Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-11-4 to 1997-11-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1993
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK.
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 200 to 242 g (males), 213 to 225 g (females)
- Fasting period before study: overnight fast immediately before dosing
- Housing: in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum (with exception of an overnight fasting before dosing and three to four hours after dosing)
- Water: ad libitum (with exception of an overnight fasting before dosing and three to four hours after dosing)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 22
- Humidity (%): 50 to 61
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
five males and five females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and mortality: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days
- Frequency of weighing: prior to dosing on Day 0 and on Days 7 and 14
- Necropsy of survivors performed: yes
Statistics:
Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidience and severity of all
abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.

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

Results and discussion

Preliminary study:
No signs of systemic toxicity or deaths were noted at 2000 mg/kg bw (one male and one female rat).
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths.
Clinical signs:
No signs of systemic toxicity.
Body weight:
All animals showed an expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test material, TODI, in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/ kg body weight.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted 24 February 1987) and Method B1 of Commission Directive 92/69/EEC (which constitues Annex V of Council Directive 67/548/EEC).

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single oral dose of test material as a suspension in arachis oil BP at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study. All animals showed an expected gain in bodyweight during the study. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CE strain was found to be greater than 2000 mg/kg body weight.