Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1992/11/06 to 1993/02/18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Old study, the report is not as detailed as would now be expected (for example test material details). Minor deficiencies such as bodyweight recordings missed.

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)
Deviations:
not specified
GLP compliance:
yes
Test type:
other: LD50
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Limited
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 106-207g
- Fasting period before study: overnight
- Housing: polypropylene cages with mesh floors
- Diet (e.g. ad libitum): ad libitum except for overnight before dosing and 4 hour after dosing
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 50
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To: 1992/12/02 to 1993/02/18

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2000 mg/kg (limit test)
1000, 1400, 1800, 2200 (LD50)
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to dosing, 7 days and at death or end of study (14 days)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology,
Statistics:
Finney (1971) and Berson (1953)

Results and discussion

Preliminary study:
4 out of 5 male rats and 3 out of 5 female rats died at 2000 mg/kg
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 387 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
1 529 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 372 mg/kg bw
Based on:
test mat.
Mortality:
Dose level (mg/kg)
1000 (0/5 male and 4/5 female)
1400 (3/5 male and 0/5 female)
1800 (5/5 male and 1/5 female)
2200 (5/5 male and 5/5 female)
Clinical signs:
noted 1 min to 3 days after dosing: piloerection, soiled coat, watery ocular discharge, subdued behaviour, prostration, tremors, hunched appearance, low body temperature, laboured breathing, increased salivation and activity, ataxia and pale extremities
Body weight:
body weight gains were described as acceptable
Gross pathology:
In premature decedents only: these were confined to the mucosal surfaces of the stomach which were noted to be dark red in appearance. In additional and area of ulceration of the mucosal surface was observed in one animal.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The estimated LD50 is 1372 mg/kg bw for males and females
Executive summary:

Following a single orally administered dose of Frit (10 mL/kg in maize oil) at a dose level of 2000 mg/kg bw, 4 of the 5 male Sprague Dawley rats and 3 of the 5 female Sprague Dawley rats died. A further 4 dose levels of 1000, 1400, 1800 and 2200 mg/kg bw were selected to determine the LD50 value. In the LD50 test, deaths occurred 4h to 4 days after dosing.

Clinical signs, noted 1 min to 3 days after dosing, included piloerection, soiled coat, watery ocular discharge, subdued behaviour, prostration, tremors, hunched appearance, low body temperature, laboured breathing, increased salivation and activity, ataxia and pale extremities.

Necropsy findings, in premature decedents only, were confined to the mucosal surfaces of the stomach which were noted to be dark red in appearance. In additional and area of ulceration of the mucosal surface was observed in one animal.

The Median Oral Lethal Doses (LD50s) and 95% confidence intervals of Frit for male and female rats are estimated to be:

Males              1387 mg/kg

Females           1529 mg/kg

Males and Females       1372 (937 -1721) mg/kg

Note - no confidence intervals can be given for the male and female LD50 values due to the spread of the fractional mortality data