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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:
1990
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): P5524
- Substance type: Powder
- Physical state: white powder
- Analytical purity: 102%
- Purity test date: 4. 1. 1990
- Lot/batch No.: 861201
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Bantin & Kingman ltd., Grimston, Aldborough, Hull, U.K.
- Age at study initiation: five to eight weeks
- Weight at study initiation: males weighed 120 - 144g, and the females 126 - 159g
- Fasting period before study: overnight fast immediately before dosing and for approximately two hours after dosing
- Housing: The animals were housed in groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 24°C, On one occasion the temperature was below the lower limit specified in the protocol (19°C)
- Humidity (%): 40 - 56%
- Air changes (per hr): approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1, 2, and 4 g/L
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: water soluble
- Purity: distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg with 4 g/L

DOSAGE PREPARATION (if unusual): For the purpose of this study the test material was freshly prepared, as required, at the appropriate concentration as a solution in distilled water.
Doses:
main study: 10, 20 and 40 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: day of treatment (day 0), days 7 and 14, or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy
Statistics:
Using the mortality data obtained the acute oral median lethal dose (LD50) and 95% confidence limits of the test material were calculated using the
method of Thompson W.R., Bact. Reviews, 11, 115-145 (1947). The LD50 and 95% confidence limits were calculated for males and females separately.
Clinical observations, bodyweight and necropsy data were examined for any adverse effects resulting from treatment.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
24 mg/kg bw
Based on:
test mat.
95% CL:
>= 19 - <= 32
Sex:
male
Dose descriptor:
LD50
Effect level:
24 mg/kg bw
Based on:
test mat.
95% CL:
14 - 39
Sex:
female
Dose descriptor:
LD50
Effect level:
25 mg/kg bw
Based on:
test mat.
95% CL:
19 - 32
Clinical signs:
All animals treated with 10 mg/kg appeared normal throughout the study.

Common signs of toxicity noted in dose groups 20 and 40 mg/kg were hunched posture, lethargy, pilo-erection, ptosis, ataxia and loss of righting reflex. Additional signs of toxicity noted in the 40 mg/kg dose group were decreased respiratory rate and isolated incidents of body tremors, red/brown stains around the snout, dehydration and pallor of the extremities. Surviving animals in dose groups 20 and 40 mg/kg appeared normal four days after dosing.
Body weight:
Surviving animals showed expected gain in bodyweight during the study.
Gross pathology:
Abnormalities noted at necropsy of animals that died or were killed in extremis during the study were haemorrhagic or abnormally red lungs,
dark liver, dark kidneys, haemorrhage of the glandular gastric epithelium and haemorrhage of the small and large intestines. The male treated with 20 mg/kg that was killed in extremis also showed an enlarged and blood filled bladder at necropsy.

No abnormalities were noted at necropsy of animals killed at the end of the study.

Applicant's summary and conclusion

Executive summary:

The acute oral toxicity test (Coles 1990) was performed according to OECD 401 and EEC method B.1. The test material has a purity of 102%. Five males and five female rat (Sprague-Dawley) were used per test group. The initial body weight ranged from 120 - 144g (males) and 126 - 159g (females) after overnight fasting. The administration was performed by gavage. Three groups, each of ten fasted animals (five males and five females), were given a single oral dose of test material preparation at dose levels of 10, 20 and 40 mg/kg bodyweight. Deaths were noted one, two and five days after dosing. One male treated with 20 mg/kg was killed in extremis on day two. Common signs of toxicity noted in the 20 and 40 mg/kg dose groups were hunched posture, piloerection, lethargy, ptosis, ataxia and loss of righting reflex. Additional signs of toxicity noted in the 40 mg/kg dose group were decreased respiratory rate, body tremors, red/brown stains around the snout, dehydration and pallor of the extremities. Surviving animals appeared normal four days after dosing. Surviving animals showed expected gain in bodyweight during the study. Abnormalities noted at necropsy of animals that died or were killed in extremis during the study were haemorrhagic or abnormally red lungs, dark liver, dark kidneys, haemorrhage of the glandular gastric epithelium and haemorrhage of the small and large intestines. The male treated with 20 mg/kg that was killed in extremis also showed an enlarged and blood filled bladder at necropsy. No abnormalities were noted at necropsy of animals killed at the end of the study.

The LD50 (males and females) was 24 mg/kg bw, the LD50 (males) was 24 mg/kg bw and the LD50 (females) was 25 mg/kg bw.

 

This study was performed according to international guidelines and under GLP and fulfilled the validity criteria. Therefore, this study was considered to be Klimisch 1 study.

 

The obtained results are considered as relevant for the risk assessment.