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Description of key information

Acute toxicity: oral: LD50 > 2000 mg/kg bw (OECD 401 in rats; GLP, K, Rel.1)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From August 14 to 28, 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(environmental conditions of animal room not reported)
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Storage condition of test material: Stored at room temperature, away from the light and heat (tox specific)
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: IFFA-CREDO, 69210 L'Arbresle, France
- Age at study initiation: 6 weeks
- Weight at study initiation: Males: 182-203 g; females: 161-188 g.
- Fasting period before study: Animals were fasted overnight prior to test material administration.
- Housing: Animals were housed in groups of 5 by sex in polypropylene cages
- Diet: Complete pelleted rat maintenance diet UAR A04-10 (91360- Epinay sur Orge, France)
- Acclimation period: 5 days

IN-LIFE DATES: From: August 14, 1997 To: August 28, 1997.
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 5 mL/kg bw
- Lot/batch no. (if required): Cooper batch F16539

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

DOSAGE PREPARATION (if unusual): Test material was suspended in 0.5 % carboxymethylcellulose (CMC). Preparation was kept up under magnetic stirring during the treatments.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
General appearance, behaviour and vegetative functions of the animals were observed at 1 h after the treatment and during the following 5 h daily for 14 days. Body weights were recorded just prior to the test material administration (on Day 1) and again on Days 4, 8 and 15.
- Necropsy of survivors performed: Yes; animals were sacrificed after barbituric anaesthesia and then autopsied for macroscopic examinations.
Statistics:
None
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed.
Mortality:
- No mortality was observed.
Clinical signs:
- No clinical signs were observed.
Body weight:
- Body weight gain was normal.
Gross pathology:
- No abnormality was noted at autopsy.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50 Combined > 2000 mg/kg bw. Not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw and not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the
range of Category 5 values (GHS criteria not met).
Executive summary:

In an acute oral toxicity study (limit test), performed according to OECD Guideline No. 401 and in compliance with GLP, a group of Sprague Dawley OFA rats (5/sex) were administered a single oral dose of test material suspended in 0.5 % carboxymethylcellulose at 2000 mg/kg bw under a constant volume of 5 mL/kg bw by gavage. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No mortality or clinical signs were observed. All animals showed normal body weight gains after the 14 day study period. No abnormalities were noted at autopsy.  

Oral LD50 Combined > 2000 mg/kg bw  

Under the test conditions, the test material is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw and is not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The key study is GLP-compliant and of high quality (Klimisch score = 1)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral

A key study was identified (EVIC, 1997). In this acute oral toxicity study, performed according to OECD Guideline No. 401 and in compliance with GLP, a group of Sprague Dawley OFA rats (5/sex) were administered a single oral dose of test material suspended in 0.5 % carboxymethylcellulose at 2000 mg/kg bw under a constant volume of 5 mL/kg bw by gavage. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. No mortality or clinical signs were observed. All animals showed normal body weight gains after the 14 day study period. No abnormalities were noted at autopsy.

Oral LD50 Combined > 2000 mg/kg bw.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Acute toxicity via Oral route:

Based on the available data, the substance is:

- not classified according to the Regulation (EC) No. 1272/2008 as the LD50 is greater than 2000 mg/kg bw

- not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

Acute toxicity via Dermal route:

No data was available.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw ≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

No data was available.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.

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