Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was not conducted in compliance with GLP regulations but was well documented and scientifically acceptable. The study was conducted in general compliance with OECD 401 (1987) with the exception that 3 rats/sex were used rather than 5 rats of one sex. The results are sifficiently described to make conclusions about the rat acute oral LD50 of the test article.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
The study used 3 rats/sex/group rather than 5 rats of one sex/group.
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): Z-Acetate
- Substance type: Mono-constituent
- Physical state: Liquid
- Analytical purity: Not reported
- Lot/batch No.: Batch 0008

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL Biological Research Laboratories Ltd.
- Age at study initiation: Males: 10 weeks, Females: 12 weeks
- Weight at study initiation: Males: 236-268 g, Females: 189-192 g
- Fasting period before study: 12-18 hours
- Housing: Individually
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: One week under laboratory conditions after veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: 14 August 1989 To: 04 September 1989

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): Dose volume was 10 mL/kg at 2000 mg/kg test article

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The rats were observed at 1, 2, 3, and 5 hours postdose and then once daily for 14 days. Animals were weighed on Days 1, 8, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gross pathology

Results and discussion

Preliminary study:
No data.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
All animals survived through the observation period.
Clinical signs:
Sedated behavior (2/6 animals), ruffled fur (2/6), dyspnea (1/6) and/or hunched posture (1/6) were noted in animals from 2 hours post-dose to Day 2. On Day 3, ruffled fur was noted in one animal and all other findings had resolved. All animals were normal on Day 4.
Body weight:
Body weights were normal throughout the study.
Gross pathology:
No abnormal gross findings were identified upon necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, the oral LD50 of the test article is greater than 2000 mg/kg.
Executive summary:
The acute oral toxicity of the test article (liquid, batch 0008) was evaluated in male and female Wistar rats. The study design was based on OECD 401 (1987) and EEC Guidelines B.1 (1984) with the exception that 3 rats/sex were used rather than 5 rats of one sex. The test article was diluted in bi-distilled water prior to administration. Rats (3/sex) received 2000 mg/kg test article via oral gavage. The rats were observed at 1, 2, 3, and 5 hours postdose and then once daily for 14 days. Body weights were recorded pretest, weekly, and at termination. All animals were examined for gross pathology. All animals survived. Sedated behavior (2/6 animals), ruffled fur (2/6), dyspnea (1/6) and/or hunched posture (1/6) were noted in animals from 2 hours post-dose to Day 2. On Day 3, ruffled fur was noted in one animal and all other findings had resolved. All animals were normal on Day 4. Body weights and gross pathology observations were normal. Based on the results of this study, the oral LD50 of the test article is greater than 2000 mg/kg.