Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
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:
1981
Report Date:
1981

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1981)
Deviations:
yes
Remarks:
(no constant volume was applied)
Qualifier:
according to
Guideline:
other: OECD Short-Term and Long-Term Toxicology Groups Final Report (December 1979)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries
- Weight at study initiation: 250±40 g
- Fasting period before study: 16 h
- Housing: individually in conventional design stainless steel, wire mesh bottom cages
- Diet: Purina Rodent Chow, ad libitum
- Water: fresh water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
not specified (under controlled laboratory conditions)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
250, 500, 1000, and 1600 mg/kg bw (based on the results of a screening test)
No. of animals per sex per dose:
5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: frequently on the first day of dosing and twice a day thereafter (at least 4 h apart)
- Frequency of weighing: 24 h, 7 and 14 days after dosing
- Necropsy of survivors performed: yes
Statistics:
The oral median lethal dose, 95% confidence interval, and approximate slope of the dose response curve were calculated by a computerised version of Finney's (1972) Probit Method.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
436 mg/kg bw
Based on:
test mat.
95% CL:
210 - 730
Remarks on result:
other: Deaths occurred in all dose groups in 1/5 females at 250 mg/kg bw, 3/5 females at 500 mg/kg bw, 5/5 females at 1000 mg/kg bw, and 5/5 females at 1600 mg/kg bw.
Sex:
male
Dose descriptor:
LD50
Effect level:
866 mg/kg bw
Based on:
test mat.
95% CL:
567 - 1 368
Remarks on result:
other: Deaths occurred in 1/5 males at 500 mg/kg bw, 3/5 males at 1000 mg/kg bw, and 5/5 males at 1600 mg/kg bw.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
653 mg/kg bw
Based on:
test mat.
95% CL:
447 - 892
Mortality:
Deaths occurred in all dose groups with 1/5 females at 250 mg/kg bw, 3/5 females and 1/5 males at 500 mg/kg bw, 5/5 females and 3/5 males at 1000 mg/kg bw and 5/5 males and females each at 1600 mg/kg bw. The females exhibited to be the more sensitive species. The deaths occurred within one and a half hours following dosage in all cases except three animals, which died several hours later.
Clinical signs:
Surviving animals appeared normal within 48 h. Generally, signs of toxicity exhibited by rats included extreme lethargy, ataxia, convulsions and coma.
Body weight:
Food consumption and body weight gains were slightly depressed during the first 24 h following treatment, but appeared normal during the remaining part of the study period.
Gross pathology:
Necropsy of animals that died during the study showed haemorrhagic condition of the gastrointestinal tract. However, terminal sacrifice of surviving animals did not reveal any compound related gross pathological alterations in the tissues and organs examined.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are met, Category 4 classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test item was investigated for acute oral toxicity in a study conducted similar to OECD 401, and in compliance with GLP. 5 Sprague Dawly rats per sex received single doses of of 250, 500, 1000, and 1600 mg/kg bw of the test material via gastrointestinal intubation. Deaths occurred in all dose groups with 1/5 females at 250 mg/kg bw, 3/5 females and 1/5 males at 500 mg/kg bw, 5/5 females and 3/5 males at 1000 mg/kg bw and 5/5 males and females each at 1600 mg/kg bw. Signs of toxicity exhibited by surviving rats included extreme lethargy, ataxia, convulsions and coma, but were resolved within 48 h. Food consumption and body weight gains were slightly depressed during the first 24 h following treatment, but appeared normal during the remaining part of the study period. Necropsy of animals that died during the study showed haemorrhagic condition of the gastrointestinal tract. However, terminal sacrifice of surviving animals did not reveal any compound related gross pathological alterations in the tissues and organs examined. Based on the outcome of the study, the LD50 value for males was calculated to be 866 mg/kg bw, whereas the LD50 value for females was determined to be 436 mg(kg bw. The combined LD50 value (male/female) was calculated to be 653 mg/kg bw.