Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ziram
- Lot no.: 8331 AA
- Purity: 98.5% purity

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 142-158g

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
- Concentration in vehicle: 1% w/v
- Amount of vehicle: 20.0 mL/kg
Doses:
250, 400, 640 mg/kg
No. of animals per sex per dose:
5
Control animals:
no

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
267 mg/kg bw
95% CL:
113 - 393
Sex:
male
Dose descriptor:
LD50
Effect level:
381 mg/kg bw
95% CL:
227 - 594
Sex:
male/female
Dose descriptor:
LD50
Effect level:
320 mg/kg bw
95% CL:
176 - 422
Mortality:
There were deaths amongst males and females dosed at all dose levels. Deaths occurred from Day 2 to Day 3.
at 250 mg/kg: 1m/2f
at 400 mg/kg: 3m/4f
at 640 mg/kg: 4m/5f
Clinical signs:
Pilo-erection was observed in all rats within five minutes of dosing. This was accompanied by abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, ptosis, pallor of the extremities and diarrhoea in all rats at later intervals on Day 1.
Recovery, as judged by external appearance and behaviour, was complete by Day 3 or Day 5.
Body weight:
Slightly low bodyweight gains were recorded for one male and one female dosed at 250 mg/kg and one male dosed at 640 mg/kg on Day 8. All other rat achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Autopsy revealed no abnormalities.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the lower LD50 of 267 mg/kg bw in female rats, ziram is classified as Acute Tox 3, H301: Toxic if swallowed