Registration Dossier

Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
A sample of neutralised product from acid extraction before steam distillation (ISK8) was supplied to the laboratory in April 1982 for an assessment of its skin irritation and skin sensitising potential. This material had the following constituents 3-trifluoromethylpyridine (TF) 53.2%, 2-chloro-5-trifluoromethylpyridine (CTF) 23.2%, 2,6-Dichloro-3-trifluoromethylpyridine (DCTF) 5.9%. The remainder was water, sodium chloride, sodium fluoride and sodium hydroxide.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
Dunkin Hartley albino female guinea pigs were supplied by the Animal Breeding Unit, Imperial Chemical Industries PLC, Pharmaceuticals Division, Alderley Park, Macclesfield, Cheshire, UK. At the start of the experiment the guinea pigs were aged between 4 and 7 weeks and weighed 420-520g.

The guinea pigs were housed in suspended stainless steel mesh cages (370mm length x 320mm width x 200mm height). The floor and back of each cage were 12mm square stainless steel mesh, the sides were solid stainless steel and the front was polycarbonate (Makrolon). The animals were housed individually with two animals per cage. For this purpose the experimental cages were divided into two equal compartments by placing a solid metal partition within each cage and one animal was kept in each compartment.

The animals were fed ad libitum with Labsure RGP Guinea Pig Diet and allowed tap water ad libitum via an automatic water system.

The room in which the guinea pigs were held was maintained at a temperature of approximately 21°C with a relative humidity of 55%. Temperature and relative humidity were recorded constantly using a thermohygrograph. There were 10-20 air changes per hour and the light pattern was controlled to give alternate period of 12 hours light and 12 hours darkness. The guinea pigs were acclimatised to the animal laboratory for a minimum of six days immediately prior to the experiment.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, open
Vehicle:
other: dimethyl formamide
Concentration / amount:
Induction: 0.1ml of test substance as a 10% solution in dimethyformamide (DMF)
Challenge: 0.2ml. of test substances as a 10%, 1% and 0.1% solution in DMF.
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: dimethyl formamide
Concentration / amount:
Induction: 0.1ml of test substance as a 10% solution in dimethyformamide (DMF)
Challenge: 0.2ml. of test substances as a 10%, 1% and 0.1% solution in DMF.
No. of animals per dose:
10 female guinea pigs (6 pre-treated with test substance, 4 DMF controls)
Details on study design:
The sensitising properties of the material were assessed using a modified version of the ear/flank technique of Stevens (1967). A group of ten female guinea pigs was used – six test, four control. Each animal was given a number unique to the study, which was written on the cage card. The study involved two procedures, an induction of the response and a challenge of that response.

Induction

Approximately 0.1ml of the test substance, as a 10% (w/v) solution in dimethylformamide (DMF) was applied daily to the outer surface of the ears with a glass Pasteur pipette. This induction procedure was carried out on the six test animals on Days 1, 2 and 3. The four control animals were treated in the same way but with DMF alone.

Challenge

Four days later (Day 7), immediately prior to the challenge applications an area approximately 110mm x 50mm on each flank of all ten animals was clipped free of hair using veterinary clippers. The challenge application was then carried out using a range of three concentrations of the test substance (10%, 1% and 0.1% solutions in DMF). Approximately 0.2ml of each solution was applied using a glass Pasteur pipette to separate 10mm circular areas on both flanks of all ten Guinea pigs. On day 8, any erythema present at the challenge sites was rated on a six-point scale. Any erythema in the pre-treated animals in excess of that in controls was considered to note sensitisation.
Positive control substance(s):
no

Results and discussion

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
No erythema was seen in any animal, test or control, during the study period.

In conclusion, therefore, the neutralised product from acid extraction before steam distillation (ISK-8) is not sensitising to guinea pig skin. Since this process stream is chiefly made up of trifluoromethyl pyridines including 23.2% 2-chloro-5-trifluoromethyl pyridine (CTF) it is concluded that the study provides strong supporting evidence that CTF does not possess potential to cause skin sensitisation.
Executive summary:

No erythema was seen in any animal, test or control, during the study period.

In conclusion, therefore, the neutralised product from acid extraction before steam distillation (ISK-8) is not sensitising to guinea pig skin. Since this process stream is chiefly made up of trifluoromethyl pyridines including 23.2% 2-chloro-5-trifluoromethyl pyridine (CTF) it is concluded that the study provides strong supporting evidence that CTF does not possess potential to cause skin sensitisation.