Pyrithione zinc

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Dose descriptor:

LD50

Value:

221 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

1.03 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

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.

Acute toxicity: oral

Three acute oral toxicity data studies (see Table 5.1 below) indicate that zinc pyrithione has an LD50 = 221 mg/kg and therefore meets the criteria for classification as:-

DSD:  Harmful, R22 Harmful if swallowed.

CLP:   Acute Tox 4; H332

 

Table 5.1: Summary of acute oral toxicity

Method	Results	Remarks	Reference
Complied with OECD 401. GLP (self certification by the laboratory) Oral, Rat Wistar Albino, 5 per sex group,	Males 302 mg/kg bw, females 221 mg/kg bw and combined 269 mg/kg bw. Clinical signs noted included piloerection, lethargy, ptosis and diarrhoea.	Reliability – 1 Purpose flag Study result type  48% dispersion of Zinc pyrithione.	Key study Cerven DR (1986) (unpublished)
OECD 401. GLP (self certification by the laboratory) Oral, Rat, Sprague-Dawley CD.	Females 774 mg/kg bw. Clinical signs of systemic toxicity, ataxia, dieresis, hunched posture, lethargy, decreased respiratory rate in all dosed groups. Diarrhoea, laboured respiration, red/brown stains around the eyes or snout, piloerection, ptosis and splayed or tiptoe gait in females.	Reliability – 1 Purpose flag Study report type Zinc Pyrithione powder	Allen DJ (1997) (unpublished)

Acute toxicity: inhalation

Three different inhalation toxicity studies and results are available (see Table 5.2 below).

The lowest LC50, 0.14 mg/l/4 h was received by whole body exposure to zinc pyrithione dispersion-Ulrich (1991).

 Some oral ingestion of test material is possible due to preening of contaminated fur, which may have effect on the result in the whole body study. Nose-only studies are considered more relevant.

In a nose-only limit study ,Ulrich (19991), with micronized powder 3/10 animals died at dose 0.61 mg/l/4h indicating LC50 of less than 1 mg/l. 

One animal (1 male out of 5 and 0 females out 5) out of ten died following 4 hour exposure via nose-only to 0.24 mg/L of ZPT. At 0.61 mg/L of ZPT 3 out of 10 animals (1 male and 2 female animals) died following 4 hours of exposure via nose-only. This study was carried out for the USEPA FIFRA registration and based on the interest of sparing animals and the fact that the data suggested that the LC₅₀for ZPT following four hours of nose-only exposures would be >0.61 but less than 2.0 mg/L the classification of “Harmful if Inhaled” Category IIIwas voluntarily accepted.  This study stopped short in identifying the arithmetic LC₅₀as the data indicated that the LC₅₀would be clearly under 2.0 mg/L but greater than 0.61 mg/L (classification scheme for USEPA FIFRA). Based on this fact the study is unacceptable in setting an LC₅₀value. 

Subsequent to this study a guideline study has been carried that identified the inhalation LC₅₀for ZPT to be 1.03 mg/l (see below)

In a further GLP compliant nose only study,Blagden (1996),carried out to OECD 403,3 groups of 10 Sprague-Dawley rats (5 males and 5 females) were exposed to a dust atmosphere at concentrations of 1.82, 0.95 and 0.53 mg/L. The animals were exposed for up 4 hours using a nose only exposure system. Mortality was noted in all groups on Day 1 after exposure. At clinical observations abnormal findings were noted during the study in all dosed groups. Majority of surviving animals recovered to appear normal 2 - 8 days after exposure. In the first week after dosing incidents of bodyweight loss and reduced bodyweight gain was noted in surviving animals. With the exception of one female, normal bodyweight development was noted during the second week. Necropsy of the animals that died or were killed moribund showed lung abnormalities and liver changes. With the exception of one female exposed to 0.53 mg/L (dark foci on the lungs) no abnormalities were detected in the animals killed at study termination.

LC₅₀determinations were 1.03 (0.74 - 1.43) mg/L for males + females combined (males 0.84 (0.54 - 1.31) mg/L ; females 1.34 (0.66 - 2.73) mg/L)

Table 5.2: Summary of acute inhalation toxicity
Method	Results	Remarks	Reference
OECD 403. GLP (self certification by the laboratory) Inhalation(nose only) Rat Sprague-Dawley CD albino, 5 per sex group.	1.03 mg/1/4 h (males 0.84 mg/l,females 1.34 mg/l) Clinical signs were common abnormalities like wet fur, hunched posture, pilo-erection, decreased respiratory rate, pallor of the extremities and ptosis, incidents of lethargy, ataxia, laboured gasping and noisy respiration, red/brown staining around the eyes, snout and mouth. Occasional or isolated incidents of increased respiratory rate, sneezing, dehydration, increased salivation and an apparent stiffness in the hind legs. Majority of surviving animals recovered to appear normal 2 – 8 days after exposure..	Reliability – 1 Purpose flag Study result type Zinc Pyrithione powder, purity not specified	Key study Blagden SM (1996) (unpublished)
US EPA 81-3, which complied with OECD 403. GLP (self certification by the laboratory) Inhalation(whole body) Rat Sprague-Dawley CD albino 5 per sex group.	0.14 mg/1/4h (95% confidence limits 0.1–0.2 mg/l). Deaths occurred at all exposure levels mainly on day 1 exposure. Clinical effects included prostration, gasping, laboured breathing, trembling and hunched posture.	Reliability – 1 Purpose flag Study result type Zinc Omadine FPS 48% (analysed 52.4%) (the test material suspension was diluted with water)	Ulrich CE (1991) (unpublished)
US EPA 81-3, which complied with OECD 403. GLP (self certification by the laboratory) Inhalation(nose only) Rat Sprague-Dawley CD albino, 5 sex per group.	>0.61 mg/1/4h (not a true LC50 value)	Reliability – 1 Purpose flag Study report type Zinc pyrithione powder 96% (micronized)	Ulrich CE (1991) (unpublished)

Based on the data above Zinc pyrithione is classified as:-

DSD: Toxic, R23 Toxic by inhalation.

CLP:   Toxic, Acute tox cat 3, H331 Fatal if inhaled

         

Acute toxicity: dermal

Acute dermal toxicity studies (see Table 5.3 below) have been carried out in both rats and rabbits. These studies indicate that the dermal route of exposure warrants no classification.

In a study conducted byCerven, D.R., (1991), one animal died on Day 2 after exposure to 2,000 mg/kg. 

The LD₅₀is greater than 2000 mg/kg of body weight. In accordance with the provision of Council Directive 67/548/EEC, classification is not required.

Allen DJ (1997)conducted a GLP study under US EPA FIFRA Section 81-2: Acute Dermal Toxicity Study 1984 guidelines. The Dermal LD₅₀: > 2000 mg/kg.

Table 5.3: Summary of acute dermal toxicity

Method	Results	Remarks	Reference
US EPA 81-2, which complies with OECD 402. GLP (self certification by the laboratory) Dermal, Rat Sprague-Dawley CD, 5 per sex.	14 days post exposure >2000 mg/kg bw   No signs of systemic toxicity or skin irritation were noted during the study.	Reliability -1 Purpose flag Study result type Zinc Omadine powder, >97%	Key study Allen DJ (1997) (unpublished)
US EPA 81-2, which complies with OECD 402. GLP (self certification by the laboratory) Dermal, Rabbit New Zealand Albino. 5 per sex.	14 days post exposure period >2000 mg/kg bw	Reliability – 1 Purpose flag Study result type Zinc Omadine powder, >97%	Cerven DR (1991) (unpublished)