Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study performed according to OECD Guideline 401 without any deviation

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
dated 24 February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
dated 31 July 1992
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
whitish powder
Details on test material:
- Storage condition of test material: Room temperature
- Manufacturing date: February 1995
- Expiration date: February 1997
- Purity test date: 30 October 1996
Specific details on test material used for the study:
Date of receipt: 06 July 1995
Name as cited in the report: TECHNICAL AMITROLE

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Credo, 69210 L'Arbresle, France
- Age at study initiation: ca. 6 weeks
- Weight at study initiation: 184 ± 7 g for males; 142 ± 12 g for females
- Fasting period before study: ca. 18 hours before dosing
- Housing: Animals were housed by group of five of the same sex in polycarbonate cages during the treatment period.
- Diet (e.g. ad libitum): A04 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France), ad libitum
- Water (e.g. ad libitum): Drinking water filtered by a F.G. Millipore membrane (0.22 micron), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 2 °C
- Humidity: 30-70%
- Air changes: 12/hour
- Photoperiod: 12 hours dark / 12 hours light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no.: 5698

DOSAGE PREPARATION: On the day of treatment, the test substance was prepared in distilled water.
Doses:
2000 and 10000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: historical data
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations and mortality were recorded frequently during the hours following each administration of the test substance, and then once daily for 14 days. Animals were weighed individually just before administration of the test substance on Day 1 and then on Days 8 and 15.
- Necropsy of survivors performed: Yes; on Day 15, all animals were killed by CO2 inhalation in excess and a macroscopic examination was performed. After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed. In case of macroscopic lesions, organ samples were taken and preserved in 10% buffered formalin. No microscopic examination was performed.
Statistics:
No data

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 10 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred during the observation period.
Clinical signs:
Signs of hypoactivity were observed at 2000 mg/kg bw in one female, 30 minutes after treatment and in two females after 1 and 2 hours. No clinical signs were noted at 10000 mg/kg bw.
Body weight:
The body weight gain of the animals was not affected by treatment with the test substance.
Gross pathology:
No abnormalities were observed at necropsy.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the oral LD50 of the test substance is =10000 mg/kg bw in rats. Therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the Globally Harmonised System of classification and labelling of chemicals (GHS). No signal word or hazard statement is required.
Executive summary:

In an acute oral toxicity study performed according to the OECD Guideline 401 and in compliance with GLP, a single dose of 2000 or 10000 mg/kg bw (in two fractions of 5000 mg/kg bw each) of the test substance was given by oral gavage to groups of Sprague Dawley rats (5/sex/dose). Animals were then observed for mortality, clinical signs and body weight changes for 14 days, and were all sacrificed for macroscopic examinations.

No death occurred at 2000 or 10000 mg/kg bw. Signs of hypoactivity were observed at 2000 mg/kg bw within two hours after treatment in two females only. No clinical signs were noted at 10000 mg/kg bw. The body weight gain of the animals was not affected by treatment with the test substance. No abnormalities were observed at necropsy.

Rat Oral LD50 =10000 mg/kg bw.

Under the test conditions, the oral LD50 of the test substance is =10000 mg/kg bw in rats. Therefore it is not classified according to the Regulation (EC) N° 1272-2008 and according to the Globally Harmonised System of classification and labelling of chemicals (GHS). No signal word or hazard statement is required.