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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1983-10-03 to 1983-10-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Although signs of toxicity and effects in organs for individual animals dosed at 1000 mg/kg were missing from the report, the UK c.a. considers that overall an adequate description of the toxic effects was given. Experimental test were run under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Annex V
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): 5601-22-20, Order # J-174
- Physical state: Light yellow liquid
- Lot/bach No.: Order # J-174
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration
- Other: base factor: Specific gravity = 0.952 g/ml; 1 quart supplied on September 26, 1983; the purity of the test article is the responsibility of the sponsor

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Blue Spruce Farms, Altamont, New York
- Weight at study initiation: 180-360 g (weight variation in animals or between groups did not exceed +/- 20%)
- Fasting period before study: 18 hours
- Housing: Rats housed in groups, according to sex, or individually in stainless steel 1/2" wire mesh cages.
- Diet (e.g. ad libitum): Wayne Lab BloxR, ad libitum
- Water (e.g. ad libitum): Fresh tap water, fit for human consumption, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: None (Liquid substance used undiluted)
Doses:
800, 1000, 1600, and 2000 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose
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 approximately 1, 2, 4 and 24 hours after dosing and twice daily for 14 days for pharmacotoxic, CNS effects and mortality. On days 7 and 14, body weights were recorded.
- Necropsy of survivors performed: yes
Statistics:
According to the method of Litchfield and Wilcoxon (1949) JPET 96:99-114

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 364 mg/kg bw
95% CL:
1 110 - 1 675
Sex:
male
Dose descriptor:
LD50
Effect level:
1 693 mg/kg bw
95% CL:
1 433 - 1 999
Sex:
female
Dose descriptor:
LD50
Effect level:
1 007 mg/kg bw
95% CL:
830 - 1 222
Mortality:
Mortality by Sex and Dose:
Male: 800 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Male: 1600 mg/kg bw; Number of animals: 5; Number of deaths: 2
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 4

Female: 800 mg/kg bw; Number of animals: 5; Number of deaths: 1
Female: 1000 mg/kg bw; Number of animals: 5; Number of deaths: 2
Female: 1600 mg/kg bw; Number of animals: 5; Number of deaths: 5
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 4

One out of ten died at the 800 mg/kg level, two out of ten died at the 1000 mg/kg level, seven out of ten died at 1600 mg/kg and eight out of ten died at 2000 mg/kg.
Clinical signs:
other: Signs of toxicity related to dose levels: At 1600 mg/kg and 2000 mg/kg, all deaths occurred within 24 hours of dosing apart from one top dose female which died between 72 and 96 hours post exposure. At these doses, toxic signs were primarily decreased act
Gross pathology:
Effects on organs:
Necropsy of decedents dosed at 1600 and 2000 mg/kg generally showed distended stomachs and intestines with stomach haemorrhages. Discoloured or haemorrhagic intestines were noted in 2/7 and 1/8 decedents at 1600 and 2000 mg/kg respectively and two top dose decedents showed darkened adrenals. Effects in organs specifically for the 1000 mg/kg dose group were missing from the report. No macroscopic effects on organs were observed in surviving animals.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The calculated oral LD50 for male and female rats was determined to be 1364 mg/kg (1110-1675 mg/kg). The calculated oral LD50 for male rats was determined to be 1693 mg/kg (1433-1999 mg/kg). The calculated oral LD50 for female rats was determined to be 1007 mg/kg (830-1222 mg/kg). The substance is considered to be classified as acute oral toxicant category 4 according to the criteria laid down in the CLP Regulation (EC) 1272/2008.