Pyridine-2-thiol 1-oxide, sodium salt

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - dermal (%):

0.41

Additional information

A GLP study carried out according to US EPA Guideline 85-1 by Chadwick et al, 1989, [reference 7.1.1.002, EZPTF 6021-002]investigated the disposition and metabolism of Sodium Omadine in rats after oral and intravenous administration.The results with sodium pyrithione indicated that the pyrithione moiety is responsible for the toxicity regardless of the salt.

 

Based on comparison of urinary and faecal excretion in the i.v. and p.o. dosed groups, it was shown that sodium Pyrithione was well absorbed by males and females in all three oral dose groups. Metabolism was extensive. The major urinary metabolite was 2‑pyridinethiol-1-oxide-S-glucuronide (designated metabolite K), which is the glucuronic acid conjugate of free pyrithione. Metabolite K represented 59-67% of the dose in 0-72 hour urine after a single 0.5 mg/Kg oral dose, 41-49% after multiple 0.5 mg/Kg oral doses, 50% after a single 0.5 mg/Kg i.v. dose, and 43-47% after a single 25 mg/Kg oral dose. No unconjugated pyrithione was detected. 

After oral dosing, the concentration of¹⁴C pyrithione equivalents in the blood showed a broad secondary peak after the initial peak following dosing. Evidence of a secondary peak or plateau was also seen after i.v. dosing. Elimination from the blood occurred at several rates, with a slow terminal rate in all of the orally dosed groups. No abnormalities were observed in any of the treatment groups.

In addition, a non-GLP study by Adams et al, 1996 [reference 7.1.1.003, EZPTF 6021 -005] was completed to investigate the acute toxicity, excretion, metabolism, and tissue distribution of radiolabeled sodium pyrithione, zinc pyrithione, and Omadine MDS following intravenous administration in pigs.

The urinary clearance of sodium pyrithione was much more rapid and complete than zinc pyrithione and Omadine MDS. After 96 hours, 94.6% of the sodium pyrithione was excreted through the urine compared to 50.8% of zinc pyrithione and 56.4% of Omadine MDS. 96 hours after administration the residual tissue radioactivity reflected the more rapid excretory rate observed with sodium pyrithione. In this study the primary urinary metabolite was disulfide pyrithione.

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.

Discussion on absorption rate:

Dermal penetration rates have been determined from the study ESPTF 6021-009 (reference 7.1.2.001).

 

In this study,¹⁴C-NaPT in aqueous solution was administered dermally to 2 groups of male rats at 1 or 25 mg/kg, with exposures being of 6 hr. Absorbed and unabsorbed radioactivity was determined at 48 hr after application of labeled NaPT. The extent of systemic absorption of labeled NaPT, determined as the sum of the percentages of¹⁴C-NaPT derived in urine and feces over 48 hr and in tissues and carcass at 48 hr, was 8% at 1 mg/kgand at 25 mg/kg the fraction absorbed decreased to 2%. 

 

For the risk assessments, the value of 8% is used.

In another Wedig et al study, 1978 [reference 7.1.2.002, EZPTF 6021 -007] metabolites were identified from urine of pigs dosed either dermally or intravenously with rabiolabeled zinc pyrithione, radiolabeled sodium pyrithione, or radiolabeled Omadine MDS.

For all test substances, the major metabolites after dosing dermally were: 2,2'-pyridyldisulfide and 2 -pyridyl-N-oxide sulfonic acid.

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.