Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 - 23 May 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No information on purity was given.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
yes
Remarks:
no information on purity
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. 4 - 6 weeks
- Weight at study initiation: 120 - 152 g (males), 107 - 137 g (females)
- Fasting period before study: overnight prior to dosing until approx. 2 h after dosing
- Housing: 5 animals of the same sex per cage in polypropylene cages on sawdust
- Diet: Rat & Mouse Expanded Diet No. 1 (Special Diet Services Limited, Witham, UK), ad libitum
- Water: mains tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 ± 2.5
- Humidity (%): 45 - 60
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
A range-finding study was carried out to establish a dosing regimen for the main study.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
Range-finding study: 25, 200, 2000 and 5000 mg/kg bw
Main study: 5000 mg/kg bw
No. of animals per sex per dose:
Range-finding study: 2
Main study: 5
Control animals:
no
Details on study design:
Range-finding study:
- Duration of observation period following administration: 7 days
- Frequency of observations: Animals were observed 0.5, 1 and 4 h after administration and subsequently once daily for 7 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 h after administration and subsequently once daily for 14 days. Individual body weights were determined on Days 0, 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period of the range-finding study and the main study.
Clinical signs:
Range-finding study:
Abnormal body carriage (hunched posture) and pilo-erection were observed in all rats at all dose levels. Lethargy and ataxia were seen in rats at the 2000 mg/kg bw dose level and above while ptosis and a decreased respiratory rate were recorded at the 5000 mg/kg bw dose level only. Recovery of all animals at the 25 and 200 mg/kg bw dose levels, as judged by external appearance and behaviour, was apparently complete 4 h following dosing. All animals at the 2000 and 5000 mg/kg bw dose levels had recovered by Day 1 with the exception of one male rat, at the higher dose level, in which symptoms persisted until Day 1
but had resolved completely by Day 2.

Main study:
Signs of reaction to treatment observed shortly after dosing in all rats consisted of an abnormal body carriage (hunched posture), pilo-erection and ataxia. Other signs of overt toxicity seen in some rats consisted of lethargy, ptosis and a decreased respiratory rate. Recovery of all animals, as judged by external appearance and behaviour was apparently complete by Day 2.
Body weight:
Body weight development was unremarkable. All animals gained weight during the observation period.
Gross pathology:
Post mortem examination of all rats killed at Day 14 revealed congestion of the lungs in two rats only. No macroscopic abnormalities were observed in any of the remaining animals.

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study a LD50 value > 5000 mg/kg bw in male and female rats was derived.
Executive summary:

An acute oral toxicity study was performed with male and female rats according to OECD 401 under GLP conditions. After a range-finding study with the dose levels 25, 200, 2000 and 5000 mg/kg bw, a main study with 5000 mg/kg bw was performed. No mortality occurred during the study period of the range-finding study and the main study.

In this acute oral toxicity study a LD50 value > 5000 mg/kg bw in male and female rats was derived.