Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-01-02 to 1997-02-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A well conducted study according to guidelines and done in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 4-Oxotempo
- Physical state: Liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd Margate, Kent
- Age at study initiation: 8-12 weeks
- Weight at study initiation: M:220-233g; F:200-225g
- Fasting period before study:overnight
- Housing:polypropylene cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19-22
- Humidity (%):44-54
- Air changes (per hr):15
- Photoperiod (hrs dark / hrs light):12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Doses:
1,000 mg/kg
1,414 mg/kg
2,000 mg/kg
No. of animals per sex per dose:
1,000 mg/kg - 5 females
1,414 mg/kg - 5 females
2,000 mg/kg - 5 male, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Thompson, W.R. (1947)

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
1 464 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 235 - <= 1 735
Mortality:
1,000 mg/kg - 0/5
1,414 mg/kg - 2/5
2,000 mg/kg - 5/5 (females)
2,000 mg/kg - 5/5 (males)
All animals died by day 4.
Clinical signs:
All groups - hunched posture;
1,414, 2000 mg/kg - ataxia, lethargy, ptosis, decreased respiratory rate, labored respiration body tremors, splayed gait, convulsions;
2,000 mg/kg - loss of righting reflex
Body weight:
No effects in survivors.
Gross pathology:
Animals that died during the study - hemorrhagic or abnormally red lungs, dark liver and dark kidneys
Surviving animals - no changes

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute oral LD50 of 2,2,6,6-tetramethyl-4-oxopiperidinooxy in rats was 1,464 mg/kg.
Executive summary:

A GLP study was performed to assess the toxicity of 2,2,6,6-tetramethyl-4-oxopiperidinooxy when administered orally. The study was performed in accordance with OECD guideline 401. Following a range finding study, three groups of five fasted females were dosed with a single dose of test material. The doses were administered as a dispersion in water at levels of 1000, 1414 and 2000mg/kg/b w. An additional group of five fasted males were treated with 2000mg/kg/bw in order to illustrate that one sex was not more sensitive that the other. The animals were observed for 14 days after dosing. All animals were subject to a gross pathological examination.

All animals, male and female, in the high dose group died by day 4, two animals in the 1414mg/kg/bw dose group died, one on day 1 and the other day 4, no deaths were observed in the 1000mg/kg/bw group. Common signs of systemic toxicity noted were ataxia, hunched posture, lethargy, ptosis, decreased respiratory rate and laboured respiration with additional signs or incidents of clonic or tonic convulsions, pilo-erection, loss of righting reflex, occasional body tremors and splayed gait.

Surviving animals recovered two days after dosing except for one female which appeared normal throughout the study. No abnormality was observed with respect to weight gain.

Abnormalities noted at necropsy of animals that died during the course of the study were haemorrhagic or abnormally red lungs, ark liver and dark kidneys. No abnormalities were observed in animals that were terminated at the end of the study.

The acute oral median lethal dose and 95% confidence limits were calculated by the method of Thompson W R to be 1464 (1235 – 1735) mg/kg/bw for females only.