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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:
From 08 to 23 March 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to EU guideline 84/449/EC in compliance with GLP. Analytical certificate not included in study report.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: EU guideline 84/449/EC of 19/09/1984
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchem, Germany
- Age at study initiation: 9 (males) or 10 (females) weeks
- Weight at study initiation: 172 (males) or 173 (females) g
- Fasting period before study: 16 to 4 h before test begin
- Housing: Makrolon Type III cages
- Diet (e.g. ad libitum): Fixed formula standard diet Altromin 1324 pellets (Altromin GmbH)
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 50 +/- 10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 ml/kg bw
Doses:
1,000 (only females), 2,000, 3,100 and 5,000 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: Several times on the day of dosing then twice daily until test end: type, onset, duration and intensity of symptoms and mortality. Predosing, after one week and at test end: bodyweight
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
According to Rosiello AP et al. (1977), J. Tox. Environ. Health 3:797, modified by Pauluhn J (Bayer AG, report no. 11835, 1983). Based on maximum likelihood method of Bliss CI (1938), Q. J. Pharm. Pharmacol. 11:92.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

Any other information on results incl. tables

As of 3,100 (males) and 2,000 (females) mg/kg bw, observed symptoms included poor general condition, rough fur, sedation, unconsciousness, side or stomach position, paralysis-like effects in the posterior extremities. High gait was seen in males at 5,000 mg/kg bw and females at 2,000 and 5,000 mg/kg bw. Bloody nose and weight loss were observed in females at 2,000 mg/kg bw. In one female at 3,100 mg/kg bw, there was shortness of breath.

In males at 5,000 mg/kg bw and females as of 3,100 mg/kg bw which died before test end, gross macroscopical examination revealed damaged mucous membrane of the stomach, redenned stomach fundus, as well as redenned and swollen gastro-intestinal tract. One male and 2 females at 5,000 mg/kg bw also displayed redenned lungs.

There were no symptoms at 2,000 (males) and 1,000 (females) mg/kg bw.

Applicant's summary and conclusion

Conclusions:
Under the conditions of the study, the acute oral LD50 of the substance was 5,000 mg/kg bw for males and > 2,000 mg/kg bw for females.
Executive summary:

A study was conducted to determine the acute oral toxicity of NPEO to rat in accordance with EU Guideline 84/449/EC of 19/09/1984. Male and female Wistar rats received the test substance diluted in polyethylene glycol via gavage at doses of 1,000 (females only), 2,000, 3,100 and 5,000 mg/kg bw. Mortality and clinical signs were recorded throughout the study. Gross macroscopy was conducted at the end of the test period. As of 3,100 (males) and 2,000 (females) mg/kg bw, symptoms included poor general condition, rough fur, sedation, unconsciousness, side or stomach position, paralysis-like effects in the posterior extremities. High gait was seen in males at 5,000 mg/kg bw and females at 2,000 and 5,000 mg/kg bw. Bloody nose and weight loss were observed in females at 2,000 mg/kg bw. In one female at 3,100 mg/kg bw, there was shortness of breath. In males at 5,000 mg/kg bw and females as of 3,100 mg/kg bw which died before test end, gross macroscopical examination revealed damaged mucous membrane of the stomach, redenned stomach fundus, as well as redenned and swollen gastro-intestinal tract. One male and 2 females at 5,000 mg/kg bw also displayed redenned lungs. Under the conditions of the study, the acute oral LD50 of the substance was 5,000 mg/kg bw for males and > 2,000 mg/kg bw for females (Ivens-Kohl I, 1988).