Pyrithione zinc

Carcinogenicity

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Dose descriptor:

NOAEL

0.5 mg/kg bw/day

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.

Available studies are presented in Tables 5.12 and 5.13 below. Studies have been carried out in the rat and the mouse. Further studies were not carried out in dogs because of the known effect of Pyrithiones on the tapetum of the dog which results in blindness in the dog, seeDelahunt, C.S., Stebbins, R.B., Anderson, J., and Bailey, J. (1962).andCloyd, G.G., Wyman, M., Shadduck, JA. (1978).

In an old and shortly reported non-guideline study with rat,Larson (1958), Zinc pyrithione had no carcinogenic potential to rat with the used doses.

Nonetheless, in studies with Sodium Omadine, with oral sampling with rat and dermal sampling with mouse, also no evidence of tumourigenic potential was identified.

A GLP study to GuidelineUS EPA 83-2, which complies with OECD 453.byHusband (1991),investigated the oral (gavage) administration of Sodium Pyrithione to rats over 104 weeks. This study constituted a combined carcinogenicity / chronic toxicity study.

An NOEL of 0.5 mg/kg bw/day was established in the study.

A GLP study to GuidelineUS EPA 83-2, which complies with OECD 453.byHusband (1991), investigated the DERMAL oral (gavage) administration of Sodium Pyrithione to the mouse over 80 weeks. This study constituted a combined carcinogenicity / chronic toxicity study.

An NOEL of 0.5 mg/kg bw/day was established in the study.

A GLP study to GuidelineUS EPA OPPTS 870.4300 which complies with OCED 453,byCivalese et al (2004),investigated the oral (gavage) administration of sodium pyrithione to rats over 104 weeks. This study constituted a combined carcinogenicity / chronic toxicity study.

An NOAEL for both sexes can be considered to be 0.5 mg/kg/day.

In a non-GLP study conducted byLarson (1958),60 male and 60 female rats were exposed to zinc pyrithione in the diet at 0, 2, 5, 10, 25, and 50 ppm for 2 years. 

The NOAEL for this study was 10 ppm (0.5 mg/kg/day)based on a reduced survivability in female animals at 25 ppm and hind limb weakness at 25 and 50 ppm. Male rats were observed to have a decrease in body weight at 50 ppm.

1.1.1.1         Carcinogenicity: oral

Table 5.12: Summary of carcinogenicity via the oral route

Method	Results	Remarks	Reference
US EPA 83-2, which complies with OECD 453. GLP Oral(gavage) Rat Crl: CD (SD) (VAF Plus) 50 per sex per dose. 0, 0.5, 1.5 and 3.5 mg/kg bw/day Duration: 2 years	LO(A)EL – 1.5 mg/kg bw/day NO(A)EL – 0.5 mg/kg bw/day Sodium Omadine did not affect tumour formation adversely. Decreases in body weight gain, hind limb muscle atrophy and histopathological changes in skeletal muscle, spinal cord and in the eyes were observed in the high dose group. Some, but not all of these effects were observed to a lesser degree in the mid dose group.	Reliability – 1 Purpose flag Study result type Test material: Sodium Omadine, 41.2% aqueous dispersion	Husband RFA, Newman AJ and Lee PN (1991) (unpublished)
US EPA 83-2, which complies with OECD 453. GLP Oral(gavage) Rat Duration: 2 years	NO(A)EL – 0.5 mg/kg bw/day Signs of toxicity, such as, ataxia, decreased muscle tone and emaciation were seen in animals of both sexes. In addition, a lower body weight was noted in low and high-dose males and in mid- and high- dose females when compared to controls. There were no incidences of neoplasia with sodium pyrithione up to 2.8 mg/kg/day.	Reliability – 1 Purpose flag Study result type Test material: Sodium Pyrithione	Key study Cicalese R, Argentino-Storino A, (2004) (unpublished)
No specific guideline. Oral, Rat strain not stated 10 per sex per dose.0, 2, 5, 10, 25 and 50 ppm in diet (about 0.2, 0.5, 1.0, 2.5 and 5.0 mg/kg bw/day)   Duration: 2 years	LO(A)EL – Females 25 ppm Males 50 ppm NO(A)EL – 10 ppm (0.5 mg/kg/day) In male rats, no effects were noted on survival, whereas in female rats with 25 and 50 ppm diets, numbers of survived animals decreased. Death was commonly preceded by the development of hind limb paralysis.	Reliability – 1 Purpose flag Study result type Test material: Zn Pyrithione, purity not stated.	Larson PS (1958) (unpublished)

1.1.1.2         Carcinogenicity: inhalation

This information is not available.

1.1.1.3         Carcinogenicity: dermal

Table 5.13: Summary of carcinogenicity via the dermal route

Method	Results	Remarks	Reference
US EPA 83-2, which complies with OECD 453. GLP Dermal, Mouse Crl: CD-1 (ICR) BR (VAF Plus) 50 per sex per dose.0, 5, 15 and 40 mg/kg bw/day Duration: 80 weeks	LO(A)EL - 15 mg/kg bw/day NO(A)EL – 5 mg/kg bw/day Sodium Omadine did not affect tumour formation adversely. The only observed lesion, which appeared to be related to the treatment, was epidermal hyperplasia at the application sites of high and mid dose animals.	Reliability – 1 Purpose flag Study result type Test material: Sodium pyrithione 41.2% aqueous dispersion.	Husband RFA, Newman AJ and Lee PN (1991) (unpublished)