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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:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Crl:CD BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Kingston, Stone Ridge, New York
- Age at study initiation: 55 days (males); 65 days (females)
- Weight at study initiation: 184-232 g (males); 187-217 g (females)
- Fasting period before study: overnight
- Housing: 1/cage in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina certified rodent chow 5002 (C)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: approximately one week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 74-74 degrees F (23-24 degrees C)
- Humidity (%): 41-46%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hr light/12 hr dark


IN-LIFE DATES: From: July 21, 1992 To: August 6, 1992

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: corn oil dispersion
- Amount of vehicle (if gavage): corn oil dispersion 10 mL/kg
- Justification for choice of vehicle: corn oil is a standard vehicle
- Lot/batch no. (if required): 80H0835
- Purity: no data


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg


DOSAGE PREPARATION (if unusual): dispersed in corn oil using a magnetic stirring bar


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: N/A
Doses:
50, 250, 500, 750, 1000, 1500 mg/kg
No. of animals per sex per dose:
60
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing: 0.5, 1, 2, and 4 hr after dosing and once daily for 14 days; Body weights were recorded Day 0 prior to dosing and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The LD50 95% confidence limits were calculated from the logarithm of the doses and the incidence of maortality using the Thompson moving average procedure (W.R. Thompson, "Use of Moving Averages and Interpolation to Estimate Median-Effective Dose", Bacteriol. Rev. 11, pp. 115-145, 1947). Slope estimates were obtained using the methods outlined by Weil (C.S. Weil, "Economical LD50 and Slope Determinations", Drug and Chemical Toxicology 6(6), pp. 595-603, 1983). All calculations were performed using the Statistical Analysis System on an IBM mainframe computer (SAS Institute Inc. SAS User's Guide: Basics, Version 5 Edition, Cary, NC:SAS Institute Inc., 1985)

Results and discussion

Preliminary study:
Not applicable
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 500 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
612 mg/kg bw
95% CL:
442 - 848
Sex:
male
Dose descriptor:
LD50
Effect level:
1 177 mg/kg bw
95% CL:
974 - 1 422
Mortality:
- Time of death: Males - 2 at 1000 mg/kg on day 1; 1 at 1500 mg/kg 1 hr post-dosing (day 0); 3 at 1500 mg/kg on day 1; 1 at 1500 mg/kg on day 2. Females - 2 at 500 mg/kg 2 hr post-dosing (day 0); 1 at 500 mg/kg 4 hr post-dosing (day 0); 1 at 500 mg/kg on day 1; 1 at 750 mg/kg 1 hr post-dosing (day 0); 1 at 750 mg/kg 2 hr post-dosing (day 0); 5 at 1500 mg/kg 1 hr post-dosing (day 0); 1 at 1500 mg/kg 2 hr post-dosing (day 0).
- Number of deaths at each dose: (number of deaths/number treated)
Dose (mg/kg) 50 250 500 750 1000 1500
Males --- 0/6 0/6 0/6 2/6 5/6
Females 0/6 0/6 4/6 2/6 --- 6/6
Clinical signs:
No clinical signs related to test substance were observed in the 250-mg/kg group for males and in the 50- and 250-mg/kg groups for the females. Clinical signs indicative of neurotoxicity (abnormal gait, tremors, and convulsions) were observed at dose levels of 500 mg/kg and greater in survivors as well as decedents. Surviving animals recovered from the neurotoxic effects by day 2 of the study. Other clinical signs related to the test substance observed in survivors as well as decedents included prostration, abnormal breathing patterns, scant or no feces and ptosis.
Body weight:
There were no apparent dose-related body weight effects in this study.
Gross pathology:
Necropsy of the decedents revealed numerous gastro-intestinal effects related to the test substance. Necropsy of the survivors revealed no gross changes related to the test substance.
Other findings:
- Potential target organs: gastro-intestinal tract
- Other observations: Statistically significant sex-related difference in mortality observed.

Any other information on results incl. tables

Since there was a statistically significant sex-related difference in mortality observed, the LD50 was calculated separately for males and females.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The acute oral LD50 in female rats is 612 mg/kg.
Executive summary:

The acute oral toxicity of the test material was assessed in Crl:CD BR rats. The test material was dispersed in corn oil and gavaged to five groups of male rats (6/group) at 250, 500, 750, 1000 or 1500 mg/kg and five groups of female rats (6/group) at 50, 250, 500, 750 and 1500 mg/kg. The corn oil dispersions were dosed at a constant volume of 10 ml/kg body weight. Mortality was observed in the 1000 and 1500 mg/kg dose groups in males and in the 500, 750 and 1500 mg/kg dose groups in females. No clinical signs related to test substance were observed in the 250 mg/kg group for males and in the 50 and 250 mg/kg groups in females. Clinical signs at dose levels of 500 mg/kg and greater in survivors as well as decedents. Surviving animals recovered from the neurotoxic effects by day 2 of the study. Other clincial signs related to the test substance observed in survivors as well as decedents included prostration, abnormal breathing patterns, scant or no feces and ptosis. There were no apparent dose-related body weight effects in this study. Necropsy of the decedents revealed numerous gastro-intestinal effects related to the test substanced. Necropsy of the survivors revealed no gross changes related to the test substance. the no observed effect level (NOEL) was 250 mg/kg.

Since there was a statistically significant sex-related difference in mortality observed, the LD50 in males rats was 1177 mg/kg with 95% confidence limits of 974 and 1422 mg/kg. The acute oral LD50 in female rats was 612 mg/kg with 95% confidence limits oof 442 and 848 mg/kg.