Zinc oxide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Common breakdown product(s): This test was done on the hydrophobic coated zinc oxide nanoform which is assumed to be worst case. Zn2+ion determines the toxicity of ZnO and read across between various forms of ZnO (micro-scale, nano, coated or not) is fully supported. 

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical and target chemical are both nanoforms, with the same physical state (solid)
The source nanoform is Z-cote HP; Code: NM111; Surface coating: triethoxycaprylylsilane (2%); Substance type: Inorganic; Physical state: solid powder, nano-form
The target nanoform is Z-cote ®; Code: NM110; Surface coating: none; Substance type: Inorganic; Physical state: solid powder, nano-form

3. ANALOGUE APPROACH JUSTIFICATION
This test was done on the hydrophobic coated zinc oxide nanoform which is assumed to be worst case. Zn2+ion determines the toxicity of ZnO and read across between various forms of ZnO (micro-scale, nano, coated or not) is fully supported. 

4. DATA MATRIX
Source: Bellmann (2010), (KL1), acc. to OECD Guideline 402, rat LD50 > 2000 mg/kg bw
Target: uncoated ZnO nanoform NM110

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

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:

- Name of test material (as cited in study report): Z-COTE HP1
- Molecular weight (if other than submission substance): 81.38 g/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

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzefeld, Germany
- Age at study initiation: 10 - 11 weeks
- Weight at study initiation: males (mean): 308.92 g, females (mean): 193.28 g
- Housing: 2 rats of same sex per cage, wooden absorbing bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4 weeks

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

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: back

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000mg/kg bw
- Concentration (if solution): 0.5mg test item in 400µl corn oil
- Constant volume or concentration used: no
- For solids, paste formed: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex

Control animals:

other: untreated skin of same animal

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Twice a day, once on weekends
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, gross pathology

Statistics:

Means and standard deviation were calculated using standard statistical tests.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occured

Mortality:

Not observed

Clinical signs:

other: Slight signs of general discomfort as often seen in dermal toxicity studies, the general health status was good throughout the study

Body weight:

other body weight observations

Remarks:

Treatment related effects were not observed

Gross pathology:

No abnormalties detected

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the LD50 of nanoscaled ZnO is estimated to be > 2000mg/kg bw.

Executive summary:

The study was conducted to determine the acute dermal toxicity of nanoscaled ZnO according to the OECD Guideline 402 in compliance with GLP.

 

2000 mg/kg bw of the test substance were semiocclusively administered for 24 h as pasty formulation in corn oil to the shaved and defaffed back of 5 female and 5 male rats. After the end of the exposure period, the test substance paste was recovered as effectively as possible using water and the animals were observed for 14 d. During the present study no mortality occurred and there were no indications of systemic toxicity, no effects regarding the body weight and neither clinical signs nor pathological findings observed.

 

The LD50 of the test substance is therefore estimated to be > 2000 mg/kg bw.

 

This test was done on the hydrophobic coated zinc oxide nanoform which is assumed to be worst case. In conclusion  Zn²⁺ion determines the toxicity of ZnO and read across between various forms of ZnO (micro-scale, nano, coated or not) is fully supported.