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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-08-01 to 1996-08-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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:
February 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
29 December 1992
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
HsdCpb: WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, 33178 Borchen, Germany
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: about 6 to 9 weeks
- Weight at study initiation: 152 - 202 g (mean: 177 g)
- Fasting period before study: ca. 17 h before and 4 h after treatment
- Housing: single, Makrolon cages type III
- Diet: ad libitum, besides fasting period
- Water: ad libitum, besides fasting period, tap water
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 25
- Humidity (%): 41 - 77
- Air changes (per hr): not detailed, but room air-conditioned
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 08.08.1996 - 29.08.1996

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
1.697 mL/kg bw for 2000 mg/kg bw
0.849 mL/kg bw for 2000 mg/kg bw
Doses:
1000 and 2000 mg/kg bw
No. of animals per sex per dose:
2000 mg/kg bw: 5 per sex
1000 mg/kg bw: 5 male
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: observation: daily; body weight: on days 2, 4, 6, 8,11, 13, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
For body weights the group mean value and the difference to the first value, expressed as percentage, were calculated for each measurement.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 1 000 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 3 Deaths occured up to day 3 after treatment.
Male: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
1000 mg/kg: locomotor disturbance started between 15 to 60 minutes after treatment and lasted on day 1.
2000 mg/kg: Symptoms of intoxication were first seen 1 to 15 minutes after treatment. They lasted up to day 3 and consisted of locomtor disturbance, dyspnea, retention of feces, blood crusted snout, salivation, and abdominal position.
Body weight:
Body weight development was impaired on day 2 for females and on day 2 and 4 for males treated with 2000 mg/kg bw. Afterwards bodyweight gain was observed.
Males treated with 1000 mg/kg bw showed body weight gain on all days.
Gross pathology:
The rats that died or were sacrificed at the end of the observation period did not show any abnormalities in the macroscopic examination.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
For both sexes the combined LD50 was therefore determined to be >1000 to < 2000 mg/kg bw.
Executive summary:

An in vivo oral toxicity study according to OECD 401 using the test substance was conducted in rats. Each 5 male and female animals were treated with 2000 mg/kg bw test substance per gavage and observed for 15 days. Furthermore, 5 males were treated with 1000 mg/kg bw test substance. In animals treated with 2000 mg/kg bw symptoms of intoxication were first seen 1 to 15 minutes after treatment. They lasted up to day 3 and consisted of locomotor disturbance, dyspnea, retention of feces, blood crusted snout, salivation, and abdominal position. After treatment with 1000 mg/kg bw locomotor disturbance developed after 15-60 minutes and lasted up to one day. Three male rats from the high dose group died up to day 3 of the study. Body weight development was impaired on day 2 for females and on day 2 and 4 for males treated with 2000 mg/kg bw. Afterwards bodyweight gain was observed. Males treated with 1000 mg/kg bw showed body weight gain on all days.No abnormalities were detected during gross pathological examinations. Based on the observed mortality the LD50 for male rats was determined to be below 2000 mg/kg bw but greater than 1000 mg/kg bw. For females the observed LD 50 was greater than 2000 mg/kg bw. For both sexes the combined LD50 was therefore determined to be >1000 to < 2000 mg/kg bw.