Pyridine-2-thiol 1-oxide, sodium salt

Endpoint summary

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