Registration Dossier

Administrative data

Description of key information

In vivo data reports mild-moderate irritation after extended exposure periods  which appear to be reversible. Comparisons with similar molecules reported in the literature conclude the substance to be non-irritating. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Executive summary:

The cutaneous reaction to various nitroxides has been reviewed by Fuchs (2000) in Toxicology of the Human Environment, the Critical Role of Free Radicals, Ed. Christopher J Rhodes, Taylor & Francis London pages 139-152

 

This includes the reaction of Tempo and similar molecules to both animal and human skin. Uniformly slight or non-irritant properties have been described. In addition, for Butoxy Tempo the skin irritation potential (Mullaney T, 2006, Report No 1156/038 ) has been shown to be slight (or non-irritant).

 

The introduction of an additional substituent at the 4-position was therefore shown not to influence the irritation overall and thus on structure/function grounds Oxo-Tempo is considered to be non-irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
In vivo study available.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-04-07 to 1997-04-12
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 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Chesire, UK
- Age at study initiation:12-16 weeks
- Weight at study initiation: 2.6-3.04 kg
- Housing:Suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-22
- Humidity (%): 43-56
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 ml


Duration of treatment / exposure:
The upper and lower eyelids were held together for about one second immediately after instillation, to prevent loss of
the test material, and then released.
Observation period (in vivo):
1, 24, 48, 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Draize

Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Remarks:
group
Time point:
other: 1 hour
Score:
8.7
Max. score:
18
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Kay and Calandra Classifiation System
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
2,2,6,6-Tetramethyl-4-oxopiperidinooxy instilled into the eyes of three rabbits resulted in mild to moderate conjunctival irritation, diffuse corneal
opacity and iridial inflammation. All effects cleared by 48 or 72 hours. The test material was mildly irritating according to the Kay and Calandra
classification system. It was not classified as irritating by OECD GHS standards.
classified as irritating by OECD GHS criteria.
Executive summary:

A GLP study was performed in accordance with OECD guideline 405, to assess the effect of 2,2,6,6,-tetramethyl-4 -oxopiperindinooxy when administered to the eye.

 A single dose of 0.1 ml of test material was applied to the right eye of three New Zealand white rabbits. Assessment of the animals was made at 1 hour, 24, 48 and 72 hours after treatment.

The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye using a modified Kay and Calandra classification system.

No classification with respect to eye irritancy is required.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The cutaneous reaction of various nitroxides was reviewed by Fuchs (2000) and concluded, based on comparison with similar molecules and structural information, that 2,2,6,6-tetramethyl-4-oxopiperidinooxy was not irritating.

Dermal effects were reported in the acute dermal toxicity study (Cerven, D.R 1995). After 24 hours, exposure to a single dose of 2000mg/kg bw two New Zealand white rabbits showed an average score of 2 for erythema and 1.5 for oedema using the Draize Dermal Scoring codes. Although not fully reversible in the 14 day observation period, significant reversal was observed.

Topical sighting tests performed with guinea pigs during a skin sensitisation study (Allen, D.J, 1997), reported mild – moderate irritation after 24 and 48 hours exposure periods with, amongst other concentrations, undiluted test substance. The effects observed were fully reversible within the 48 hour observation period.

Although mild- moderate irritation was observed in the studies, the exposure periods were far in excess of the 4 hours cited in OECD 404, Acute Dermal Irritation/Corrosion. It is reasonable to expect that should a skin irritation study be performed in accordance with OECD 404, the effects to the skin would be milder than observed in the dermal acute and skin sensitisation studies reported.

A single study is available to determine the effects on the eye.A GLP study in accordance with OECD guideline 405, applied a single dose of 0.1 ml of test material to the right eye of three New Zealand white rabbits. Assessment of the animals was made at 1 hour, 24, 48 and 72 hours after treatment. The test material produced a maximum group mean score of 8.7 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye using a modified Kay and Calandra classification system.

In conclusion mild irritation to the eye was observed but was not sufficiently severe to trigger classification.

 


Justification for selection of skin irritation / corrosion endpoint:
Weight of evidence demonstrates that the criteria for irritating to skin are not met.

Justification for selection of eye irritation endpoint:
A single study was available which was considered to be of adequate quality to fulfil the data requirement.

Justification for classification or non-classification

The criteria for skin irritation/corrosion and eye irritation according to Regulation (EC) No 1272/2008 are not met. No classification with respect to skin irritation/corrosion or eye irritation is required.