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Carcinogenicity

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Description of key information

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
NOAEL
0.5 mg/kg bw/day

Carcinogenicity: via dermal route

Endpoint conclusion
Dose descriptor:
NOAEL
5 mg/kg bw/day

Additional information

Available studies are presented in Table 7.7.1 below. Studies have been carried out in the rat and the mouse.

 

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

 

A GLP study to Guideline US EPA 83-2, which complies with OECD 453. by Husband (1991),[reference 7.7.002, EZPTF 6051-001], investigated the oral (gavage) administration of Sodium Pyrithione to rats over 104 weeks. This study constituted a combined carcinogenicity / chronic toxicity study.

 

Sodium Pyrithione 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.

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

 

A GLP study to Guideline US EPA 83-2, which complies with OECD 453. by Husband (1991), [reference 7.7.001, EZPTF 6071-001], investigated the DERMAL) administration of Sodium Pyrithione to the mouse over 80 weeks. This study constituted a carcinogenicity study.

 

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.

An NOEL of 5.0 mg/kg bw/day was established in the study.

 

A GLP study to Guideline US EPA OPPTS 870.4300 which complies with OCED 453,by Civalese et al (2004), [reference 7.7.003, EZPTF 6051-002], investigated the oral (gavage) administration of Sodium Pyrithione to rats over 104 weeks. This study constituted a combined carcinogenicity / chronic toxicity study.

 

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.

 

Low dose males were sacrificed on week 97 due to the high mortality observed compared to controls and mortality of the mid- and high-dose females (1.5, 2.1 mg/kg/day) was higher than controls. However, there were no indications of significant different incidences of predominant pathology between control and treated animals.

There were no incidences of neoplasia with sodium Pyrithione up to 2.8 mg/kg/day.

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


Table 7.7.1        Summary of chronic toxicity/carcinogenicity

Route

Duration

Species
Strain
Sex
no/group

Dose levels
[mg/kg bw/day]
frequency of application

Results

LO(A)EL

NO(A)EL

Reference

[mg/kg bw/day]

Oral (gavage)

2 years

Rat

Crl: CD (SD) (VAF Plus) 50 per sex per dose

US EPA 83-2, which complies with OECD 453. GLP

0, 0.5, 1.5 and 3.5 mg/kg bw/day

 

Test material: Sodium Omadine®, 41.2% aqueous dispersion.

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.

1.5 mg/kg bw/day

0.5 mg/kg bw/day

7.7.002

 

EZPTF 6051-001

 

Husband RFA, Newman AJ and Lee PN (1991)

(unpublished)

Oral (gavage)

2 years

Rat

US EPA 83-2, which complies with OECD 453. GLP

 

Test material:

Natrium Pyrion

40 % LSG.

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.Low dose males were sacrificed on week 97 due to the high mortality observed compared to controls and mortality of the mid- and high-dose females (1.5, 2.1 mg/kg/day) was higher than controls. However, there were no indications of significant different incidences of predominant pathology between control and treated animals.

 

There were no incidences of neoplasia with sodium Pyrithione up to 2.8 mg/kg/day.

 

There were treatment related degenerative changes of the sciatic nerve and skeletal muscle in all treatment groups and gastric reactive change at 2.8 mg/kg/day in male rats only.

 

0.5 mg /kg bw/day

Key study

7.7.003

 

EZPTF 6051-002

 

Cicalese R, Argentino-Storino A, (2004)

(unpublished)

Dermal

80 weeks

Mouse

Crl: CD-1 (ICR) BR (VAF Plus)

50 per sex per dose

US EPA 83-2, which complies with OECD 453. GLP

0, 5, 15 and 40 mg/kg bw/day

Test material: Sodium Omadine®, 41.2% aqueous dispersion.

 

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.

15 mg/kg bw/day

5 mg/kg bw/day

7.7.001

 

EZPTF 6071-001

 

Husband RFA, Newman AJ and Lee PN (1991)

(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.

Justification for classification or non-classification