5-[(4-carboxybutanoyl)peroxy]-5-oxopentanoic acid

Endpoint summary

Description of key information

The test item is not skin irritating, but severely eye damaging.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1993

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

1992

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne
- Age at study initiation: 15 weeks
- Weight at study initiation: 3057 - 3151 g
- Housing: Standard Laboratory Conditions (Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls, with haysticks and wood for gnawing)
- Diet: Pelleted standard Kliba 3410 ("Kliba", Kliba Miihlen AG, 4303 Kaiseraugst, Switzerland) rabbit maintenance diet ad libitum (batch no. 61/98).
- Water: Community tap water from Itingen, ad libitum, in water bowls. Results of analysis are archived by RCC.
- Acclimation period: Four days under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3°C
- Humidity (%): relative humidity 40-70% (values above 70% during cleaning process possible)
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle. Recorded music was played for approximately 8 hours during the light period

IN-LIFE DATES:
Delivery of the animals: 09 June 1998
Acclimatization: 10-14 June 1998
Treatment: 15 June 1998
Observation: 15-30 June 1998
Euthanasia of the animals: 30 June 1998

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent no treatment

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5g per animal

VEHICLE
the solid test item was moistened with bidistilled water

Duration of treatment / exposure:

4h

Observation period:

14 days

Number of animals:

3 animals: 2 females, 1 male

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- Type of wrap: surgical gauze and a semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: flushed with lukewarm tap water
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
mortality and clinical signs daily, body weight at start of acclimatization, on the first day of application and at termination of observation

SCORING SYSTEM:
- Method of calculation:
The skin reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours as well as 7 and 14 days after the removal of the dressing, gauze patch and test article. If evident, corrosive or staining properties of the test article were described and recorded.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 1.33. Local signs (mean values from 24 to 72 hours) consisted of grade 1.33 erythema and grade 0.00 edema. Very slight to well-defined erythema was noted in all animals. This finding was reversible in two animals after 7 days, but persisted in the third animal after 14 days.
No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred. No staining by the test article of the treated skin was observed.
The body weight of all rabbits were considered to be within the normal range of variability.

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results obtained in this study according to OECD 404, the test substance does not possess any primary irritating properties to the skin of albino rabbits under the test conditions chosen.

Executive summary:

In this study, the potential irritant and/or corrosive effects of the test substance were evaluated on the skin of New Zealand White rabbits according ot OECD 404. Each of three rabbits received a 0.5g dose of the test article to 6 cm² intact dorsal skin. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours as well as 7 and 14 days after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion. The irritation score was calculated per animal at 24, 48 and 72 hours, summed up and then dividing by the number of data points. The irritation score for erythema was 1.33 for all three animals (max. 8.0). This finding was reversible in two animals after 14 days, but persisted in the third animal after 14 days. Local signs (mean values from 24 to 72 hours) consisted also of grade 0.00 edema. The test article did not cause staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval. The test article is not considered to be "irritating" to rabbit skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1992

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source:Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne
- Age at study initiation: 15 weeks
- Weight at study initiation: 2738 - 3158 g
- Housing: Standard Laboratory Conditions (Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls, wood and haysticks for gnawing)
- Diet: Pelleted standard Kliba 3410 ("Kliba", Kliba Muhlen AG, .4303 Kaiseraugst, Switzerland) rabbit maintenance diet ad libitum (batch no. 61/98).
- Water: Community tap water from Itingen, ad libitum, in water bowls.
- Acclimation period: Five days under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3°C
- Humidity (%): 40-70% (values above 70% during cleaning process possible)
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): The room was illuminated by fluorescent light on a 12 hour light/dark cycle. Recorded music was played for approximately 8 hours during the light period.

IN-LIFE DATES:
Delivery of the animals: 16 June 1998
Acclimatization: 17-21 June 1998
Treatment: 22 June 1998
Observation: 22 June-13 July 1998
Euthanasia of the animals: 13 July 1998

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1g per animal undiluted

Duration of treatment / exposure:

The treated eyes were not rinsed after application.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3 animals: 2 females, 1 male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM :The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel / Switzerland).

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks:

after 7 days: score 3

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

Application of the test article to healthy rabbit conjunctivae resulted in a primary irritation score of 4.33.
No corrosion of the comea was observed at any of the reading times. No staining of the cornea, sclera or conjunctivae by the test article was observed.

Other effects:

The body weight of all rabbits were considered to be within the normal range of variability.
No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

Interpretation of results:

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

Conclusions:

Under the conditions of the test according to OECD 405, the test substance is considered to be severely damaging the rabbit eye.

Executive summary:

In this study, the potential irritant and/or corrosive effects of the test substance were evaluated on the eyes of New Zealand White rabbits according ot OECD 405. Each of three rabbits received a 0.1g dose of the test article in the conjunctival sac of the left eye. The treated eyes were not rinsed after application. The contralateral eye of each animal remained untreated and served as a control. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours as well as 7, 14 and 21 days after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. No staining of the comea or sclera of the treated eyes by the test article was observed. The mean score (24/48/72h) for cornea opacity was between 0 and 1, not fully reversible in one animal; for conjunctivae the mean score was between 1.66 and 2, fully reversible within 14 days;chemosis score between 0.66 and 2.66, fully reversible within a maximum of 14 days. No corrosion was observed at any of the measuring intervals. Based upon the degree of chemosis and the persistent corneal opacity noted in one animal after 21 days the test item is considered to be severely eye damaging to the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

OECD 404

In this study, the potential irritant and/or corrosive effects of the test substance were evaluated on the skin of New Zealand White rabbits according ot OECD 404. Each of three rabbits received a 0.5g dose of the test article to 6 cm² intact dorsal skin. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours as well as 7 and 14 days after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion. The irritation score was calculated per animal at 24, 48 and 72 hours, summed up and then dividing by the number of data points. The irritation score for erythema was 1.33 for all three animals (max. 8.0). This finding was reversible in two animals after 14 days, but persisted in the third animal after 14 days. Local signs (mean values from 24 to 72 hours) consisted also of grade 0.00 edema. The test article did not cause staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval. The test article is not considered to be "irritating" to rabbit skin.

OECD 405

In this study, the potential irritant and/or corrosive effects of the test substance were evaluated on the eyes of New Zealand White rabbits according ot OECD 405. Each of three rabbits received a 0.1g dose of the test article in the conjunctival sac of the left eye. The treated eyes were not rinsed after application. The contralateral eye of each animal remained untreated and served as a control. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours as well as 7, 14 and 21 days after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. No staining of the comea or sclera of the treated eyes by the test article was observed. The mean score (24/48/72h) for cornea opacity was between 0 and 1, not fully reversible in one animal; for conjunctivae the mean score was between 1.66 and 2, fully reversible within 14 days;chemosis score between 0.66 and 2.66, fully reversible within a maximum of 14 days. No corrosion was observed at any of the measuring intervals. Based upon the degree of chemosis and the persistent corneal opacity noted in one animal after 21 days the test item is considered to be severely eye damaging to the rabbit eye.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on eye irritation, the test item is classified and labelled as severely eye damaging Cat 1 (H318: Causes serious eye damage) according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin irritation,the test item is not classified and labelled as skin irritating according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.