Pyrithione zinc

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex 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:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pyrithione zinc

EC Number:

236-671-3

EC Name:

Pyrithione zinc

Cas Number:

13463-41-7

Molecular formula:

C10H8N2O2S2Zn

IUPAC Name:

Bis [1-hydroxy-2(1H)-pyridinethionato-O,S](T-4)-zinc

Details on test material:

Batch Number: 3620165
Purity: 99.5%
Radiolabelling: 14C on the 2 and 6 position
Specific activity: 3.09 mCi/mmol (radiodiluted test substance = 0.4214 uCi/mg)

Radiolabelling:

yes

Test animals

Species:

human

Strain:

other: not applicable

Sex:

not specified

Details on test animals or test system and environmental conditions:

Human epidermal skin used

Administration / exposure

Type of coverage:

open

Vehicle:

water

Duration of exposure:

8 hours of exposure with 16 hours of post exposure monitoring

Doses:

Volume applied: 6.4 µL or 10 µL/cm2
Dose preparation:
The radiodiluted ZPT was formulated into the 48% aqueous dispersion to mimic the commercial product. Carboxymethyl cellulose and Darvan were blended with the radiodiluted ZPT (959.98 mg) with 1.00336 grams of water. The concentration of ZPT in the aqueous dispersion was 46.45% (w/w) (96.77% of the target concentration of 48% ZPT). The test preparation was verified for homogeneity with a coefficient of variation of 1.49%.

Details on study design:

Preparation of test site:
Four samples of full-thickness human (3 abdomen and 1 abdomen/breast) were obtained from patients aged 22 to 40 years old. All of the samples were obtained from NHS Lothian, St. John’s Hospital, Livingston, UK. On arrival at Charles River, these samples were cleaned of subcutaneous fat and connective tissue using a scalpel blade. The skin samples were washed in cold running water and dried using tissue paper. The skin samples were then cut into smaller pieces (where appropriate), wrapped in aluminium foil, put into self sealing plastic bags and stored at ca -20°C until they were used in the study or used immediately. The age and sex of the donor and site from which the skin was taken were recorded centrally and in the study records.
Test site size: 1.5 x 1.5 cm of the skin membrane was cut out and positioned onto the receptor chamber of the diffusion cell. Exposed surface area of the skin was 0.64 cm2. The receptor chamber volume was 0.25 ml.
Sampling schedule: Hourly fractions of receptor fluid from 0-8 hours post dose and then 2 hourly fractions from 8-24 hours.

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

[14C]-ZPT in an aqueous dispersion (46.45% measured ZPT a.i.) applied to human split-thickness skin I n vitro, showed that a majority of the applied dose (98.8%) was removed by washing at the 8 hour post application. At 24 hours post application, the total dislodgeable dose was 98.85% of the applied dose. The stratum corneum retained 0.46% of the applied dose; 0.30% was removed with the first 5 tape strips. The total unabsorbed dose was 99.31% of the applied dose. The absorbed dose, dermal delivery and potentially absorbable dose were <0.01% (0.16 µg equiv./cm2), 0.24% (14.43 µg equiv./cm2) and 0.41% (23.91 µg equiv./cm2) of the applied dose, respectively.

Total recovery:

Mass balance was determined to be 99.56% (SD = 1.30%) for labelled compound

Conversion factor human vs. animal skin:

Sample is human, no conversion required

Any other information on results incl. tables

Table A6_2-1.                 Table for Percutaneous Absorptionin vitroof ZPT Table 1                                      Distribution of Radioactivity (% Applied Dose) at 24 h Post Dose Following Topical Application of [^14C]‑Zinc Pyrithione in Aqueous DispersionTest Preparation (48%, w/w) to Human Split‑Thickness Skin
		Cell Number and Donor Number
		Cell 1	Cell 2	Cell 4	Cell 5	Cell 6	Cell 8	Cell 9	Cell 10	Cell 12		Cell 14
		0216	0216	0288	0288	0288	0294	0294	0294	0293		0293	Mean	SD
	Skin Wash	66.55	60.77	51.34	28.46	39.52	54.33	69.18	36.06	64.55		46.41	51.72	13.91
	Tissue Swab 8 h	32.03	36.83	49.90	70.33	59.72	44.99	28.57	59.29	35.49		53.30	47.05	13.78
	Pipette Tips	0.06	0.05	0.04	0.02	0.01	0.04	0.03	0.01	0.07		0.03	0.04	0.02
	Dislodegeable Dose 8 h	98.65	97.65	101.28	98.81	99.25	99.36	97.78	95.36	100.10		99.73	98.80	1.61
	Cell Wash	0.05	0.06	0.07	0.04	*0.03	0.10	0.08	*0.03	*0.03		0.04	°0.05	°0.02
	Tissue Swab 24 h	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00	0.01	*0.00	*0.00		0.00	°0.00	°0.00
	Total Dislodgeable Dose	98.70	97.71	101.35	98.85	99.28	99.46	97.87	95.39	100.13		99.78	98.85	1.62
	Stratum Corneum 1-5	0.42	0.16	0.05	0.16	0.12	0.33	0.50	0.46	0.14		0.68	0.30	0.21
	Stratum Corneum 6-10	0.06	0.05	0.01	0.02	0.03	0.22	0.13	0.17	0.03		0.08	0.08	0.07
	Stratum Corneum 11-15	0.05	0.05	*0.00	*0.01	*0.01	0.15	0.08	0.07	0.01		0.03	°0.05	°0.04
	Stratum Corneum 16-20	0.04	0.05	*0.01	*0.00	*0.00	0.08	0.06	0.04	0.02		0.04	°0.03	°0.02
	Stratum Corneum	0.56	0.31	0.07	0.20	0.17	0.78	0.77	0.73	0.20		0.83	0.46	0.30
	Unexposed Skin	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00		*0.00	°0.00	°0.00
	Total Unabsorbed	99.26	98.02	101.42	99.05	99.44	100.24	98.64	96.12	100.33		100.61	99.31	1.51
	Epidermis	0.16	0.28	0.01	0.02	*0.01	0.31	0.47	0.83	0.12		0.04	°0.23	°0.26
	Dermis	0.08	0.02	*0.00	0.00	0.00	0.01	0.02	0.02	0.00		0.01	°0.02	°0.02
	Receptor Fluid	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00		*0.00	°0.00	°0.00
	Receptor Rinse	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00	*0.00		*0.00	°0.00	°0.00
	Total Absorbed	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00		0.00	0.00	0.00
	Dermal Delivery	0.24	0.30	0.02	0.02	0.01	0.32	0.49	0.85	0.13		0.05	0.24	0.27
	Potentially Absorbable Dose	0.39	0.46	0.04	0.06	0.05	0.77	0.76	1.13	0.19		0.21	0.41	0.37
	Mass Balance	99.50	98.32	101.44	99.07	99.46	100.56	99.13	96.98	100.46		100.66	99.56	1.30

 

*=Results calculated from data less than 30 d.p.m. above background

°=Mean includes results calculated from data less than 30 d.p.m above background

Applicant's summary and conclusion

Conclusions:

In conclusion, topical application of 14C-ZPT in an aqueous dispersion applied to human skin in vitro resulted in the absorbed dose of 14C-ZPT being very low, <0.01% and when considering the labelled material in transit (tape strips 6-20) the resulting potential dermal absorption of ZPT following a typical 8 hour work shift would be 0.41%. The results obtained in this study indicate that the absorption of ZPT through human epidermis in vitro is extremely slow. 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.