Dialuminium zinc tetraoxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits

Author:

Gordon, T., et al.

Year:

1992

Bibliographic source:

Am Ind Hyg Assoc J 53(8): 503-509

Materials and methods

Principles of method if other than guideline:

Fischer 344 rats were exposed to the test material for 3 h. After 0, 4 or 24 h observation time animals were anesthetized and cellular/biochemical changes occurring in bronchoalveolar lavage fluid were examined.

GLP compliance:

not specified

Test type:

other: Pulmonary study

Limit test:

no

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:

OZn

IUPAC Name:

(oxido)zinc

Details on test material:

- Name of test material (as cited in study report): zinc oxide

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Weight at study initiation: 200-250 g
- Housing: hanging steel mesh cages
- Diet (e.g. ad libitum): standard laboratory animal chow (Purina Indianapolis Ind), ad libitum
- Water (e.g. ad libitum): sater, ad libitum

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Cannon 52 portchamber. LabProducts Inc., Maywood, NJ
- System of generating particulates/aerosols: Zinc granules were heated to approximately 550 °C in a crucible and the generated vapours were carried downstream by inert argon gas in the furnace to react with oxygen yielding zinc oxide vapours which was mixed with filtered air in a series of cooling/dilution heads before entering the exposure chamber.
- Method of particle size determination: Differential mobility analyzer (TSI Inc., St. Paul, Minn.)
- Temperature, humidity, pressure in air chamber: 25-30 °C and 30 %

TEST ATMOSPHERE
- Brief description of analytical method used: Monitored gravimetrically with teflon filters (Type FG 0.2 µm. Millipore, Bedford, Mass.) and Cahn balance (Model 21, Cahn InstrumentCerritos, Calif.) and filters were analyzed by atomic absorption spectroscopy periodically.

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 0.17 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

(Atomic absorption spectroscopy)

Duration of exposure:

3 h

Concentrations:

0, 2.5 and 5 mg/m³

No. of animals per sex per dose:

no data

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 0, 4 or 24 h
- Necropsy of survivors performed: Yes (animals were intraperitoneally anesthetized with Pentobarbital-390 mg/kg)
- Pulmonary lavage preparation: Tracheas were cannulated with sterile, blunt needles and lavaged twice with sterile, pyrogen-free, phosphate-buffered saline.
- Other examinations performed: Biochemical and cellular parameters like protein content, lactate dehydrogenase (LDH), β-glucuronidase level and cell counts were examined in bronchoalveolar lavage fluid.

Statistics:

Differences in lavage fluid parameters were analysed by one-way analysis of variance followed by a two-sided Dunnett's t-test.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

> 5 mg/m³ air

Exp. duration:

3 h

Effect levels 2

Sex:

male

Dose descriptor:

other: Increased level of total cell counts, protein content, LDH, and β-glucuronidase

Effect level:

2.5 mg/m³ air (nominal)

Exp. duration:

3 h

Mortality:

No mortality occured up to the end of the observation period.

Clinical signs:

other: Not applicable

Body weight:

Not applicable

Gross pathology:

Not applicable

Other findings:

- Other observations: Significant increases in protein content, lactate dehydrogenase (LDH), β-glucuronidase and cell counts were observed. The test material caused dose-dependent acute inflammation of lungs in rats under the conditions of this test.

Any other information on results incl. tables

LC50 values were not calculated within the publication. However, as no mortality was reported up to the end of the observation period, a LC50 > 5mg/m³ is considered.

Cellular and biochemical changes occurring in bronchoalveolar lavage fluid were examined. Significant increases in protein content, LDH, β-glucuronidase and cell counts were observed.

Table1: Retention of ultrafine test material particles

Exposure Conc.(mg/m^3)	Exposure duration (h)	Minute volume^A (L)	Total Zn Inhaled^B(µg)	Baseline Zn level^C, D(µg Zn/g tissue)	Zn Lung Burden^C(µg Zn/g tissue)	Total Zn Deposited^C, Eµg	Retention^C, F(%)
4.3	3	0.1	77	22.0 ± 0.8	34.0 ± 0.9	9.0 ± 0.8	11.5 ± 1.0

Where

^AMinute volume was calculated on the basis of the equation Y = aM^bwhere Y is minute volume; M is mass in kg; and a and b are the coefficient and exponent, respectively, derived by Stahl

^BTotal Zn inhaled = (exposure conc.) x (exposure duration) x (minute volume)

^CValues are mean ± SE

^DDerived from fumace gas-exposed animals.

^ETotal Zn deposited = {(Zn lung burden) - (baseline Zn level)} x (wet lung weight)

^F% retention = total Zn deposited / total Zn inhaled

Table 2: Exposure concentration

Target concentration	Actual concentration
2.5 mg/m^3	2.7 ± 0.1
5.0 mg/m^3	5.4±0.7

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008