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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Justification for type of information:
data is from study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
equivalent or similar to
Guideline:
other: Federal Register Vol 50 no 188, Part II, 27 September 1985
Version / remarks:
section 798-1175-Acute oral toxicity
Principles of method if other than guideline:
Acute Oral toxicity test was carried out to study the effects of the given test chemical on rats.
GLP compliance:
yes
Remarks:
statement by study director and statement by QA
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
white powder
stored at ambient temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd, Margate, Kent, England
- Strain: pretest CFY, main test CD
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 100-149 g
- Fasting period before study: overnight and 4 hours after dosing
- Housing: in metal cages with wire mesh floors
- Diet: Labsure LAD 1 ad libitum
- Water: ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23 °C
- Humidity (%): average 57%
- Air changes (per hr): 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
VEHICLE: 1% methylcellulose
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
pre-test: 800, 1600 and 5000 mg/kg bw
main test: 500, 800 and 1260 mg/kg bw
No. of animals per sex per dose:
pre-test: 2/sex/dose
main test: 5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (pre-test 5 days)
- Frequency of observations: twice daily (and at regular intervals on day 1)
- Bodyweight: on day 1, 8 and 15
- Necropsy of survivors performed: no (only on animals that died)
- Other examinations performed: clinical signs daily
Statistics:
Probit analysis (Finney)

Results and discussion

Preliminary study:
All animals died at 1600 and 5000 mg/kg bw on day 1
At 800 mg/kg bw 1 male died on day 1
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
627 mg/kg bw
Based on:
test mat.
95% CL:
>= 425 - <= 783
Sex:
male
Dose descriptor:
LD50
Effect level:
578 mg/kg bw
Based on:
test mat.
95% CL:
>= 329 - <= 787
Sex:
female
Dose descriptor:
LD50
Effect level:
685 mg/kg bw
Based on:
test mat.
95% CL:
>= 437 - <= 983
Mortality:
males: 500 mg/kg bw 2/5 before day 4; 800 mg/kg bw 5/5 before day 3; 1260 mg/kg bw 4/5 on day 1
females: 500 mg/kg bw 0/5 before day 4; 800 mg/kg bw 4/5 on day 1; 1260 mg/kg bw 5/5 on day 1
Clinical signs:
pilo-erection, hunched posture, waddling, decreased respiratory rate and pallor of the extremities in all animals
Ptosis, prostrate and facial swelling were observed less frequently.
Body weight:
Body weight change was observed for survivors within normal ranges.
Gross pathology:
No abnormalities was observed.
Other findings:
not specified

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral toxicity dose (LD50) value was considered to be 627 mg/kg bw, with 95% confidence limit of 425-783 mg/kg bw in combined male and female rats; 578 mg/kg bw, with 95% confidence limit of 329-787 mg/kg bw in male rats and 685 mg/kg bw, with 95% confidence limit of 437-983 mg/kg bw in female rats.
Executive summary:

The acute oral toxicity study was conducted as per OECD Guideline 401 (Acute Oral Toxicity) and Federal Register Vol 50 no 188, Part II, 27 September 1985 by using the given test chemical in male and female Sprague-Dawley rats.

The given test chemical (Purity 100%) was dissolved in 1% methylcellulose and administered as 10 mL/kg bw via oral gavage route.

In pre-test: 2/sex/dose male and female Sprague-Dawley rats were treated with the given test chemical at the dose concentration of 800, 1600 and 5000 mg/kg bw. Animals were observed for mortality for 5 days. Necropsy was performed only on animals that died. All animals died at 1600 and 5000 mg/kg bw on day 1. At 800 mg/kg bw 1 male died on day 1.

In main test: 5/sex/dose male and female Sprague-Dawley rats were treated with the given test chemical at the dose concentration of 500, 800 and 1260 mg/kg bw.

Animals were observed for mortality daily twice (and at regular intervals on day 1). Body weight was observed on day 1, 8 and 15. Necropsy of survivors performed only on animals that died. Clinical signs were observed daily. LD50 value was calculated by the method of probit analysis (Finney).

Mortality was observed as - males: At 500 mg/kg bw 2/5 before day 4; At 800 mg/kg bw 5/5 before day 3; At 1260 mg/kg bw 4/5 on day 1. Females: At 500 mg/kg bw 0/5 before day 4; At 800 mg/kg bw 4/5 on day 1; At 1260 mg/kg bw 5/5 on day 1. Clinical signs like, piloerection, hunched posture, waddling, decreased respiratory rate and pallor of the extremities in all animals and Ptosis, prostrate and facial swelling were observed less frequently in treated animals. Body weight change was observed for survivors within normal ranges. No abnormalities were observed after necropsy.

Under the condition of the study, the acute oral toxicity dose (LD50) value was considered to be 627 mg/kg bw, with 95% confidence limit of 425-783 mg/kg bw in combined male and female rats; 578 mg/kg bw, with 95% confidence limit of 329-787 mg/kg bw in male rats and 685 mg/kg bw, with 95% confidence limit of 437-983 mg/kg bw in female rats.