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Description of key information

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

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)
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
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 464 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-03-02 to 1995-03-16
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A well conducted study done in compliance with GLP. Screening study using one dose and two animals.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Screening study using one dose and two animals. Necropsy not conducted.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals
- Age at study initiation: 16 months
- Weight at study initiation: male: 2.3 kg; female: 2.8 kg
- Housing: Suspended wire cages
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: at least 10% of body surface
- Type of wrap if used: gauze patch (4x6 inches); plastic; tape

TEST MATERIAL
- Amount(s) applied: 2,000 mg/kg
Duration of exposure:
24 hours
Doses:
2,000 mg/kg
No. of animals per sex per dose:
1 male, 1 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations -daily; body weight - weekly
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight, skin irritation
Preliminary study:
Not performed
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
0/2
Clinical signs:
Lethargy, diarrhea, soiling
Body weight:
Normal
Other findings:
Skin irritation - day 1 - well defined erythema/very slight to slight edema ; day 7 - very slight to well defeined erythema/very slight or no edema
day 14 - very slight or no erythema/no edema

The results are summarised in the tables below:

Mortality

Dose Level

No. Treated

No. Dead

mg/kg

M/F

M/F

2000

1/1

0/0

 

Body weights, dose volume and dermal reactions

Ear tag no/sex

Dose Volume

Body weights

Dermal Reactions

% Rem.

cc

Day 0

Day 14

Day 1

Day 7

Day 14

R

E

R

E

R

E

E1884/M

5.1

2.3

2.6

2a

1

1a

0

0ab

0

80

E1892/F

6.2

2.8

2.9

2a

2

2a

1

1a*

0

80

 

Key

R            erythema

E             edema

a             dose area stained brown

b            skin area appeared dry

*            animal re-clipped

% rem  %remaining – visual estimate of the amount of material remaining on the skin, gauze and occlusive binding at 24 hours after the binding was removed.

 

Draize Dermal Scoring Code

Erythema and Eschar Formation:

No erythema                                                  0

Very slight erythema (barely perceptible)         1

Well defined erythema                                     2

Moderate to severe erythema                          3

Severe erythema (beet redness) to slight          4

eschar formation (injuries in depth).

 

Edema Formation:

No edema                                                      0

Very slight edema (barely perceptible)            1

Slight edema (edges of area well-defined by    2

 Definite raising)

Moderate edema                                            3

(raised approximately 1.0mm)

Severe edema (raised more than 1.0mm,         4

extending beyond the area of exposure)

 

Physical Signs

Animal E1884-M had diarrhea and/or soiling of the anogenital area on days 8 through 10. Animal E1892-F appeared lethargic on the day of dosing but returned to normal by day 1.

Interpretation of results:
GHS criteria not met
Conclusions:
2,2,6,6-Tetramethyl-4-oxopiperidinooxy administered topically to two rabbits for 24 hours resulted in no mortality. Clinical signs of toxicity during the 14 day observation period included lethargy and diarrhea. Necrospy was not conducted. Based on the results of the study the LD50 is greater than 2000mg/kg/bodyweight
Executive summary:

A GLP study was conducted to assess the effect of 2,2,6,6-tetramethyl-4 -oxopiperindinooxy when applied dermally. Two New Zealand white rabbits (one, male and one female) were treated with a single dose of 2000mg/kg/bw of the test substance. After a contact period of 24 hours the test substance was removed with distilled water. The animals were observed 1, 2 and 4 hours post dose, once daily for 14 days for toxicity and pharmacological effects and twice daily for mortality. Body weights were recorded pre-test, weekly and at termination.

No mortalities were observed during the test period. Instances of lethargy, diarrhea and soilng of the anogenital area were noted during the observation period. Bodyweight changes were normal. Dermal reactions were well defined on day 1, were slight to well defined on day 7 and absent to slight on day 14.

On the basis of the study results the LD50 was defined as >2000mg/kg/bw.

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

Additional information

Justification for selection of acute toxicity – oral endpoint
One study available but was considered to be of good quality.

Justification for selection of acute toxicity – dermal endpoint
One study available but was considered to be of good quality and sufficient to demonstrate that the LD50 was greater than 2000mg/kg/bw and that no classification for dermal toxicity is required.

Justification for classification or non-classification

The available data summarised above demonstrates that 2,2,6,6-tetramethyl-4-oxopiperidinooxy does not required classification as toxic via the dermal route, according to Directive 67/548/EC (DSD) or Regulation (EC) No 1272/2008. However, classification is required with respect to the oral toxicity. According toRegulation (EC) No 1272/2008, the classification ‘Acute toxicity 4, H302 Harmful if swallowed’ should be applied.