Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

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:
other: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labeling and/or risk assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct.
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Purity: 86%

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 9-11 weeks
- Weight at study initiation: 267.8-331.2 grams
- Fasting period before study: 16-18 hours
- Housing:All animals were housed singly in stainless steel, wire-mesh cages suspended above cage boards.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26
- Humidity (%): 30-70
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
175, 550, 1750, 5000 mg/kg
No. of animals per sex per dose:
175 mg/kg (1 male rat), 550 mg/kg (2 male rats), 1750 mg/kg (4 male rats), 5000 mg/kg (3 male rats)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: The rat were observed for clinical signs at the beginning of fasting, just before dosing (test day 0), once during the first 30 minutes after dosing and 2 more times on the day of dosing, and once each day thereafter.
-Frequency of weighing: The rats were weighed on test days –1, 0, 7, and 14.
- Necropsy of survivors performed: yes
Statistics:
A software package (A0T425StatPgm)a was used to determine the dose progression and the LD50.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
1 750 mg/kg bw
95% CL:
1 239 - 4 450
Mortality:
Death occurred in one rat dosed at 1750 mg/kg and in all 3 rats dosed at 5000 mg/kg.
Clinical signs:
Lethargy was observed on the day of dosing in the rat dosed at 175 mg/kg. The 2 rats dosed at 550 mg/kg exhibited wet fur up to the day after dosing. Three surviving rats dosed at 1750 mg/kg exhibited wet fur and stained fur/skin up to the day after dosing. One of these rats also exhibited low posture on the day of dosing. The remaining rat dosed at 1750 mg/kg exhibited lethargy, stained fur/skin, and wet fur on the day of dosing and was found dead on the day after dosing. Lethargy was observed on the day of dosing in one of the rats dosed at 5000 mg/kg. This rat was found dead on the day of dosing. Another rat dosed at 5000 mg/kg exhibited lung noise, lethargy, decreased muscle tone, stained fur/skin, and wet fur on the day of dosing and was found dead on the day after dosing. The remaining rat dosed at 5000 mg/kg exhibited lethargy and was found dead on the day of dosing.
Body weight:
No body weight loss occurred in the surviving rats after dosing.
Gross pathology:
Gross findings were present in 1 rat dosed at 1750 mg/kg and 3 rats dosed at 5000 mg/kg. These included skin stain, lungs expanded, eye discoloration, and/or stomach discoloration. No other gross findings were observed.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: other: Directive 67/548/EEC
Conclusions:
The oral LD50 for the test substance was 1750 mg/kg in male rats.
This study and the conclusions which are drawn from it fulfill the quality criteria (validity, reliability, repeatability).
Executive summary:

A single dose of the test substance was administered by oral gavage to 1 fasted male rat at a dose of 175 mg/kg, to 2 fasted male rats at a dose of 550 mg/kg, to 4 fasted male rats at a dose of 1750 mg/kg, and to 3 fasted male rats at a dose of 5000 mg/kg. The rats were dosed one at a time at a minimum of 48-hour intervals. The rats were observed for mortality, body weight effects, and clinical signs for up to 14 days after dosing. All rats were necropsied to detect grossly observable evidence of organ or tissue damage. One of the rats dosed at 1750 mg/kg was found dead on the day after dosing, and the 3 rats dosed at 5000 mg/kg were found dead on the day of dosing or the day after dosing. Clinical signs of toxicity were observed in all rats up to the day after dosing and included lethargy, wet fur, stained fur/skin, lung noise, decreased muscle tone, and/or low posture. No body weight losses occurred in the surviving rats. Gross findings were present in 1 rat dosed at 1750 mg/kg and 3 rats dosed at 5000 mg/kg. These included skin stain, lungs expanded, eye discoloration, and/or stomach discoloration. No other gross findings were observed. Under the conditions of this study, the oral LD50 for the test substance was 1750 mg/kg for male rats. The 95% profile likelihood confidence interval is 1239 to 4450 mg/kg.