Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 January 2011 to 08 February 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study was conducted in accordance with OECD Guideline 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 17 December 2001). This study was also performed in compliance with UK GLP standards (Schedule 1, Good Laboratory Practice Regulations 1999 (SI 1999/3106 as amended by SI 2004/0994)).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identification: 3-trifluoromethylaniline
Description: Extremely pale yellow liquid
Batch Number: 101009
Purity: 99.66 %
Date Received: 25 October 2010
Storage Conditions: Room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Female Wistar (RccHan: WIST) strain rats were supplied by Harlan Laboratories U.K. Ltd, Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an accimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweight variation did not exceed +/- 20 % of the initial/mean bodyweight of any previously dosed animal(s).
The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 degrees celsius and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Doses:
300 mg/kg was chosen as the starting dose.
No. of animals per sex per dose:
5 animals
Control animals:
no
Details on study design:
Clinical observations were made 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Evaluation of data included identification of the number of animals that died during the study (or that were killed for humane reasons), and determination of the nature, severity, onset and duration of the toxic effects. If possible, the signs of evident toxicity were described. Evident toxicity referd to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality. Effects on bodyweights and abnormalities noted at necropsy were also identified.

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Signs of systemic toxicity noted were cyanosis, darkened eyes, pallor of the extremities, pilo-erection, hunched posture, ataxia, lethargy and pale faeces. Animals appeared normal five or eight days after dosing.
Body weight:
Individual bodyweights and bodyweight changes are given in Table 2.
Animals showed expected gains in bodyweight during the study, except for one animal which showed bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
Individual necropsy findings are presented in Table 3.

Any other information on results incl. tables

Table 1. Individual Clinical Observations and Mortality Data

Refer to attached "background material".

Table 2. Individual Bodyweights and Bodyweight Changes

Dose Level (mg/kg) Animal Number and Sex Bodyweight (g) at day     Bodyweight Gain (g) During Week
 0 7  14  1  2
             300  1 -0 Female  169  172  189  3  17
 2 -0 Female  163  172  189  9  17
 2 -1 Female  162  166  178  4  12
 2 -2 Female  174  183  193  9  10
 2 -3 Female  165  163  187  -2  24

Table 3. Individual Necropsy Findings

 Dose Level (mg/kg)  Animal Number and Sex  Time of Death  Macroscopic Observations
             300  1 -0 Female  Killed Day 14  No abnormalities noted
 2 -0 Female  Killed Day 14  No abnormalities noted
 2 -1 Female  Killed Day 14  No abnormalities noted
 2 -2 Female  Killed Day 14  No abnormalities noted
 2 -3 Female  Killed Day 14  No abnormalities noted

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be >300 mg/kg bodyweight.