Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 8 jul 1985 to 19 aug 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was performed according to the standardised method but no data about GLP.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS:
- Species: rabbit
- Strain: New Zealand White
- Source: Charles River : F 76410 - Saint-Aubin-lès-Elbeuf ; E.G.A.V. : Saint-Mars-d'Egrenne - F 61350 - Passais-la-Conception ; Elevage Scientifique des Dombes : Roman - F 01400 - Chatillonsur-Chalaronne.
- Age at study initiation: no data
- Weight at study initiation: 2.5 kg (± 200 g)
- Housing : The rabbits are kept in individual polystyrene cages, measuring 540 x 360 x 315 mm with a perforated polystyrene floor in a ventilated and air conditioned room. Lighting is artificial for 12 hours per day (7.30 a.m. - 7.30 p.m.).
- Diet : 150 g of complete maintenance food (granulés Lapin Entretien "112" UAR, 91360 - Villemoisson / Orge) is provided per rabbit and per day.
- Water :ad libitum automatically (softened and filtered water : 15 µ)
- Acclimation period (durée): at least 8 days. Animals were vaccinated against the Myxomatosis (Lyomyxovax, Institut Mérieux).

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): 20°C +/-3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 to 14 times per hour (pre-filtered air: 5-10 µ)
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: day of application 16 jul 1985. Observation period not done.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: according to the guideline, the no treated area around the application site served as control
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hour(s)
Observation period:
no data
Number of animals:
6
Details on study design:
TEST SITE:
- Preparation of test site: a preparation of 14*14 cm were clipped on the back and on the flank with a fine toothed electric clipper the day before the
application. A precise cut was achieved without irritating the skin mechanically. After a rest period of 24 hours, only animals with perfectly healthy
intact skin showing no macroscopic sign of irritation were retained.
- Area of exposure: the substance was applied on a codex hydrophilic eight layer gauze pad about 2.5 cm square (6.25 cm2)
- Type of wrap if used: The test substance and the gauze pad are held in contact with the skin with a semi-occlusive patch : 10 cm wide adhesive
perforated tape (Peloplast : M.S.R.) applied on a crimped gauze bandage (Creplux-Molinier) covering more particularly the whole clipped surface
(to avoid possible orthoergic reactions) and wrapped around the animal (without blocking the respiratory and abdominal movements

REMOVAL OF TEST SUBSTANCE:
- Washing: After these 4 hours of exposure, the bandages are removed, and if necessary the excess of the test substance which has not penetrated
is wiped with a gauze pad moistened with deionized water (or a non-irritant)

- Time after start of exposure: 4 hours

SCORING SYSTEM: macroscopic examinations for cutaneous primary irritation were evaluated after removal of the gauze pad (4 hours exposure)
on time 1h, (5h after the application of the substance) 24, 48 and 72h. The scale used for cotation of erythema and oedema formations is conformed with EU guideline.
Scoring interpretation were done according to appendix VI of directive 79/831.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.44
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: 24h: 0.67; 48h: 0.33; 72h: 0.33 mean established for 6 animals.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not concerned

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test:

 

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 2

 60 min

0/0/0/0/0/0

0/0/0/0/0/0

 24 h

0/0/1/2*/0/1

0/0/0/0/0/0

 48 h

0/0/0/1*/0/1

0/0/0/0/0/0

 72 h

0/0/0/1*/0/1

0/0/0/0/0/0

Average 24h, 48h, 72h

0.44

0

Reversibility**

n for 2 animals

/

Average time (unit) for reversion

/

/

*: reaction out of application area 

** Reversibility: n. = not reversible

 

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Not irritating
Executive summary:

In a primary dermal irritation study (Hazleton, 1985), 6 rabbits were dermally exposed to p-trifluoromethylaniline (>=98.5%) for 4 hours to 6.25 cm2 of dorsal/flank skin. Test site was covered with a semi-occlusive patch for 4 hours. Animals then were observed 1, 24, 48 an 72 hours after removal the substance.
Irritation was scored following the erythema and oedema scale of EU guideline.

The mean value of erythema score was 0.44 without complete reversibility after 72h. No oedema effects were observed.
In this study, p-trifluoromethylaniline (>=98.5%) is slightly irritating but not a dermal irritant to the skin based on EU classification criteria.