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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
Study period:
December 22, 1994 - January 5, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

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:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hiltop Lab Animals, Scottdale
- Weight at study initiation: 197-216 g (males), 201-215 g (females)
- Fasting period before study: approximately 21 hours
- Housing: individually (suspended stainless steel caging with mesh floors)
- Diet: Purina Rodent Chow (Feed was replaced approximately 3 hours after dosing.)
- Water: Tap water (ad libitum)
- Acclimation period: 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6 – 22.2
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 4.71 mL/kg

DOSAGE PREPARATION: Individual doses were calculated based on the initial bodyweights, taking into account the specific gravity of the test substance.

Doses:
5000 mg/kg bw/day
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual weights of the animals were recorded just prior to test substance administration (initial) and again on days 7 and 14 (termination). The animals were observed for signs of gross toxicity, behavioral changes and mortality at 0.5, 1, 3 and 20.75 hours post-dosing and at least once daily thereafter for 14 days.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
A preliminary rangefinding screen was conducted at dose levels of 100, 300, 1000, 3000 and 5000 mg/kg bw. The test substance was administered by oral gavage to one male and one female per dose level. The test substance was administered to each animal and the animals were observed daily for 7 days. Based on the range finding screen, a dose level of 5000 mg/kg bw was selected for the limit test.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 5000 mg/kg bw; Number of deaths: 0 of 10
Female: 5000 mg/kg bw; Number of deaths: 0 of 10
Clinical signs:
Within thirty minutes of administration, all animals developed clinical signs including hunched posture, piloerection, irregular respiration, hypoactivity, diarrhea and ano-genital staining.

Body weight:
There was no remarkable body weight change.
Gross pathology:
There were no test article related findings noted.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of testing, the single dose Acute Oral Toxicity LD50 of the test substance is greater than 5000 mg/kg of bodyweight when administered as received.
Executive summary:

An Acute Oral Toxicity test according to OECD Guideline 401 was conducted with rats to determine the potential for the test item to produce toxicity via the oral route. A preliminary rangefinding screen was conducted at dose levels of 100, 300, 1,000, 3000 and 5000 milligrams of the test substance per kilogram of bodyweight. The test substance was administered by oral gavage to one male and one female per dose level. Based on the results of the rangefinding screen, 5000 mg/kg bw was selected as the dose level for the full test.

Ten (five males and five females) healthy rats were selected for the full test. Each animal received 5000 mg/kg bw of the test substance by oral intubation using a stainless steel ball-tipped gavage needle attached to an appropriate syringe.

The animals were observed for signs of gross toxicity and mortality at least once daily for 1 4 days. Bodyweights were recorded just prior to administration and again on days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.

All animals survived and gained weight. Following administration, all rats developed clinical signs including hunched posture, piloerection, irregular respiration, hypoactivity, diarrhea and ano-genital staining. All animals recovered by day 4 and appeared active and healthy for the remainder of the 14-dav observation period. Gross necropsy findings at terminal sacrifice were generally unremarkable.

Based on the results of testing, the single dose Acute Oral Toxicity LD50 of the test substance is greater than 5000 mg/kg of bodyweight when administered as received.