Zinc oxide

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Zinc oxide

EC Number:

215-222-5

EC Name:

Zinc oxide

Cas Number:

1314-13-2

Molecular formula:

ZnO

IUPAC Name:

oxozinc

Test material form:

solid: nanoform

Details on test material:

NON-LABELLED TEST ITEM
- Name of test material (as cited in study report): Z-COTE HP1
- Molecular weight (if other than submission substance): 81.38g/mol
- Physical state: solid
- Composition of test material, percentage of components: Z-COTE HP1 (98%), coated with triethoxycaprylylsilane (CAS # 2943-75-1; 2%)
- Lot/batch No.: NPL Ref#: ZB250#65
- Expiration date of the lot/batch: June 2014
- Storage condition of test material: room temperature, dry, exclusion of light

RADIO-LABELLED TEST ITEM
- Name of test material (as cited in study report): [65Zn] Z-COTE HP1
- Composition of test material, percentage of components: Z-COTE HP1 (98%), coated with triethoxycaprylylsilane (CAS # 2943-75-1; 2%) radiolabelled by neutron activation of non-labelled test item (see obove)
- Specific activity (if radiolabelling): 0.882 MBq/mg (Nov 11, 2009), calculated specific activity on Feb 08, 2011 (dermal application): 0.240 MBq/mg

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation: 8 weeks
- Weight at study initiation: 260.6 g (mean)
- Housing: 2 rats per cage, absorbent softwooden bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 15%
- Air changes (per hr): fully airconditioned
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Administration / exposure

Type of coverage:

other: non-occlusive gauze with no contact to skin due to a spacer

Vehicle:

corn oil

Duration of exposure:

6 h

Doses:

20 mg Z-COTE HP1 per rat
1 MBq per rat

No. of animals per group:

5

Control animals:

yes

Remarks:

untreated skin of same animal was used as control

Details on study design:

DOSE PREPARATION
- Method for preparation of dose suspensions: The preparation of the suspensions was performed immediately before administration. 4.175 mg [65Zn] Z-COTE HP1 and 15.825 mg non-labelled Z-COTE HP1 were applied per rat in 80 mg corn oil. Resulting activity: 0.01 MBq / mg suspension
- Method of storage: freshly prepared

APPLICATION OF DOSE: with a spatula

VEHICLE: Corn oil
- Amount(s) applied (volume or weight with unit): 80 mg per rat
- Lot/batch no. (if required): MCBD4650

TEST SITE
- Preparation of test site: clipped, wiped with acetone
- Area of exposure: shoulder and back, 10cm2
- Type of cover / wrap if used: non-occlusive gauze cover using a spacer to avoid skin contact

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: non-occlusive gauze cover using a spacer to avoid skin contact

REMOVAL OF TEST SUBSTANCE
- Removal of protecting device: yes
- Washing procedures and type of cleansing agent: aqueous soap solution
- Time after start of exposure: 6 hours

SAMPLE COLLECTION
- Collection of blood: taken vom v. cava caudalis during necropsy
- Collection of urine and faeces: daily using metabolism cages
- Collection of expired air: not performed
- Terminal procedure: anesthesia with CO2, cutting of v. cava caudalis
- Analysis of organs: organ weights and radioactivity

SAMPLE PREPARATION
- Storage procedure: -20°C

ANALYSIS
- Method type(s) for identification: gamma counter Wallac Wizard 1470 from Perkin Elmer
- Liquid scintillation counting results (cpm) converted to dpm as follows: calibration curve
- Validation of analytical procedure: control sample of known radioactivity
- Limits of detection and quantification: 25.7 cpm

Results and discussion

Signs and symptoms of toxicity:

no effects

Dermal irritation:

no effects

Absorption in different matrices:

Means over all groups:
- Non-occlusive cover + enclosure rinse: 0.002 +/- 0.002 MBq (spacers), 0.007 +/- 0.003 MBq (O-rings), 0.003 +/- 0.012 MBq (gauze), 0.016 +/- 0.006 MBq (plasters),
- Skin test site: 0.143 +/- 0.057 MBq
- Skin wash/swabs: 0.667 +/- 0.101 MBq
- Blood: 0.0 MBq
- Organs: 0.0 MBq
- Urine: 0.0 MBq (group 1 and 2), 0.0000114 +/- 0.00001074 MBq (group 3)
- Cage wash + cage wipe: 0.0 MBq
- Faeces: 0.0 MBq (group 1 and 2), 0.000073 +/- 0.000133 MBq(group 3)

Total recovery:

- Total recovery: 94.79 +/- 8.34 %
- Recovery of applied dose acceptable: yes
- Limit of detection (LOD): 25.7 cpm
- Quantification of values below LOD or LOQ: no

Percutaneous absorption

Dose:

1 MBq or 20 mg Z-COTE HP1 /rat

Remarks on result:

other: 6 h

Remarks:

no absorption

Any other information on results incl. tables

With exception of trace amounts in some samples the radiolabelled test item was not excreted via urine or faeces, was not detected in blood, muscle, adipose tissue or other body compartments. In conclusion [65Zn] Z-COTE HP1 was not absorbed after dermal application in rats during the present study.

Applicant's summary and conclusion

Conclusions:

No systemic absorption, no penetration of Radiolabelled [65Zn] Z-COTE HP1 through the rat skin

Executive summary:

Radiolabelled [65Zn] Z-COTE HP1 was not absorbed after dermal application in rats during the present study.

A total of 15 male Wistar rats were treated topically with 2 mg/cm²[⁶⁵Zn] Z-COTE^®HP1 for6 hours. Necropsy was done for all animals immediately after the end of the exposure period (6h) and after 24, and 72 hours, respectively, to investigate dermal absorption of Z-COTE^®HP1. It was shown thatZ-COTE^®HP1 was not absorbed at all : in the group mean , 62 to 76% of the dose applied were recovered in the not absorbed fraction.The amount of radioactive Z-COTE^®HP1 in the stratum corneum, as determined from 10 adhesive tape strippings was found to be 14.9±5% of the applied dose after 6 hours (=immediately after the 6h exposure period) and 7.9±4 and 4.6± 3 % after 24 and 72 hours (= 18 or 66h after the 6h exposure period), respectively. The Z-COTE^®HP1 content in the remaining skin at the application site (viable skin + remaining stratum corneum) accounted for 10.2±6 % of the total dose after 6 hours and 16.3±5 and 16.4± 4% after 24 and 72 hours, respectively. No relevant radioactivity was found in faeces, urine, cage wash, organ or tissue samples. Recoveries of thetotal activity applied per rat ranged from 79 to 109 % (mean over all groups: 94%).