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Description of key information

LD50 oral (rat): 1000 mg/kg bw (males)

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:
15 Feb 1989 to 13 Apr 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Substance type: organic
- Physical state: liquid
- Stability under test conditions: stable
- Storage condition of test material: room temperature
- Physical state: Liquid
- Lot/batch No.: 05774HP8
Species:
rat
Strain:
other: Tif: RAI f (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland
- Age at study initiation: 7 to 8 weeks
- Weight at study initiation: 174 to 215 g
- Fasting period before study: Prior to treatment fasted overnight.
- Housing: The rats, segregated by sex, were group-housed (5 animals per cage) in Macrolon cages type 4, with standardized soft wood bedding (Societe Parisienne des Sciures, Pantin).
- Diet: Rat chow (NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 55 +/- 10 %.
- Air changes (per hr): approximately 15 air changes/h
- Photoperiod (hrs dark / hrs light): 12 hour/day light cycle
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

Doses:
200 mg/kg (females), 500 mg/kg (males and females), and 2000 mg/kg (males)
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: observations daily; weighing immediately before administration and on days 7, 14, and at death
- Necropsy of survivors performed: yes; Spontaneously dying animals were submitted to a gross necropsy as soon as possible,- survivors at the
end of the observation period.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
Statistics:
The LD50 values were computed by the logit model (J. Berkson, 1944)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 1 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1 085 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 265 mg/kg bw
Based on:
test mat.
Mortality:
Males:
500 mg/kg: 2/5
2000 mg/kg: 3/5

Females:
200 mg/kg: 0/5
500 mg/kg: 1/5
Clinical signs:
Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests. Respiratory sounds were noted in animals dosed with 200 and 500 mg/kg. Slightly to moderately reduced locomotor activity was observed in the animals of the 500 and 2000 mg/kg dose group. A distended abdomen was recorded in single animals of all dose groups. Diarrhea showed one male given 500 and 2000 mg/kg, respectively.
The surviving animals of the 500 and 2000 mg/kg bw dose group recovered within 6 to 10 days.
In one female dosed with 200 mg/kg dyspnea, respiratory sounds, and a distended abdomen persisted until the day of sacrifice. One male of the 500 mg/kg dose group had to be euthanasized on day 8 because of increasing distended abdomen and moderate dyspnea.
Body weight:
normal body weight gain
Gross pathology:
At autopsy, a hemorrhagic thymus was found in one female of the 500 mg/kg dose group. A dilated stomach and a small intestine was found in two males of the same dose group and in three given 2000 mg/kg. The latter three showed also a dilated caecum.
Interpretation of results:
Category 4 based on GHS criteria
Executive summary:

Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 values were determined for the test article:

LD50 in male rats: 1000 mg/kg body weight

LD50 in female rats: 1085 mg/kg body weight

LD50 in rats of both sexes: 1265 mg/kg body -weight (lower 95% confidence limit 505 mg/kg)

Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests. Respiratory sounds were noted in animals dosed with 200 and 500 mg/kg. Slightly to moderately reduced locomotor activity was observed in the animals of the 500 and 2000 mg/kg dose group. A distended abdomen was recorded in single animals of all dose groups. Diarrhea showed one male given 500 and 2000 mg/kg, respectively. The surviving animals of the 500 and 2000 mg/kg bw dose group recovered within 6 to 10 days. At autopsy, a hemorrhagic thymus was found in one female of the 500 mg/kg dose group. A dilated stomach and a small intestine was found in two males of the same dose group and in three given 2000 mg/kg. The latter three showed also a dilated caecum.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 000 mg/kg bw

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 oral toxicity:

In a GLP-compliant oral toxicity study performed with rats, groups of male and female animals were treated with the test article by gavage. Dose levels were 200 and 500 mg/kg bw (females) and 500 and 2000 mg/kg bw (males) followed by a 14 day post-treatment observation period. The following LD50 values were determined in this study:

LD50 in male rats: 1000 mg/kg body weight

LD50 in female rats: 1085 mg/kg body weight

LD50 in rats of both sexes: 1265 mg/kg body-weight (lower 95% confidence limit 505 mg/kg)

The following symptoms were observed: Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests. Respiratory sounds were noted in animals dosed with 200 and 500 mg/kg. Slightly to moderately reduced locomotor activity was observed in the animals of the 500 and 2000 mg/kg dose group. A distended abdomen was recorded in single animals of all dose groups. Diarrhea showed one male given 500 and 2000 mg/kg, respectively. The surviving animals of the 500 and 2000 mg/kg bw dose group recovered within 6 to 10 days. At autopsy, a hemorrhagic thymus was found in one female of the 500 mg/kg dose group. A dilated stomach and a small intestine was found in two males of the same dose group and in three given 2000 mg/kg. The latter three showed also a dilated caecum (Ciba-Geigy, 1989).

Justification for classification or non-classification

Based on the available data, the substance has to be classified as Acute Tox. 4 H302: Harmful if swallowed in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

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