38-5
Molecular formula:
C20H20BrClN4O6
IUPAC Name:
methyl N-[4-[(2-bromo-6-chloro-4-nitrophenyl)azo]phenyl]-N-(3-methoxy-3-oxopropyl)-β-alaninate
Test material form:
solid: granular
Details on test material:
Disperse Brown 19

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
Ten young female Hartley-Dunkin albino guinea pigs obtained from Redfern Animal Breeders, Jasons Farm, Old Hay, Brenchley, Kent were used for this study. They were conditioned to the laboratory environment for not less than 6 days and on the day before initial treatment they were weighed. At this time the body weights of the guinea pigs were within the range 300 - 430 g. Three animals were marginally over the body weight range required by the protocol.

Diet
The animals were allowed free access to amins water and food (Guinea pig Diet-Standard supplemented with Vit. C., BP Nutrition (U.K.) Ltd., Stepfield, Witham, Essex).

Environment
All animals were housed in a single air-conditioned room maintained at a temperature of 22 + 3°C, relative humidity 50 + 10% and exposed to natural lighting conditions. They were caged in groups of 2 in grid floor polypropylene boxes.

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, open
Vehicle:
N,N-dimethylformamide
Concentration / amount:
0.1 ml of a 10% w/v solution
Day(s)/duration:
3 days
Adequacy of induction:
not specified
Challenge
No.:
#1
Route:
epicutaneous, open
Vehicle:
N,N-dimethylformamide
Concentration / amount:
0.2 ml
10% w/v, 1% w/v and 0.1% w/v
Day(s)/duration:
1 day
No. of animals per dose:
6 animals
Details on study design:
The test article (0.1 ml of a 10% w/v solution in dimethylformamjde) was applied daily by means of a glass syringe to the outer surface of the ears of 6 guinea pigs (animal numbers 1 - 6) for three days
(days 1, 2 and 3). On Day 8, 0.2 ml of the challenge solutions (10% w/v, 1% w/v and 0.1% w/v in dimethylformamide) was applied topically to 1 cm diameter circular areas on the clipped flanks of each of the same 6 animals. Solutions of test article were also applied in the same way on Day 8 to the clipped flanks of control animals (animal numbers 7 - 10) which had no previous treatment on the ears. The-applications were made on both flanks of all 10 guinea pigs, with each concentration being applied to each flank. The highest concentration was applied closest to the posterior end of the animal while the lowest concentration was applied nearest the anterior end.
The erythema produced on each site was assessed 24 hours later (Day 9) and graded on a 6 point scale.
Challenge controls:
The highest concentration was applied closest to the posterior end of the animal while the lowest concentration was applied nearest the anterior end.
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10% w/v
No. with + reactions:
0
Total no. in group:
6
Clinical observations:
None specified
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1% w/v
No. with + reactions:
0
Total no. in group:
6
Clinical observations:
None specified
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1% w/v
No. with + reactions:
0
Total no. in group:
6
Clinical observations:
None specified
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10% w/v
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
None specified
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1.0% w/v
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
None specified
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.1% w/v
No. with + reactions:
0
Total no. in group:
4
Clinical observations:
None specified
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Skin reactions at challenge phase

Test article: Disperse Brown 19

Vehicle: dimethylformamide

Concentration: 10% w/v, 1% w/v and 0.1% w/v

Animal number and sex

Weight

(g)

Skin reactions assessed at 24 hours after application

10% w/v

1% w/v

0.1% w/v

1

2

3

4

5

6

7 control

8 control

9 control

10 control

410

410

430

321

308

318

340

355

344

351

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
No erythema was noted in any of the test or control animals. The test article was not considered to be a strong sensitiser.
Executive summary:

A study was carried out to determine the skin-sensitising potential of test article in the albino guinea pig. The study was performed in accordance with Standard Operating Procedures.

 

Ten young female Hartley-Dunkin albino guinea pigs were used for this study. They were conditioned to the laboratory environment for not less than 6 days and on the day before initial treatment they were weighed. At this time the body weights of the guinea pigs were within the range 300 - 430 g. Three animals were marginally over the body weight range required by the protocol.

 

The test article (0.1 ml of a 10% w/v solution in dimethylformamjde) was applied daily by means of a glass syringe to the outer surface of the ears of 6 guinea pigs (animal numbers 1 - 6) for three days (days 1, 2 and 3).

On Day 8, 0.2 ml of the challenge solutions (10% w/v, 1% w/v and 0.1% w/v in dimethylformamide) was applied topically to 1 cm diameter circular areas on the clipped flanks of each of the same 6 animals. Solutions of test article were also applied in the same way on Day 8 to the clipped flanks of control animals (animal numbers 7 - 10) which had no previous treatment on the ears. The applications were made on both flanks of all 10 guinea pigs, with each concentration being applied to each flank.

The highest concentration was applied closest to the posterior end of the animal while the lowest concentration was applied nearest the anterior end.

The erythema produced on each site was assessed 24 hours later (Day 9).

 

Results

No erythema was noted in any of the test or control animals. The test article was not considered to be a strong sensitiser.