Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31 October 1984 - 14 November 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1,3-dihydro-5-methoxy-2H-benzimidazole-2-thione
EC Number:
253-326-2
EC Name:
1,3-dihydro-5-methoxy-2H-benzimidazole-2-thione
Cas Number:
37052-78-1
Molecular formula:
C8H8N2OS
IUPAC Name:
5-methoxy-1,3-dihydro-2H-benzimidazole-2-thione
Specific details on test material used for the study:
Batch: 13M 2163
Assay: 98,8%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
On arrival at the laboratory and before assignment to this study, the rats were subjected to a visual inspection. Any animal showing signs of disability was excluded. The animals were acclimatised to laboratory conditions for at least 3 days.
The rats were kept 2 in a cage in transparent Macrolon® cages, measuring approximately 40x20 cm.
The air was changed about 15 times per hour via a centrally placed air intake and two peripheral ventilators. Target values for temperature and humidity were 18-22 degrees C and 40-70%, respectively. Recorded values were within the stipulated limits.

The animal rooms were illuminated by artificial light from fluorescent tubes on a 12-hour light/dark cycle.

The animals were fasted overnight (approximately 16 hours) before dosing and for approximately 3 hours after dosing, but otherwise they had free access to feed. Food consumption during the study was not measured. The animals had free access to municipal tap water for human consumption throughout the study.
The feed is analysed regularly for nutrients and both feed and water regularly for chemical and microbial contaminants, according to current written standard operation procedures.

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
250, 500 and 750 mg/kg body weight
No. of animals per sex per dose:
The study included 3 groups of animals, with 6 males in each.
Control animals:
no
Details on study design:
All animals were weighed immediately before dosing. Surviving animals were weighed on days 1, 2, 3, 4, 7 and 14.
The animals were observed and clinical signs and mortality recorded at least once during the intervals 0-1,1-3, 3-6 and 6-24 hours and then daily up to 14 days after dosing.

Results and discussion

Preliminary study:
. In the dose finding phase the results showed that it was not relevant to include a dose higher than 750 mg/kg in the main study.
Effect levels
Key result
Sex:
male
Dose descriptor:
approximate LD50
Effect level:
> 750 - <= 1 000 mg/kg bw
Mortality:
No deaths occurred at the dose levels 250 and 500 mg/kg. 2 of 6 animals died on day 2 at the dose level 750 mg/kg
Body weight:
The animals in the 2 lowest dose groups increased as expected in body weight, but the mean body weight of the animals in the highest dose group decreased from treatment up to day 2. The mean body weight subsequently increased, but was still lower than those of the other dose groups at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Evident toxicity in rats at a dose of 750 - 1,000 mg/kg