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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:
1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar 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 material form:
solid
Specific details on test material used for the study:
Purity : 73.1%
PROXEL Press Paste
Reference ADH374793, Bx973

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% aqueous polysorbate 80
Doses:
0, 100, 300, 500 and 900 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
670 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
490 mg/kg bw
Based on:
act. ingr.
Mortality:
There were no deaths in animals dosed with 100 or 300 mg/kg. One female dosed with 500 mg/kg was killed in extremis on Day 2. All the males and three females dosed with 900 mg/kg died or were killed in extremis on Days 1 or 2.
Clinical signs:
There were no signs of toxicity at any time in the animals dosed with 100 mg/kg. Signs of slight toxicity in those dosed with 300 mg/kg were piloerection and upward curvature of the spine, neither of which persisted after Day 3. Surviving animals dosed with 500 mg/kg also showed signs of slight toxicity until Day 3. These were of a slightly higher incidence than those seen following dosing with 300 mg/kg, and included dehydration, piloerection and upward curvature of the spine. Signs of marked toxicity were observed in the animals dosed with 900 mg/kg. The most common abnormalities were upward curvature of the spine, piloerection, sides pinched-in, dehydration, hypothermia and decreased activity. Two animals appeared cyanosed prior to death. The two surviving females had recovered by days 6 or 7.
Body weight:
The overall weight gain, throughout the study, was similar at all dose-levels.
Gross pathology:
There were no macroscopic abnormalities in any animal at necropsy.

Any other information on results incl. tables

The acute oral median lethal dose value was 670 mg/kg (approximate 95% confidence limits 500, 900) to male rats and 784 mg/kg (lower 95% confidence limit 475) to female rats.

Applicant's summary and conclusion

Conclusions:
Materials and methods
Groups of five male and five female rats were given a single oral dose of 100, 300, 500 or 900 mg/kg of PROXEL press paste, as preparations in 5% (w/v) aqueous polysorbate 80. The animals were weighed and observed for fourteen days after dosing. PROXEL press paste (wet) is a 73.1% BIT technical grade material.
The methodology employed was equivalent to those described in guidelines OECD401, EC B.1.

Results and discussion There were no deaths and no signs of toxicity at 100 mg/kg and no deaths but signs of slight toxicity at 300 mg/kg. One female dosed with 500 mg/kg was killed in extremis and there were signs of slight toxicity in the survivors. Following dosing with 900 mg/kg there were signs of marked toxicity and all the males and three females died or were killed in extremis on Days 1 or 2. There were no macroscopic abnormalities in any animal at necropsy.
The acute oral median lethal dose value was 670 mg/kg (approximate 95% confidence limits 500, 900) to male rats and 784 mg/kg (lower 95% confidence limit 475) to female rats.
Executive summary:

A study was conducted to determine the acute oral toxicity of the substance according to a method similar to OECD Guideline 401. Groups of five male and five female rats were administered a single oral dose of 0, 100, 300, 500 or 900 mg/kg bw of the substance in a 0.5% (w/v) aqueous polysorbate 80 suspension. The animals were weighed and observed for fourteen days after dosing. There was no mortality at 100 and 300 mg/kg. One female at 500 mg/kg bw was sacrificed in extremis. At 900 mg/kg bw there were signs of marked toxicity and all the males and three females died or were sacrificed in extremis on Day 1 or 2. There were no macroscopic abnormalities in any animal at necropsy. Under the study conditions, the acute oral LD50 of the substance was determined to be 670 mg/kg bw (490 mg a.i./kg bw) in rats (Leah, 1988).