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Description of key information

Oral (OECD 401), rat: LD50 calculated = 1203 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 Oct - 14 Nov 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
no data on analytical purity of test substance given
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
yes
Remarks:
no data on analytical purity of test substance given
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. 4 - 6 weeks
- Weight at study initiation: 119-171g (males) and 111-157g (females)
- Fasting period before study: Animals were fasted overnight prior to and approximately two hours after administration.
- Housing: groups of five in polypropylene cages, sawdust bedding
- Diet: standard laboratory rodent diet, Rat and Mouse Expanded Diet Number 1 (Special Diet Services Limited, Witham, England), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 55 -70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
other: undiluted (range-finder study: 2000 and 5000 mg/kg bw) or in arachis oil (range-finder study: 500 mg/kg bw and main study)
Details on oral exposure:
VEHICLE
- Amount of vehicle: main study: 5 mL/kg bw; range-finder study: 5.05 mL/kg bw (for 5000 mg/kg bw), 2.02 mL/kg bw (for 2000 mg/kg bw) and 5 mL/kg bw (for 500 mg/kg bw)

MAXIMUM DOSE VOLUME APPLIED: main study: 5 mL/kg bw; range-finder study: 5.05 mL/kg bw
Doses:
range-finder study: 500, 2000 and 5000 mg/kg bw
main study: 500, 794, 1260 and 2000 mg/kg bw
No. of animals per sex per dose:
range-finder study: 2
main study: 5
Control animals:
no
Details on study design:
Range-finder study:
- Duration of observation period following administration: 5 days

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 0.5, 1, 2, 3, 4 and 5 hours following dosing and then at least once daily for 14 days. Bodyweights were recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
LD50 and 95% confidence limits of the test material were calculated using the method of Weil C.S. (1952) Biometrics 8, 249.
Preliminary study:
500 mg/kg bw: 0/4 animals died
2000 mg/kg bw: 4/4 animals died within 2 days after dosing
5000 mg/kg bw: 4/4 animals died within 24 h after dosing
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 203 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 035 - <= 1 400
Remarks on result:
other: LD50 was calculated according to method of Weil (1952)
Sex:
male
Dose descriptor:
approximate LD50
Effect level:
ca. 1 260 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Due to mortality pattern obtained, it was not possible to calculate an LD50 for males only.
Sex:
female
Dose descriptor:
LD50
Effect level:
1 097 mg/kg bw
Based on:
test mat.
95% CL:
>= 912 - <= 1 320
Remarks on result:
other: LD50 was calculated according to method of Weil (1952).
Mortality:
500 mg/kg bw: 0/5 males and 0/5 females died
794 mg/kg bw: 0/5 males and 0/5 females died
1260 mg/kg bw: 2/5 males and 4/5 females died within 24 h after dosing
2000 mg/kg bw: 5/5 males and 5/5 females died within 24 h after dosing
Clinical signs:
Signs of reaction to treatment observed shortly after dosing in rats at all dose levels were pilo-erection, hunched posture, lethargy, a decreased respiratory rate and ptosis. Other signs of toxicity observed in rats at some dose levels included ataxia (at 500 and 2000 mg/kg bw), wet fur an the dorsal surface (at 794, 1260 and 2000 mg/kg bw), gasping respiration (at 2000 mg/kg bw) and loss of the righting reflex (at 2000 mg/kg bw). Recovery of survivors, as judged by external appearance and behaviour was apparently complete by Day 7.
Body weight:
No effect on body weight was noted.
Gross pathology:
Abnormalities noted at necropsy of animals that died during the study were haemorrhage of the lungs, inflammation of the glandular region of the stomach and small intestine and injection of the blood vessels of the small intestine. Haemorrhage of the small intestine was seen in one female at 2000 mg/kg bw and ulceration of the non-glandular region of the stomach was seen in one female at 1260 mg/kg bw. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Table 1. Results of the acute oral toxicity study.

Dose level (mg/kg bw)

Mortalities

 

Male

Female

500

0/5

0/5

794

0/5

0/5

1260

2/5

4/5

2000

5/5

5/5

Interpretation of results:
other: Acute Tox. Cat. 4 according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in rats a LD50 value for males and females combined of 1203 mg/kg bw was calculated according to the method of Weil (1952).
Executive summary:

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 401 and in compliance with GLP (1984). Based on a preliminary study, groups of 5 male and 5 female rats were given dose levels of 500, 794, 1260 and 2000 mg/kg bw via gavage. No mortality occurred at 500 and 794 mg/kg bw. 6/10 animals died at 1260 mg/kg bw and all animals were found moribund within 24 h at 2000 mg/kg bw. Thus, a LD50 value of 1203 mg/kg bw for male and female rats combined was calculated to the method of Weil (1952).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 203 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 401 and in compliance with GLP (1984). Based on a preliminary study, groups of 5 male and 5 female rats were given dose levels of 500, 794, 1260 and 2000 mg/kg bw via gavage. No mortality occurred at 500 and 794 mg/kg bw. 6/10 animals died at 1260 mg/kg bw and all animals were found moribund within 24 h at 2000 mg/kg bw. Thus, a LD50 value of 1203 mg/kg bw for male and female rats combined was calculated to the method of Weil (1952).

Justification for classification or non-classification

The available data on acute oral toxicity meet the criteria for classification as Acute Tox 4 (H302) according to Regulation (EC) 1272/2008.