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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
between the 1st October and 7th October 1991.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
Principles of method if other than guideline:
The skin irritation potential of 45W81 (2-bromo-6-(4-toluoyl)pyridine), the stage 1 intermediate in the Acrivastine process, has been studied in the New Zeal and White rabbit. The test article was applied once to abraded or intact skin of New Zealand White rabbits, for 4 hours, as 500 mg/site of wetted material.
GLP compliance:
yes

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:
45W81 (2-bromo-6-(4-toluoyl) pyridine), batch 310/C60
The test article was stored in the dark at room temperature.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Three female New Zealand White rabbits, approximately 16 weeks in age and in the weight range 3 - 4 kg, were supplied by Froxfield Farms, UK Ltd. The New Zealand White rabbit is the conventionally accepted laboratory animal used for this type of safety testing. The animals were housed in room 7, Building 88, East wing, under standard environmental conditions.
The rabbits were allowed to acclimatise for at least two weeks prior to the start of dosing and were individually housed in plastic cages.
Each animal was identified by an ear tag (unique to that animal) plus a six digit study number.
Pelleted diet (FDl Special Quality Control Diet, Batch 6041, Special Diet Services Ltd) and drinking water (Thames Water Authority) were provided ad libitum.

Test system

Type of coverage:
occlusive
Preparation of test site:
abraded
Vehicle:
water
Controls:
no
Amount / concentration applied:
Two aliquots of 500mg of 45W81 were wetted with distilled water
Duration of treatment / exposure:
The patches were removed after a 4 hour exposure period and the remaining test substance gently wiped off the animals back using a damp cloth.
Observation period:
All animals were observed on 1, 24, 48 and 72 hours after dosing.
Number of animals:
3
Details on study design:
EXPERIMENTAL DESIGN
Animal numbers 913681, 913682 and 913683 were used in this study. On the day prior to dosing the back of each animal was clipped free of hair using electric clippers. The area clipped extended approximately 5cm down each flank. On the day of dosing the clipped area was inspected and its condition noted. Four application sites, each approximately 3cm x 3cm in size, were delineated with indelible ink so that two sites were located on either side of the spinal column. Two of the sites were abraded longitudinally with a 25 gauge needle at 1cm intervals so that the stratum corneum was penetrated but the abrasions were not deep enough to cause haemorrhage. Two aliquots of test article were wetted with distilled water and loaded onto patches. These were then applied to two sites, one of which was abraded and the other intact, on each rabbit. Each application site was covered with an occlusive patch made of tin foil and gauze and secured with adhesive tape. The two remaining skin sites received patches, each loaded with 500mg of water, which were secured in the same manner. A fitted jacket was secured around the animal to prevent removal of the patches. The patches were removed after a 4 hour exposure period and the remaining test substance gently wiped off the animals back using a damp cloth.

Observations/Procedures
All animals were observed on 1, 24, 48 and 72 hours after dosing.

Bodyweiqhts
Individual bodyweights were recorded on Day 1 and 7.

TERMINAL PROCEDURES
No terminal necropsy of these animals was performed. No tissues were taken for histopathological examination.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Unscheduled Deaths
There were no unscheduled deaths.

Erythema and Eschar Formation
There was no erythema or eschar formation on any site.

Oedema Formation
There was no oedema formation on any site.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Administration of 45W81 (2-bromo-6-(4-toluoyl) pyridine) to the skin of three New Zealand White rabbits caused no evidence of skin irritation.
45W81 (2-bromo-6-(4-toluoyl) pyridine) would appear to be innocuous to the skin of the New Zealand White rabbit.