Pyridine-2-thiol 1-oxide, sodium salt

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.7600 (Dermal Penetration)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pyridine-2-thiol 1-oxide, sodium salt

EC Number:

223-296-5

EC Name:

Pyridine-2-thiol 1-oxide, sodium salt

Cas Number:

3811-73-2

Molecular formula:

C5H5NOS.Na

IUPAC Name:

sodium (1-oxo-1λ⁵-pyridin-2-yl)sulfanide

Details on test material:

- Analytical purity: 41.4%
- Lot/batch No.: S08708
- Radiochemical purity (if radiolabelling): 99.1%
- Specific activity (if radiolabelling): 3.25 and 886.76 uCi/mg for 1 and 25 mg/kg respectively

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

-Source: Taconic Farms
-Age: 7-8weeks
-Weight: 271-299g

Administration / exposure

Type of coverage:

open

Vehicle:

water

Duration of exposure:

6h

Doses:

-Dose: 1mg/kg (2.5 mg/ml) or 25mg/kg (62.5 mg/ml)
-Appliation site size: 10 cm sq

No. of animals per group:

5

Details on study design:

-Sampling times: 6, 12, 24 and 48 hour for urine and feces; 48 hours after application for tissues and carcass.
-Samples: Urine, faeces, organs, carcass, skin with substance not removed, liquid used for washing the skin, and protective appliances

Results and discussion

Signs and symptoms of toxicity:

no effects

Dermal irritation:

no effects

Absorption in different matrices:

1.0 mg of NaPT/kg of bodyweight – 8.0% absorbed
25 mg of NaPT/kg of bodyweight – 2.0% absorbed

Total recovery:

68.3 ± 7.8% at 1.0 mg/kg
77.6 ± 2.3% at 25.0 mg/kg
(due to pyrithione’s affinity to metal the skin samples were ground in a stainless steel well, which is believed to be responsible for the low recoveries.)

Percutaneous absorption

Percutaneous absorption 1

Dose:

1 mg/kg

Parameter:

percentage

Absorption:

8 %

Remarks on result:

other: 48h

Percutaneous absorption 2

Dose:

25 mg/kg

Parameter:

percentage

Absorption:

2 %

Remarks on result:

other: 48h

Any other information on results incl. tables

	^14C-NaPT labelled compound
			% of dose
Compound applied			100
Compartments with compound detected			1 mg/kg		25 mg/kg
1.      Protective appliances			1.2±0.5		2.1±1.7
2.      Liquid used for washing the skin			32.7±4.8		13.8±0.7
3.      Skin (with substance not removable, e.g. skin wash, mineralized skin wash, dosed skin, mineralized tap strips)			9.3±3.5		78.1
4.      Blood	Whole blood	plasma	ND	ND	ND		ND
5.      Urine			4.8±0.9		1.4±0.2
6.      Faeces			0.8±0.1		0.2±0.1
7.      Removed organs specify organs give sum	Brain Kidneys Liver GI tract Spinal cord		0.00±0.00 0.02±0.01 0.31±013 0.54±0.31 <0.01±0.00		0.0±0.0 0.00±0.01 0.02±0.01 0.22±0.12 0.0±0.0
8.      Remaining carcass			0.8±0.2		0.2±0.1
9.      Cage rinsing			0.6±0.1		0.1±0.0
Sum of #4 – 9:   blood (WBld used), excreta, removed organs, remaining carcass (= absorption)			8.0		2.0
Sum of all detected labelled compound (#1 – 9) (=recovery)			68.3±7.8			77.6±2.3

Applicant's summary and conclusion

Conclusions:

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/kg and at 25 mg/kg the fraction absorbed decreased to 2%. Approximately 87% of the total radioactivity excreted in the 0-48 hr was in the urine. The fraction of the dose excreted in urine and feces decreased with increased dose. The concentration of 14C-NaPT equivalents in tissues typically was less than 0.05% of the dose with the exception of the liver at 1 mg/kg and intestines at the 1 and 25 mg/kg dose levels (which strongly suggests that14C-NaPT was ingested through preening). 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 Regulation EC 1907/2006.