Peracetic acid

Endpoint summary

Description of key information

Skin

Peracetic acid  < 1%: not irritating (human studies, Draize-Test)

1% < peracetic acid  < 3%: irritating (OECD 404, rabbit)

3% < peracetic acid > 5%: corrosive (OECD 404, rabbit)

Eyes

Peracetic acid  < 1%: not irritating (OECD 405)

1% < peracetic acid  < 3%: irritating

peracetic acid  >= 3%: corrosive

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Strain: New Zealand White
- Sex: male
- Source: HSD/CPB, Zeist, The Netherlands
- Weight at study initiation: 2.5 - 3.0 kg
- Number of animals: 3 (1 per test compound)

Type of coverage:

occlusive

Preparation of test site:

other: clipped free of hair

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

- Area of exposure: test material was introduced under a 6 cm^2 gauze patch covered by aluminium foil secured by adhesive tape
- Concentration in vehicle: all products were used undiluted, therefore the peracetic acid concentrations were 40 % (Proxitane 4002), 15 % (Proxitane 1507) and 5 % (Proxitane 0512)
- Total volume applied: 0.5 mL
- Removal of test substance: yes, after four hours of exposure the patches were removed and the skin was wiped

Duration of treatment / exposure:

4 hour(s)

Observation period:

14 days postexposure

Number of animals:

3

Details on study design:

Examinations: The resulting skin reactions were evaluated at 30-60 minutes and 24, 48 and 72 hours after patch removal.

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

No individual scores given, but general assessment of irritation available. Effects found were discolouration, edema, brown crust. The degree of damage between the 3 formulations was comparable.

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

No individual scores given, but general assessment of irritation available. Effects found were discolouration, edema, brown crust. The degree of damage between the 3 formulations was comparable.

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

No individual scores given, but general assessment of irritation available. Effects found were discolouration, edema, brown crust. The degree of damage between the 3 formulations was comparable.

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

No individual scores given, but general assessment of irritation available. Effects found were discolouration, edema, brown crust. The degree of damage between the 3 formulations was comparable.

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

No individual scores given, but general assessment of irritation available. Effects found were discolouration, edema, brown crust. The degree of damage between the 3 formulations was comparable.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

No individual scores given, but general assessment of irritation available. Effects found were discolouration, edema, brown crust. The degree of damage between the 3 formulations was comparable.

Irritant / corrosive response data:

Effects found were discolouration, edema, brown crust. The degree of damage between the 3 formulations was comparable.

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

All three substances are considered to be corrosive to the rabbit skin.
Classification: corrosive (causes burns)

Executive summary:

In order to study the irritating/corrosive effects of three peracetic acid containing formulations (Proxitane 0512, Proxitane 1507 and Proxitane 4002) to the skin, 3 rabbits were dermally treated with the test materials. Because of the expected skin damaging properties only 1 animal per test material was used. Samples of 0.5 mL were applied on the shaven non-abraded skin of male rabbits and occluded under patches for 4 hours. 30 minutes after application the occlusion was temporarily removed treated and skin areas were examined. After removing the patches, scoring of the oedema and erythema was made at 30-60 minutes and 24, 48 and 72 hours after removal. The animals were observed until day 14 after application.

 

30 minutes after application (while the patches were still in place) the skin was oedematous and had turned white in each animal. Half an hour after removing the patches, there was a hard dry crusty white/yellow area observed at the areas treated with Proxitane 1507 and Proxitane 4002 which persisted until day 14 of the study, although it slowly turned brown. The animal that was treated with Proxitane 0512 showed a weak large white oedematous area at 30 minutes after removing the patch, which turned yellow with brown crusts after 24 hours. After 48 hours there were still some oedematous areas surrounded by a dry yellow crust. The oedema subsided after 72 hours; however, brownish-yellow crusts were still noted after 14 days.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Application was only 3 and 45 minutes. However, due to the known corrosive properties of the test material this seems justified, especially with respect to animal welfare.

Principles of method if other than guideline:

Application was only 3 and 45 minutes. However, due to the known corrosive properties of the test material this seems justified, especially with respect to animal welfare.

GLP compliance:

yes

Species:

rabbit

Strain:

other: White Russian albino

Details on test animals or test system and environmental conditions:

- Source: Asta Pharma AG, Bielefeld, Germany
- Sex: males and females
- Age: 4-6 months
- Weight: 2.2 – 2.6 kg
- Number of animals per group: 3

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: undiluted test substance

Controls:

other: not applicable

Amount / concentration applied:

- Concentration: 5 %
- Application volume: 0.5 mL

Duration of treatment / exposure:

3 and 45 minutes resp.

Observation period:

14 days (3 minutes exposure), 24 hours (45 minutes exposure)

Number of animals:

6 (3 per group)

Details on study design:

- Sex: 4 males, 2 females
- Controls: an area of the dorsal skin was treated in the same way but without test substance
- Area of exposure: 0.5 mL of the test substance was spread over a gauze square measuring approx. 6.25 cm^2 and placed on the animal's skin.
- Removal of test substance: after 3 and 45 minutes resp. the remaining test material was gently washed off
- Scoring system: according to OECD guideline 404
- Examination time points: Time of exposure - 3 minutes: 1, 24, 48 and 72 hours after removal of the patches, thereafter once daily; Time of exposure - 45 minutes: 1 and 24 hours after removal of the patches.

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Remarks:

5% peracetic acid solution, 3 min treatment

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

positive indication of irritation

Remarks:

5% peracetic acid solution, 3 min treatment

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Remarks:

5% peracetic acid solution, 3 min treatment

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

5% peracetic acid solution, 3 min treatment

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Remarks:

5% peracetic acid solution, 3 min treatment

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Remarks:

5% peracetic acid solution, 3 min treatment

Irritant / corrosive response data:

- Time of exposure: 3 minutes
Erythema: well defined, moderate and severe erythema, slight eschar formation; Edema: very slight to slight edema; Additional skin lesions: after one week all animals formed skin scales, which immediately peeled off; The irritation index is 3.3. At the end of the 14 day observation period the effects were completely reversible.
Therefore peroxyacetic acid 5 % is moderately irritating after an exposure time of 3 minutes.
- Time of exposure: 45 minutes
In depth necrosis and tissue loss (1-3 mm) at the application site. Erythema: moderate to severe erythema of the skin surrounding the application site; Edema: moderate to severe edema; Additional skin lesions: white and lateron green to yellow colouring of the skin, necrosis (all animals). Due to the severe effects the animals were killed on day 2.
Peroxyacetic acid 5 % has corrosive effects on the skin of the rabbit after a time of exposure of 45 minutes.

Other effects:

No systemic toxicity effects were observed.

Peroxyacetic acid 5 % was dermally applied to the rabbit to determine its primary cutaneous irritant properties. 0.5 mL of the test substance was given to the dorsal skin area of rabbits under occlusive conditions. The time of exposure was 3 and 45 minutes. General clinical signs were recorded and skin observations were performed 1, 24, 48 and 72 hours after patch removal in the 3 minutes group and 1 and 24 hours after patch removal in the 45 minutes group.

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

Peroxyacetic acid 5 % is moderately irritant if applied for 3 minutes and corrosive if applied for 45 minutes on the rabbit skin. There were no signs of systemic toxicity.
Classification: corrosive (causes burns)

Executive summary:

Peroxyacetic acid 5 % was dermally applied to the rabbit to determine its primary cutaneous irritant properties. 0.5 mL of the test substance was given to the dorsal skin area of rabbits under occlusive conditions. The time of exposure was 3 and 45 minutes. General clinical signs were recorded and skin observations were performed 1, 24, 48 and 72 hours after patch removal in the 3 minutes group and 1 and 24 hours after patch removal in the 45 minutes group.

 

In the 3 minutes group well defined, moderate to severe erythema, slight eschar formation and very slight to slight oedema were observed. An irritation index of 3.3 was established and the test material was considered to be moderately irritant after 3 minutes of exposure.

 

In the 45 minutes group moderate to severe erythema and oedema, discolouration of the skin and necrosis were observed. The test was terminated after 2 days due to severe effects. An irritation index was not established. The test material was considered to be corrosive after 45 minutes of exposure.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

other: White Russian albino

Details on test animals or test system and environmental conditions:

- Sex: females
- Number of animals per group: 3
- Age: 9-11 weeks
- Weight at study initiation: 2.5 – 3.0 kg
- Source: Asta-Werke AG, Bielefeld, Germany

Type of coverage:

occlusive

Preparation of test site:

other: clipped free of hair

Vehicle:

other: undiluted test substance

Controls:

other: Not applicable at the time of the study

Amount / concentration applied:

- Concentration: 15 %
- Application volume: 0.5 mL

Duration of treatment / exposure:

4 hour(s)

Observation period:

3-14 days post-exposure

Number of animals:

3

Details on study design:

- Controls: yes, an area of the skin was treated in the same way but without test substance
- The back of the animals was clipped free of hair between the scapulae and the sacrum (6.25 cm2). On both sides of the spinal column 2 test sites were assigned (a total of 4). 2 sites were left intact, 2 sites were abraded before application
- Removal of test substance: yes, after 4 hours the remaining test material was gently washed off
- Scoring system according to OECD guideline 404
- Examination time points: 1, 24, 48 and 72 hours after removal of the patches

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

All animals showed erythema and oedema of different severity on intact and abraded skin. Erythema persisted until day 14 on a constant and high level. The skin was blanched and brittle and tended to eschar formation. In the process of resolving scars were visible. Oedema formation was only transient and completely resolved by day 3. A number of observations are not considered in the Draize scoring system (colour changes, changes in skin consistency, elasticity etc.). They are however of importance for the evaluation of the skin damaging effects of a test substance. The test material is therefore considered to be corrosive to the rabbit skin.

Other effects:

There were no clinical signs of systemic toxicity.

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

The test material is considered to be corrosive to the rabbit skin.
Classification: corrosive (causes burns)

Executive summary:

The test material peracetic acid 15 % was applied to the intact and abraded skin of 3 rabbits in order to assess the skin irritating properties. The test material was used undiluted. The test sites were clipped and 2 of the 4 test sites were abraded. The test material was applied on a gauze pad and fixed onto the test sites under an occlusive wrap. 2 untreated test sites served as control. After 4 hours the patches were removed and the skin reactions were evaluated after 1, 24, 48 and 72 hours according to the Draize scoring system. Clinical signs were recorded.

 

All animals showed erythema and oedema of different severity on intact and abraded skin. Erythema persisted until day 14 on a constant and high level. The skin was blanched and brittle and tended to eschar formation. In the process of resolving scars were visible. Oedema formation was only transient and completely resolved by day 3. A number of observations are not considered in the Draize scoring system (colour changes, changes in skin consistency, elasticity etc.). They are however of importance for the evaluation of the skin damaging effects of a test substance. The test material is therefore considered to be corrosive to the rabbit skin.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

no guideline available

Principles of method if other than guideline:

Method: Draize Test
Exposure time 24 hours instead of 4 as recommended by OECD guideline 404.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

other: intact and abraded

Vehicle:

water

Controls:

no

Amount / concentration applied:

- Concentration: 3.4 %, 0.34 % and 0.034 % peracetic acid
- Application volume: 0.5 mL

Duration of treatment / exposure:

24 hour(s)

Observation period:

3 days

Number of animals:

2

Details on study design:

- Test substance was diluted at 1/10, 1/100 and 1/1000 (corresponding to 3.4 %, 0.34 % and 0.034 % peracetic acid)
- Test sites were left intact or scarified
- Scoring system: according to Food and Drug Administration; Draize, Woodard and Calvery; Draize
- Examination time points: 24, 48 and 72 hours
- After 72 hours, two rabbits were sacrificed and the skin was macroscopically and microscopically examined


SCORING SYSTEM:
∑24 hours + ∑72 hours for edema and erythema. The mean values for 24 hours and 72 hours are presented in the results section.

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: non-irritating

Remarks:

A 0.034% concentration was not irritating

Remarks on result:

no indication of irritation

Remarks:

0.034% peracetic acid, no individual edema score, but mean "overall irritation score" reported

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: non-irritating

Remarks:

A 0.034% concentration was not irritating

Remarks on result:

no indication of irritation

Remarks:

0.034% peracetic acid, no individual edema score, but mean "overall irritation score" reported

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: non-irritating

Remarks:

A 0.034% concentration was not irritating

Remarks on result:

no indication of irritation

Remarks:

0.034% peracetic acid, no individual erythema score, but mean "overall irritation score" reported

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: non-irritating

Remarks:

A 0.034% concentration was not irritating

Remarks on result:

no indication of irritation

Remarks:

0.034% peracetic acid, no individual erythema score, but mean "overall irritation score" reported

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24h/72h

Score:

1.6

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

0.34% peracetic acid, no individual edema score, but mean "overall irritation score" reported

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24h/72h

Score:

1.6

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

0.34% peracetic acid, no individual edema score, but mean "overall irritation score" reported

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24h/72h

Score:

1.6

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

0.34% peracetic acid, no individual erythema score, but mean "overall irritation score" reported

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24h/72h

Score:

1.6

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

0.34% peracetic acid, no individual erythema score, but mean "overall irritation score" reported

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24h/72h

Score:

5.7

Reversibility:

not reversible

Remarks:

A 3.4% peracetic acid concentration was corrosive

Remarks on result:

positive indication of irritation

Remarks:

3.4% peracetic acid, no individual edema score, but mean "overall irritation score" reported

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24h/72h

Score:

5.7

Reversibility:

not reversible

Remarks:

A 3.4% peracetic acid concentration was corrosive

Remarks on result:

positive indication of irritation

Remarks:

3.4% peracetic acid, no individual edema score, but mean "overall irritation score" reported

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24h/72h

Score:

5.7

Reversibility:

not reversible

Remarks:

A 3.4% peracetic acid concentration was corrosive

Remarks on result:

positive indication of irritation

Remarks:

3.4% peracetic acid, no individual erythema score, but mean "overall irritation score" reported

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24h/72h

Score:

5.7

Reversibility:

not reversible

Remarks:

A 3.4% peracetic acid concentration was corrosive

Remarks on result:

positive indication of irritation

Remarks:

3.4% peracetic acid, no individual erythema score, but mean "overall irritation score" reported

Irritant / corrosive response data:

- 3.4 % test solution: corrosive
- 0.34 % test solution: slightly irritating
- 0.17 % test solution: slightly irritating
- 0.034 % test solution: not irritating, no effect other than reversible enlargement of scars in scarified skin areas

Other effects:

No other observations reported.

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Remarks:

Non-irritating to corrosive, depending on the concentration topically applied to the skin of rabbits.

Conclusions:

Based on the results obtained, a 3.4 % peracetic acid solution is considered to be corrosive, while a 0.34 % dilution has slight irritating effects only; no skin irritating potential was evident with a 1/1000 dilution.

Executive summary:

The skin irritation potential of a 1/10, 1/100 and 1/1000 dilution of peracetic acid (3.4 %, 0.34 % and 0.034 %) was investigated in rabbits. Skin sites were examined macroscopically and microscopically.

 

The degree of skin reactions after dermal application of 0.5 mL of peracetic acid was concentration dependent. Eschar formation, necrosis and moderate edema was seen with the 1/10 dilution (3.4 % peracetic acid), while slight erythema and edema formation was evident with the 1/100 dilution (0.34 % peracetic acid); following topical application of a 1/1000 dilution (0.034 % peracetic acid), no skin reactions were evident. Microscopically, with the 1/10 dilution, necrosis of the dermis and epidermis was evident while with the 1/100 dilution, microscopic findings were not as pronounced as observed with the 1/10 dilution. Only slight local effects were notable with the 1/1000 dilution. Complete reversibility was observable only for the highest dilution, while scar formation was noted with the 1/10 dilution on days 23-25 of the study and on day 13 with the 1/100 dilution.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: EPA Toxic Substances Health Effects Test Guidelines (PB82-232984), Primary Eye Irritation

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: H.A.R.E., Hewitt, NJ, USA
- Sex: males and females
- Age: Young adult
- Weight: 2.28 – 2.36 kg (males), 2.05 – 2.53 kg (females)
- Number of animals per group: 3
- Controls: The left eyes served as controls

Vehicle:

other: the test material was dosed as received

Controls:

no

Amount / concentration applied:

- Concentration: 17 %
peracetic acid
- Application volume: 0.1 mL

Duration of treatment / exposure:

For 3 animals: Not applicable, eyes remained unwashed
For 3 animals: 20-30 seconds, eyes were washed thereafter with water.

Observation period (in vivo):

22 days

Number of animals or in vitro replicates:

6

Details on study design:

- Method of Administration: a volume of 0.1 mL test material was administered per test eye. The eyes of three of the rabbits were left unwashed while the eyes of the remaining three rabbits were gently washed with 100 mL of tap water 1 20-30 seconds after treatment
- Ophtalmoscopic examination: changes of the cornea, iris and conjunctiva
- Scoring system: Method of Draize - Observation period: observations were made at 1, 24, 48 and 72 hours and on day 4, 7, 10, 13 and 16 of the study

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Remarks:

Eye unwashed

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3.66

Max. score:

4

Reversibility:

not fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Remarks:

Eye unwashed

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Remarks:

Eye unwashed

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Remarks:

Eye unwashed

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Remarks:

Eye unwashed

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Remarks:

Eye unwashed

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Remarks:

Eye unwashed

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Remarks:

Eye unwashed

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Remarks:

Eye unwashed

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Remarks:

Eye unwashed

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Remarks:

Eye unwashed

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.66

Max. score:

4

Reversibility:

not fully reversible within: 16 days

Remarks on result:

positive indication of irritation

Remarks:

Eye unwashed

Irritant / corrosive response data:

Twenty-four hours after dosing, all eyes had dense corneal opacities, white conjunctivas, iritis and conjunctivitis. Washing the test eyes with tap water shortly after exposure did not significantly decrease the irritation observed.
The signs of irritation continued throughout the study as well as necrosis of the eyelids in all animals and a corneal eruption in one rabbit.

Other effects:

Diarrhoea (1 animal, day 7, died on day 8)

AVERAGE SCORE

Table 1: Individual scores 24 hours after end of treatment

Animal number	Cornea Opacity/Area	Iris Score	Conjunctiva			Other comments
			Redness	Chemosis	Discharge
1 M	4/4	2	0	1	2	Cw
2 M	3/4	2	0	1	3	Cw
3 M	3/4	2	0	2	2	Cw
4 F (w)	2/4	2	0	1	3	Cw
5 F (w)	3/4	2	0	2	3	Cw
6 F (w)	2/4	2	0	2	3	Cw

M= male

F= female

(w)= washed

Cw= conjunctiva - white

 

Table 2: Individual scores 48 hours after end of treatment

Animal number	Cornea Opacity/Area	Iris Score	Conjunctiva			Other comments
			Redness	Chemosis	Discharge
1 M	3/4	2	0	3	2	Cw
2 M	4/4	2	2	4	3	Cw
3 M	4/4	2	2	4	3	Cw
4 F (w)	3/4	2	0	4	3	Cw
5 F (w)	3/4	2	2	3	3	Cw
6 F (w)	4/4	2	1	4	3	Cw

M= male

F= female

(w)= washed

Cw= conjunctiva - white

 

Table 3: Individual scores 72 hours after end of treatment

Animal number	Cornea Opacity/Area	Iris Score	Conjunctiva			Other comments
			Redness	Chemosis	Discharge
1 M	4/4	2	0	3	2	Cw
2 M	4/4	2	0	4	3	Cw
3 M	4/4	2	0	4	3	Cw
4 F (w)	4/4	2	0	4	3	Cw
5 F (w)	4/4	2	0	4	3	Cw
6 F (w)	4/4	2	0	4	3	Cw

M= male

F= female

(w)= washed

Cw= conjunctiva - white

Interpretation of results:

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

Conclusions:

Under the conditions of this study, the test material is judged to be extremely irritating to both unwashed and washed eyes. In the light of the necrosis noted, the test material is considered to be corrosive to the eye.
Classification: risk of serious damage to eyes

Executive summary:

Dilute peracetic acid was instilled into the test eyes of six rabbits at a dose of 0.1 mL. The eyes of three of the rabbits were not washed while the eyes of the remaining three rabbits were gently washed with 100 mL of tap water approximately 20-30 seconds after treatment. Eyes were assessed for irritation using the method of Draize at 1, 24, 48 and 72 hours as well as day 4, 7, 10, 13 and 16 of the study. The study was terminated on day 22.

 

24 hours after dosing, all eyes had dense corneal opacities, white conjunctivas, irititis and conjunctivitis. These signs of irritation continued to be observed throughout the study as well as necrosis of the eyelids in all animals and a corneal eruption in one rabbit. By day 19 of the study, the eyes could no longer be scored due to fusion of the eyelids. The test was terminated on day 22 of the study. Washing the eyes shortly after application did not significantly reduce the irritating effect.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Hazleton Research Animals, Denver, PA, USA
- Sex: Males and females
- Age: Young adults
- Weight: 2.56 – 2.93 kg (males), 2.51 – 2.57 kg (females)
- Number of animals per group: 6 (3 per group)

Vehicle:

water

Controls:

no

Amount / concentration applied:

Concentration: 0.15 %
Amount applied: 0.1 mL

Duration of treatment / exposure:

Not applicable, eyes remained unwashed.

Observation period (in vivo):

4 days

Number of animals or in vitro replicates:

6

Details on study design:

- Controls: the left eyes served as controls
- Concentration of test substance: the test material was dosed as a 0.15 % use dilution in deionized water
- Ophtalmoscopic examination: changes of the cornea, iris and conjunctiva
- Other investigations: body weights
- Scoring system: Method of Draize
- Observation period: observations were made at 1, 24, 48 and 72 hours and on day 4 of the study

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 4 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 4 days

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of mild irritation

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Remarks on result:

probability of mild irritation

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Mild to moderate chemosis and severe discharge were noted in all eyes 1 hour post dosing. At the 24-hour scoring, slight corneal opacities, slight to mild redness and chemosis, and mild to severe discharge were noted in all eyes.
Irritation gradually resolved, and was completely resolved by study day 4.

Other effects:

None, body weight development within normal range. Initially severe discharge which had subsided by day 4 in all animals.

AVERAGE SCORE

Table 1: Individual scores 24 hours after end of treatment

Animal number	Cornea Opacity/Area	Iris Score	Conjunctiva			Cornea S/A
			Redness	Chemosis	Discharge
1 F	0/0	0	1	1	3	0/0
2 F	1/1	0	1	1	3	+/1
3 M	1/2	0	2	2	3	+/2
4 M	1/1	0	2	2	3	+/1
5 M	1/1	0	1	1	3	+/1
6 M	1/2	0	1	1	2	+/2

M= male

F= female

S/A= Stain/area

+ = fluorescein retention

 

Table 2: Individual scores 48 hours after end of treatment

Animal number	Cornea Opacity/Area	Iris Score	Conjunctiva			Cornea S/A
			Redness	Chemosis	Discharge
1 F	0/0	0	1	0	0	NA
2 F	0/0	0	1	0	1	0/0
3 M	1/1	0	1	0	1	+/1
4 M	0/0	0	2	1	1	0/0
5 M	0/0	0	1	1	2	0/0
6 M	1/2	0	2	1	1	+/2

M= male

F= female

S/A= Stain/area

+ = fluorescein retention

 

Table 3: Individual scores 72 hours after end of treatment

Animal number	Cornea Opacity/Area	Iris Score	Conjunctiva			Cornea S/A
			Redness	Chemosis	Discharge
1 F	0/0	0	0	0	0	NA
2 F	0/0	0	0	0	0	NA
3 M	0/0	0	0	0	0	0/0
4 M	0/0	0	1	0	0	NA
5 M	0/0	0	0	0	0	NA
6 M	1/1	0	1	0	1	+/1

M= male

F= female

S/A= Stain/area

+ = fluorescein retention

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Under the conditions of the study the test material is considered to be mildly irritating.
Classification: slightly irritating

Executive summary:

Peracetic acid 0.15 % use dilution was instilled into the test eyes of six rabbits at a dose of 0.1 mL. Each eye was held closed for approximately one second after administration. Eyes were assessed for irritation at 1, 24, 48 and 72 hours as well as day 4.

 

Mild to moderate chemosis and severe discharge were noted in all eyes 1 hours post dosing. At the 24-hour scoring, slight corneal opacities, slight to moderate redness and chemosis and mild to severe discharge were noted in all eyes. Irritation gradually resolved and was completely resolved by study day 4.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin

 

The skin irritation potential of peracetic acid has been investigated in the rabbit by testing dilutions of equilibrium solutions of peracetic acid containing about 0.2 to > 35% of peracetic acid.

 

The results demonstrate that peracetic acid at actual topical concentrations of less than 1% is neither irritating nor corrosive to skin, while peracetic acid at concentrations of 3% and higher causes burns or severe burns of the skin (Duprat, 1974; Mayer, 1988; Zechel, 1988). When tested at concentrations up to 0.34% peracetic acid in the equilibrium mixture are not or only slightly irritating (Duprat et al., 1974). At peracetic acid concentrations between 3% and 5% in the equilibrium mixture, the results of the studies of Duprat et al. (1974) and Janssen et al. (1987) revealed destruction of the skin was noted later than 1 hour after administration. In the study of Mayer (1988), corrosion of the skin was noted 45 minutes after application of an equilibrium mixture containing 5% of while with a concentration of 10% peracetic acid in the equilibrium mixture, skin corrosion was reported 3 minutes after application (Zechel, 1988).

 

In addition to the animal studies, there are publications on the use of peracetic acid as disinfection agent available where the irritating potential of peracetic acidin solution were evaluated.

 

In one publication, the cytotoxic and irritating potential of peracetic acid in humans with a view to its local tolerance when used as a disinfectant for hand washing procedures applied by surgeons was investigated (Kramer, 1987). The material tested was a Wofasteril product containing 0.5 % of peracetic acid. In this small but representative collective of surgeons, 3 of 15 surgeons developed immediately erythema and 6 of 15 surgeons developed dermatosis of the hands after 7 days following daily soaping, brushing and disinfection of skin with peracetic acid at a concentration of 0.5 %. The investigations performed demonstrated that peracetic acid applied as Wofasteril caused dermal irritation reactions in a third of health care workers.

 

In another publication a Patch test (48 h, occlusive) was carried out with peracetic acid in a product, which was tested in dilutions of 1:33 (1500 mg/L peracetic acid), 1:20 (2500 mg/L peracetic acid) and 1:15 (correct value should be 3300 mg/L). Based on the results it was concluded that up to 2500 mg/L peracetic acid (corresponding to an about 0.25 % solution) is non irritating. At 3300 mg/L peracetic acid (corresponding to an about 0.33 % solution) is a mild irritant (French, 1993).

 

Kretschmer et al. (1971) described the effects of diluted peracetic acid solutions used as an aerosol (0.8 % peracetic acid), as a disinfectant for human skin (0.08 or 0.2 % peracetic acid) and for the treatment of a recurrent, pruritic epidermitis (0.1 % peracetic acid).

 

As a consequence of the overall data on skin irritation and corrosion, the peracetic acid is classified for skin corrosion. 

 

 

Eye

 

The results of studies on the potential eye irritation/corrosion demonstrated that at higher peracetic acid concentrations, all formulations caused severe and irreversible damage to the rabbit eye leading to a classification and labelling as a severe eye irritant. Highly diluted formulations exerted only mildly irritating effects which were demonstrated to be completely reversible.

 

In a study performed according to GLP and OECD guideline 405 peracetic acid at 0.15 % use dilution was instilled into the test eyes of six rabbits at a dose of 0.1 mL (Freeman, 1991). Each eye was held closed for approximately one second after administration. The eyes were then assessed for irritation at 1, 24, 48 and 72 hours as well as day 4, respectively. Mild to moderate chemosis and severe discharge were noted in all eyes 1 hours post dosing. At the 24-hour scoring, slight corneal opacities, slight to moderate redness and chemosis and mild to severe discharge were noted in all eyes. The slight irritation gradually resolved and was completely resolved by study day 4.

 

However, at concentrations of ≥3%, peracetic acid has been demonstrated to be corrosive to the skin which in parallel qualifies for a classification into category 1 for eye damage according the GHS classification system. This is supported by the results of the eye irritation study where application of a 17% peracetic acid led to corrosive effects (Cascieri, 1983).

 

As a consequence, the eye irritation/corrosion potential identified in various studies is reflected in a classification for eye damage.

 

 

Effects on skin irritation/corrosion: corrosive

 

Effects on eye irritation: corrosive

 

Effects on respiratory irritation: irritating

Justification for classification or non-classification

The available data on skin and eye irritation/corrosion of peracetic acid meet the criteria for classification, resulting in classification for skin corrosion (category 1A) and eye damage (category 1), according to EU Regulation (EC) No 1272/2008 (CLP), as amended for the seventeenth time in Regulation (EU) 2021/849.