Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

7.3.1  Dermal irritation/Corrosion

In a GLP compliant acute dermal irritation / corrosion test in rabbits according to OECD 404, 1992
Directive 92/69/EEC, B.4.conducted by Wolf
 (2001)[reference 7.3.1.001, ESPTF 6014-001], the following observation were made:

 

In 2/3 animals severe erythema were noted. Eschar was formed subsequently but finally desquamated and skin was normal again at the end of the observation period. In all animals oedema were noted already after the patch removal. Whereas 1/3 animals was free from oedema from 24 h p.a. onwards, oedema in different grades of severity were noted in the other two animals until 6 or 10 days p.a. Skin lesions at the application sites were reversible within 14 days p.a.

 

According to the EU classification criteria sodium pyrithione is irritating to the skin.

 

In a further GLP compliant study in rabbits by Cerven (1987) [reference 7.3.1.002, ESPTF 6014-002], which complies with US EPA FIFRA Series 81-5, similar to OECD 404, 1992 Directive 92/69/EEC, B.4., the following observations were made:

 

Erythema was absent to slight at 5, 24, 48, and 72 hours and oedema was absent to slight at 5, 24, 48, and 72 hours.

 

According to the EU classification criteria sodium pyrithione is irritating to the skin

 

Accordingly,sodium pyrithione meets the criteria for classification (Annex VI to Council Directive 67/548/EEC) as irritant to skin and should therefore be designated with risk phrase R38 (Irritating to skin.).

7.3.2  Eye irritation

Three studies have been performed.

 

In a GLP study with rabbits to US EPA FIFRA 40 CFR 158, Guideline Reference #81-4; OECD 405, 1987 Directive 92/69/EEC, B.5.[reference 7.3.2.001, ESPTF 6014-003 ], Cerven (1996) identified the following effects:

There was no corneal opacity noted at any observation period.
 Iritis, noted in 6/6 eyes, cleared by Day2. Conjuctival irritation, noted in 6/6 eyes, cleared by Day 14.

 

Three animals died by Day 2 with predeath signs of lethargy, prostration, soiling of the anogenital area, convulsions, tachypnea, ataxia, and wetness of the nose/mouth area. Physical signs noted in survivors included lethargy, yellow nasal discharge, and yellow staining of the nose/mouth area.

 

Necropsy of the animals that died during the study revealed abnormalities of the lungs, peritoneal cavity, and gastrointestinal tract, as well as wetness of the nose/mouth area and yellow nasal discharge.

 

The test article produced irritation which cleared within 14 days. However, the physical signs and mortality produced by the application indicates that the material is toxic to rabbits via this route.

 

The substance is classified as irritating and assigned the risk phrase R36 Irritating to eyes.

 

In a further GLP study with rabbits conducted to US EPA FIFRA 40 CFR 158, Guideline Reference #81-4; OECD 405, 1987 Directive 92/69/EEC, B.5.[reference 7.3.2.004, ESPTF 6014-004 ], Cerven (1998) identified the following effects:

 

Two animals died by Day 2 with predeath signs of convulsions, prostration, shallow breathing, wetness of the nose/mouth area, and abnormal posture. Three of the four surviving animals appeared normal during the observation period. Wetness of the nose/mouth area and yellow nasal discharge were noted in survivors. Corneal opacity was noted in one eye on Day 1, but cleared by Day 2. Iritis was noted in two eyes on Day 1. Conjuctival irritation was noted in six eyes, but cleared by Day 3 in the surviving animals.

 

The test article produced corneal opacity and irritation which cleared by Day 3. However, the clinical signs and toxicity produced by this application indicates that the material is toxic to rabbits via this route.

 

The substance is classified as irritating and assigned the risk phrase R36 Irritating to eyes.

Since toxic effects by this route of administration were noted it was felt necessary that further identification of the potential impact upon humans should be investigated. A further study was undertaken using monkeys.

  

In a further GLP study with Cynomolgus monkeys conducted to US EPA FIFRA 40 CFR 158, Guideline Reference #81-4; OECD 405, 1987 Directive 92/69/EEC, B.5. [reference 7.3.2.003, ESPTF 6014-005 ], Nass (1997) identified the following effects:

 

There were no deaths, clinical findings or remarkable changes in body weights during the study period. The Maximum Average Score was 2.0 at 48 hours post-instillation. A positive conjuctival reaction was noted in the treated eye of one male animal. Minor conjuctival irritation was observed for the other male while no ocular irritation was noted for the female. There were no corneal or iridial findings. All irritation was reversible and completely subsided by Day 7. No signs of systemic toxicity were observed.

 

The test article produced reversible irritation which cleared within 7 days. No signs of systemic toxicity were observed.

 

The above data indicates thatsodium pyrithione meets the criteria for classification (Annex VI to Council Directive 67/548/EEC) as irritant to eyes and should therefore be designated with risk phrase R36 (Irritating to eyes.).

Table 7.3.1     Summary of skin irritation

Species

Method
Guideline

Average score

24, 48, 72 h

Reversibility

Result

Reference

Erythema

Oedema

Rabbit,

New Zealand

Albino,

3 females

 

OECD 404, 1992
Directive 92/69/EEC, B.4.

GLP (self certification by the laboratory).

The test material was Sodium Pyrion powder (>92.5%)

1.9

1.7

Yes

Irritating to skin

Key Study

7.3.1.001

ESPTF 6014-001

 

Wolf T (2001).

(unpublished)

Rabbit,

New Zealand

Albino,

6 animals

 

US EPA FIFRA Series 81-5, similar to OECD 404, 1992
Directive 92/69/EEC, B.4.

GLP (self certification by the laboratory)

Test material 40% sodium pyrithione aqueous solution

0.8

0.17

Yes

Irritating to skin

7.3.1.002

 

ESPTF 6014-002

 

Cerven DR (1987)

(unpublished)

Table 7.3.2          Summary of eye irritation

Species

Method

Average score 24, 48, 72 h

Reversibility

Result

Reference

Cornea

Iris

Conjunctiva

Red-ness

Chemosis

Rabbit, New Zealand , 6 females

US EPA FIFRA 40 CFR 158, Guideline Reference #81-4; OECD 405, 1987
Directive 92/69/EEC, B.5.

GLP (self certification

by the laboratory)

Sodium Omadine 40% aqueous solution

 

0.0

 

 

1.0

 

 

2.1

1.4

Yes

The test article produced irritation which cleared within 14 days. However, the physical signs and mortality produced by the application indicates that the material is toxic to rabbits via this route.

7.3.2.001

 

ESPTF 6014-003

 

Cerven DR (1996)

 

(unpublished)

 

Rabbit, New Zealand , 6 females

US EPA FIFRA 40 CFR 158, Guideline Reference #81-4; OECD 405, 1987
Directive 92/69/EEC, B.5.

GLP (self certification

by the laboratory)

Sodium Omadine 40% aqueous solution

 

0.1

0.1

0.9

0.5

Yes

The test article produced corneal opacity and irritation which cleared by Day 3. However, the clinical signs and toxicity produced by this application indicates that the material is toxic to rabbits via this route.

7.3.2.004

 

ESPTF 6014-004

 

Cerven DR (1996)

 

(unpublished)

 

Cynomolgus monkey, 2 male, 1 female

OECD 405. GLP (self certification by the laboratory).

 

The test material was 0.1 ml Zinc Pyrion powder (97.9%)

0.0

0.0

0.7

0.0

Yes

The Maximum Average Score was 2.0 at 48 hours post-instillation. A positive conjuctival reaction was noted in the treated eye of one male animal. Minor conjuctival irritation was observed for the other male while no ocular irritation was noted for the female. There were no corneal or iridial findings. All irritation was reversible and completely subsided by Day 7. No signs of systemic toxicity were observed.

Key Study

 

7.3.2.003

 

EZPTF 6014-005

 

Nass D (1997)

 

(unpublished)

The information contained within this robust summary document comes from studies which are in the ownership of Arch Chemicals Inc. and which are protected in several regions globally. This information may not be used for any purpose other than in support of the Chemical safety Report submitted by Arch Chemicals Inc. under RegulationEC 1907/2006.


Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification