Registration Dossier

Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:
Not performed
Effect levels
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

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.