Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 26 jun 1985 to 22 nov 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to the standardised method and GLP.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Cited as Directive 84/449/EEC, B.1
Deviations:
yes
Remarks:
Variability in dose volume administration, not constant for all the doses studied.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS:
- Species: COMMON SPECIES: rat
- Strain: RAT STRAINS: Sprague-Dawley
- Sex: male/female
- Source: IFFA Credo (69510 St Germain sur l'Arbresle)
- Age at study initiation: 6-7 weeks
- Weight at study initiation: 150-200 g (male), 140-180 g (female)
- Fasting period before study: yes
- Housing : 2 or 5 animals per cage (34.2*25.2*18 cm)
- Food consumption: UAR entretien A04, ad libitum
- Water consumption:ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/-3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 10 removes
- Photoperiod (hrs dark / hrs light): no data

In-life dates: not specified

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: arachid oil
Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 1.3 g/100 ml
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

* Maximum dose volume applied: 15 ml/kg
* Dosage preparation: no
- Rationale for the selection of the starting dose: following a preliminary study.
Doses:
0, 100, 126, 156, 182, 195 mg/kg
No. of animals per sex per dose:
5
Control animals:
other: yes, vehicle only
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Behaviour and mortality: at 1, 2 and 4 hours after exposure, and then daily until day 14.
- weighing:at days -1, 0, 7 and 14, and when animals died.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organs observation at necropsy
Statistics:
Bliss method, Litchfield & Wilcoxon

Results and discussion

Preliminary study:
Doses: 50 mg/kg, no mortality observed
101 mg/kg: 50% of death
151 mg/kg: 25% of death
201 mg/kg: 75 % of death
316, 501, 1001, 2503 and 5005 mg/kg: 100% of mortality
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
128 mg/kg bw
Based on:
test mat.
95% CL:
111 - 149
Mortality:
100 mg/kg: 10% of death
126 mg/kg: 60%
156 mg/kg: 90%
182 mg/kg: 90%
195 mg/kg: 80%
Clinical signs:
At 100 mg/kg: after administration, all the animals showed prostration, ataxia, piloerection, pale tegument, 5/10 animals presented loss of reflexes, 7/10 hypothermia 4 hours after treatment. All this clinical signs were reversible within 5 days.
At 126 mg/kg, similar clinical signs were observed with prostration that persist in survival animals until day 7th.
At 156, 182 and 195 mg/kg clinical signs were prostration, loss of reflex, ptosis, pale tegument for surviving animals during first days
Body weight:
animals gain weight observation was short due to deaths of animals.
Gross pathology:
At 100 mg/kg: lungs were clear brown, digestive apparatus red with dark points on intestin.
At 126 mg/kg, 6 animals showed red lungs, pink pancreas.
At 156 and 182 mg/kg: all lungs were red and liver dark. In 3 animals, the spleen were black, slightly hard at touch and kidneys were dark.

Any other information on results incl. tables

Number of animals dead and time range within which mortality occurred
Dose Mortality (# dead/total) Time range of deaths (hours)
(mg/kg bw) Male Female Combined (%)
50 0/2 0/2 0 /
101 1/2 1/2 50 14 d
151 1/2 0/2 25 14 d
201 2/2 1/2 75 24 h
316 2/2 2/2 100 1h (M), 4 h (F)
501 2/2 2/2 100 1 h
1001 2/2 2/2 100 1 h
2503 2/2 2/2 100 1 h
5005 2/2 2/2 100 1 h

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
p-trifluoromethylaniline is toxic by oral route.
This substance is classified T R25 according to Annex VI of the directive 67/548/EC and acute tox Cat. 3 H301: toxic if swallowed, based CLP criteria.
Executive summary:

In an acute oral toxicity study (Hazleton, 1985), groups of fasted, 6-7 weeks old Sprague-Dawley rats males and females (5/sex) were given a single oral dose of p-trifluoromethylaniline (purity >=98.5%) in arachid oil at doses 0, 100, 126, 156, 182, 195 mg/kg bw and observed for 14 days.
 Oral LD50 Combined = 128 mg/kg bw (111-149 mg/kg).
Based on these results, p-trifluoromethylaniline is considered as toxic by oral route and classified T R25 according to the 67/548/EC directive.

It is classified acute tox. Category 3 (H301), based on CLP criteria.