Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
7 days post-administration period
Qualifier:
equivalent or similar to
Guideline:
other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics" by the Staff of the Division of Pharmacology FDA, 1959
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Zucht Winkelmann, Paderborn, Germany
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: young adult
- Weight at study initiation: 125 - 150 g
- Fasting period before study: not specified
- Housing: single
- Diet: Lab standard diet (sniff/Intermast), ad libitum
- Water: ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 45 - 55
- Air changes (per hr): not specified
- 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: 500 mg/mL, pH 6.0
- Amount of vehicle. 1.0 - 1.59 mL/kg



Doses:
1.0, 1.13, 1.26, 1.42, or 1.59 mL/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing:
observations: after 20 min, 1 h, 24 h 48 h and 7 days after administration.
weighing: befor adminsitration and after the 7 days observation period.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
640 mg/kg bw
Based on:
test mat.
Mortality:
After 24 h, no mortality was observed in the 1.0 mL/kg dose group. In the 1.13 mL/kg dose group, 2 dead animals were observed. In the 1.26 mL/kg dose group, 4 dead animals were observed. In the 1.42 mL/kg dose group, 8 dead animals were observed. In the 1.59 mL/kg dose group all animals were found dead. No further animals died during the observation period.
Clinical signs:
Following clinical signs were reported: lack of aktivity, coordination disorders, reduced muscle tonus, reduced reflexes, piloerektion. The clinical signs were observed from 20 min up to 48 h after administration. Thereafter, the surviving animals acted normal.
Body weight:
Bodyweight development of the surviving animals was normal.
Gross pathology:
In the unscheduled died animals reddening of the gastric mucosa was observed. The other sacrificed animals did not show any pathological abnormalities.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral toxicity study in rats similar to OECD guideline 401, an oral LD50 of 640 mg/kg bw was determined.
Executive summary:

In an acute oral toxicity study similar to OECD guidline 401 in rats, the LD50 of the test item was determined. The test item was administered to young adult male annd female Wistar rats (5/sex/dose group) via single oral gavage. The test item was diluted in arachis oil (500 mg/mL). Following doses were administered: 1.0, 1.13, 1.26, 1.42, or 1.59 mL/kg. Body weight was measured before adminstration and at the end of the observation period (7 days). Clinical signs and mortality were recorded after 20 min, 1 h, 24 h 48 h and 7 days after adminstration. Prescheduled died and surviving animals were subjected to gross pathological investigations.

After 24 h, no mortality was observed in the 1.0 mL/kg dose group. In the 1.13 mL/kg dose group, 2 dead animals were observed. In the 1.26 mL/kg dose group, 4 dead animals were observed. In the 1.42 mL/kg dose group, 8 dead animals were observed. In the 1.59 mL/kg dose group all animals were found dead. No further animals died during the observation period. Following clinical signs were reported: lack of aktivity, coordination disorders, reduced muscle tonus, reduced reflexes, piloerektion. The clinical signs were observed from 20 min up to 48 h after administration. Thereafter, the surviving animals acted normal. Bodyweight development of the surviving animals was normal. In the unscheduled died animals reddening of the gastric mucosa was observed. The other sacrificed animals did not show any pathological abnormalities.

Based on the number of died animals, a LD50 of 640 mg/kg bw was determined.