(1-λ1-oxidanyl-2,2,6,6-tetramethylpiperidin-4-yl) benzoate

Endpoint summary

Description of key information

The skin irritation/corrosion of 4-Hydroxy-TEMPO was tested in a standard OECD 404 guideline study. Classification: not irritating. 
The eye irritation of 4-Hydroxy-TEMPO was tested in a standard OECD 405 guideline study. Classification: H318, Causes serious eye damage.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Remarks:

In vivo study previously available which addresses fully the endpoint requirements.

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-03-02 to 1995-03-30

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD 404)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

May 12, May 1981

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: "Kleine Weiße Russen, Chbb:HM, SPF"

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Chemisch-Pharmazeutische Fabrik, 88400 Biberach an der Riss 1, Germany
- Age at study initiation: adults
- Weight at study initiation: 2.5, 2.6 and 2.5 kg
- Housing: conventional, kept single in stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3°C
- Humidity:30 - 70 %
- Air changes: 15 per h
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 1995-03-06 To: 1995-03-10

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g in 0.5 cm³ water

Duration of treatment / exposure:

4 hours

Observation period:

30 to 60 min, 24, 48 and 72h

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: dorsal trunk
- Coverage: approximately 6 cm²
- Type of wrap if used: gauze, covered by non irritating patch and semiocclusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: yes, warm water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize / Guideline OECD 404

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72h

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72h

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72h

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

4

Interpretation of results:

study cannot be used for classification

Executive summary:

The skin irritation/corrosion of 4-Hydroxy-TEMPO was tested in a standard OECD 404 guideline study. Classification: not irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Remarks:

In vivo study previously available which addresses fully the endpoint requirements.

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-03-09 to 1995-05-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study (OECD 405)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

February 27, 1987

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: "Kleine Weiße Russen, Chbb:HM, SPF"

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Chemisch-Pharmazeutische Fabrik, 88400 Biberach an der Riss 1, Germany
- Age at study initiation: adults
- Weight at study initiation: 2.6, 2.4 and 2.5 kg
- Housing: conventional, kept single in stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3°C
- Humidity:30 - 70 %
- Air changes: 15 per h
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 1995-03-14 To: 1995-07-04

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

Amount applied: 0.1 g

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1, 24, 48, 72 h; 6, 8, 10, 13, 16, 21 and 24 days

Number of animals or in vitro replicates:

3 males

Details on study design:

rinsed with physiological saline solution after 24 h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 24 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

2.33

Max. score:

3

Reversibility:

not fully reversible within: 24 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 16 days

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 13 days

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 24 days

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 13 days

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 16 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 24 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

0.67

Max. score:

2

Reversibility:

not fully reversible within: 24 days

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 24 days

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean)

Time point:

other: 24, 48 and 72h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 21 days

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Remarks:

Migrated information

Conclusions:

The eye irritation of 4-Hydroxy-TEMPO was tested in a standard OECD 405 guideline study. Classification: H318, Causes serious eye damage

Executive summary:

Causes serious eye damage

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In a GLP-compliant OECD guideline 404 study (95-0256-DGT), three male Russian White rabbits were treated with 0.5 g 4-Hydroxy-TEMPO moistened with 0.5 cm³ water using semiocclusive conditions for 4 hours. An application site of approximately 6 cm² was covered with the test substance. The animals were observed for 72 hours and skin changes were recorded for every animal after 30 to 60 minutes, 24, 48 and 72 hours. The application of the test substance to the skin caused a slight edema in one rabbit and a slight erythema in all three rabbits. Signs of edema and erythema fully reversed within 72 hours at the latest. No signs of toxicity were observed. The individual average scores (24 to 72 h) for irritation did not warrant a classification, thus the test substance has to be classified as not irritating according to EU criteria. The study is classified as key study and the results are acceptable.

 

Eye irritation

In a GLP-compliant OECD guideline 405 study (95-0254-DGT), the right eye of three male Russian White rabbits was exposed to 0.1 g 4-Hydroxy-TEMPO, placed as dry substance into the conjunctival sac of the eyelid. Animals were observed after 1, 24, 48 and 72 hour(s) of treatment and 6, 8, 10, 13, 16, 21 and 24 days afterwards. The eyes were washed out with physiological saline solution after 24 hours. Overall, the treatment caused opacity and conjunctivae/chemosis of the eye mucous membranes as well as exsudation and detachment of upper layers of mucosa at 48 h. In 2 of 3 animals the effects were slowly reversible after 13 to 21 days. In one animal hyperaemia, swelling of the conjunctivae and corneal opacity persisted up to day 21. Due to the individual average scores (24 to 72 h) of conjunctivae, chemosis, opacity and iritis the test substance was graded as irritant under the conditions of this study. This GLP-compliant study satisfies the requirements of OECD test guideline 405 and is classified as acceptable (key study).

Justification for selection of skin irritation / corrosion endpoint:
Adequate assay to address endpoint

Justification for selection of eye irritation endpoint:
Adequate assay to address endpoint

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the results for in vivo skin irritation, 4-Hydroxy-TEMPO should be classified as not irritating to skin according to the criteria of EU Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.

Based on the results of the in vivo eye irritation study, the test substance should be classified as Xi, R41 (Irritant, Risk of serious damage to eyes) according to the criteria of EU Directive 67/548/EEC and as Cat. 1, H318 (causes serious eye damage) according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.