Registration Dossier

Administrative data

Description of key information

oral: LD50 >2000mg/kg bw, male and female rat, EU Method B.1, Toxicol Laboratories Limited 1992

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:
1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Performed under GLP and the method followed is similar to a recognised guideline.
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)BR strain (VAF plus)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: 4-6 weeks
- Weight at study initiation: males 100-113g; females 109 - 116g
- Fasting period before study: overnight before dosing
- Housing: Animals were housed in groups of 5, by sex, in grid bottomed cages suspended over cardboard lined excreta trays. cardboard tray liners were changed as often as necessary to maintain hygiene.
- Diet (e.g. ad libitum): pelleted diet ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 32-52
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hour dark / 12 hours light
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10ml/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were examined shortly after dosing and approximately 30 minutes, 1, 2 and 4 hours after dosing and daily thereafter for 14 consecutive days. On the day of dosing all animals were weighed in order to calculate the amount of test article to be administered. They were weighed again on day 8 and on day 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female was euthanasied on day 2 as death was considered to be inevitable. The remaining animals survived to the end of the study.
Clinical signs:
A hunched posture was seen in all females and most males from day 1, but by day 3 all surviving animals appeared to be outwardly healthy.
Body weight:
There was no adverse effect on bodyweight gain in surviving animals of either sex.
Gross pathology:
No significant findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test substance in male and female Crl:CD(SD)BR strain (VAF plus) of rat was estimated to be greater than 2000 mg/kg body weight.
Executive summary:

The test material was administered as a single oral dose, by gavage, at a dose level of 2000 mg/kg bodyweight to a group of 5 male and 5 female rats following an overnight fast. The animals were observed for 14 days and survivors were then euthanized. All animals were subject to necropsy. One female was humanely euthanized as death was considered to be inevitable; all remaining animals survived to the end of the study. Clinical signs of toxicity were noted in most animals on the day of dosing, but all surviving animals appeared outwardly healthy from day 3 onwards. There was no adverse effect on bodyweight gain in animals of either sex. Necropsy findings were of low incidence and are considered not to be significant. When administered as a single oral dose of 2000 mg/ kg bodyweight, the test material produced some evidence of toxicity in the rat. The LD50 for both sexes combined is estimated to be in excess of 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

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

Acute oral:

The test material was administered as a single oral dose, by gavage, at a dose level of 2000 mg/kg bodyweight to a group of 5 male and 5 female rats following an overnight fast. The animals were observed for 14 days and survivors were then euthanized. All animals were subject to necropsy. One female was humanely euthanized as death was considered to be inevitable; all remaining animals survived to the end of the study. Clinical signs of toxicity were noted in most animals on the day of dosing, but all surviving animals appeared outwardly healthy from day 3 onwards. There was no adverse effect on bodyweight gain in animals of either sex. Necropsy findings were of low incidence and are considered not to be significant. When administered as a single oral dose of 2000 mg/ kg bodyweight, the test material produced some evidence of toxicity in the rat. The LD50 for both sexes combined is estimated to be in excess of 2000 mg/kg.


Justification for selection of acute toxicity – oral endpoint
Study selected is an in vivo study (Klimisch 2)

Justification for classification or non-classification

The substance does not meet classification criteria under EU Directive 67/548/EEC for acute toxicity.

The substance does not meet classification criteria under Regulation (EC) No 1272/2008 for acute toxicity.