Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 March 1992 - 27 May 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
not specified
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Study performed in 1993

Test material

Constituent 1
Chemical structure
Reference substance name:
2-bromo-6-(4-methylbenzoyl)pyridine
EC Number:
618-079-0
Cas Number:
87848-95-1
Molecular formula:
C13H10BrNO
IUPAC Name:
2-bromo-6-(4-methylbenzoyl)pyridine
Specific details on test material used for the study:
Identity: Compound 45W81.
Chemical name: 2-Bromo-6-( 4-toluoyl )pyridine.
Lot/Batch number: 310/C60
Expiry: 2 April 1993.
Purity: 99.8%.
Appearance: Off-white solid.
Storage conditions: Room temperature in the dark.
Date received: 2 April 1992.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
ANIMAL MANAGEMENT
Thirty healthy female nulliparous and non-pregnant albino guinea-pigs of the Dunkin/Hartley strain were obtained from D. Hall, Newchurch, Staffordshire, England.
The animals were in the weight range of 286 to 354 g on arrival and approximately six to seven weeks of age. All the guinea-pigs were acclimatised to the experimental environment for 12 days prior to allocation to the main study.
An additional six animals, from the same supplier, were used for the preliminary investigations.
The animals on the main study were allocated without conscious bias to two groups as follows:
10 Control animals, numbers 1430 to 1439
20 Test animals, numbers 1440 to 1459

The guinea-pigs were housed in groups of ten in suspended metal cages with wire mesh floors in Building R 17 Room 14.
A vitamin C enriched guinea-pig diet FDl and drinking water were provided ad libitum. Hay was given weekly.
The batch of diet used for the study was not analysed for chemical or microbiological contaminants.
However a 500 g sample of each batch of diet used in the study was retained at -20'C for future analysis if deemed necessary. If not informed to the contrary the sample will be discarded three months after the date of issue of the final report.
Results of routine physical and chemical examination of drinking water at source, as conducted usually weekly by the supplier, are made available to Huntingdon Research Centre Ltd. as quarterly summaries. Contaminants in drinking water were not thought to occur in sufficient quantities to adversely effect the study.
Animal room temperature was maintained at approximately 21 °C and relative humidity at 30 - 70%. These environmental parameters were recorded daily. Air exchange was maintained at approximately 15 air changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.
Each animal was identified by ear tattoo number. This number was unique within the HRC Industrial Toxicology Department throughout the duration of the study. Each cage was identified by a coloured label displaying the study schedule number, animal numbers and the initials of the Study Director and Home Office licensee.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: Acetone
Concentration / amount:
Compound 45W81, 7.5% w/w in 5% acetone in Alembicol D.
Route:
intradermal
Vehicle:
other: 50: 50 mixture of Freund's complete adjuvant and 5% acetone in Alembicol D
Concentration / amount:
Compound 45W81, 7.5% w/w in a 50: 50 mixture of Freund's complete adjuvant and
5% acetone in Alembicol D.
Route:
epicutaneous, occlusive
Vehicle:
other: acetone
Concentration / amount:
0.4 ml of Compound 45W81, 70% w/w in acetone
Day(s)/duration:
2
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Acetone
Concentration / amount:
Compound 45W81, 70% and 35% w/w in acetone
Day(s)/duration:
1
No. of animals per dose:
20
Positive control substance(s):
no
Remarks:
Results for Formalin from previous recorded data used, 1986 - 1991

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
70% and 35%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
One animal showed slight erythema (score of 1) at 24, 48 and 72h and slight oedema (score of 1) at 48 and 72h.
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
70% and 35%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
One animal showed slight erythema (score of 1) at 24, 48 and 72h and slight oedema (score of 1) at 48 and 72h.
Key result
Reading:
1st reading
Hours after challenge:
72
Group:
test chemical
Dose level:
70% and 35%
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
One of the two animals showed well defined erythema (score of 2) and slight oedema (score of 1) at 72h. The other animal showed slight erythema (score of 1) at 24, 48 and 72h and slight oedema (score of 1) at 48 and 72h.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
72
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
other: Historic data
Group:
positive control
Remarks on result:
positive indication of skin sensitisation

Any other information on results incl. tables

CLINICAL SIGNS

No signs of ill health or toxicity were recorded.

 

BODYWEIGHT

Bodyweight increases were recorded for all guinea-pigs over the period of the study.

 

INDUCTION

Intradermal injections

Necrosis was recorded at sites receiving Freund's Complete Adjuvant in test and control animals. Irritation was seen in test animals at sites receiving Compound 45W8 l, 7.5 % w /w in 5 % acetone in Alembicol D. Slight irritation was observed in control animals receiving 5% acetone in Alembicol D.

 

Topical application

Slight erythema was observed in test animals following topical application with Compound 45W81, 70 % w /w in acetone. Very slight erythema was seen in the control guinea-pigs.

 

CHALLENGE

The dermal reactions seen in two test animals were more marked than the controls. The dermal response seen in the remaining test animals were similar to the controls.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
According to GHS, for Category 1, 30% of animals need to show positive results and 15% in non-adjuvant studies Gunea pig studies. In this study, two out of twenty test group Guinea pigs showed evidence of skin sensitisation, so 10 % of animals.
One of the two animals showed well defined erythema (score of 2) and slight oedema (score of 1) at 72h.
The othe animal showed slight erythema (score of 1) at 24, 48 and 72h and slight oedema (score of 1) at 48 and 72h.
All 18 other animals showed no erythema and no oedema for all time points.

Therefore it is udnerstood that the GHS criteria for classification are not met.