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Toxicological information

Eye irritation

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eye irritation, other
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 2002-December 2003
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-documented and corresponded to the requirements of the recommended Annex V Test Guidelines.
Justification for type of information:
No validated, guideline-conform experimental data on eye irritation are available for lead metal (powder), lead tetroxide, basic, tribasic and tetrabasic lead sulphate, neutral and dibasic lead stearate, dibasic lead sulphite, polybasic lead fumarate and basic lead carbonate. Instead of subjecting multiple sparingly soluble lead compounds to animal testing for eye irritation, only the following three lead compounds were selected for testing, based upon which extrapolation to the other not tested compounds could be justified: -lead oxide, since this is the compound to which workers will be most frequently exposed in the lead producing and processing industry, as well as in lead oxide and stabiliser manufacturing. -dibasic lead phosphite as an example of a lead compound with an inorganic anion, with a water solubility (12 mg/l) at the low end of the thirteen compounds tested, and because it represents a commercially relevant lead compound. -dibasic lead phthalate as an example of a lead compound with an organic anion, with a water solubility (580 mg/l) at the high end of the thirteen compounds tested. Given the unequivocally negative responses for the three selected lead compounds and the absence of eye irritating effects reported in the public domain, then by way of extrapolation it is considered reasonable that similar compounds not tested will also lack irritating properties for the eye. Therefore, it is proposed to waive further experimental testing for animal welfare reasons and the scientific observations made above.

Data source

Reference Type:
study report

Materials and methods

Test guideline
according to
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Details on test material:
Litharge-lead oxide
- Name of test material (as cited in study report): Litharge Lead oxide
- Molecular formula (if other than submission substance): PbO
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state: Fine yellow powder
- Analytical purity: 99.8%
- Impurities (identity and concentrations):
- Composition of test material, percentage of components: PbO:99.8; metallic Pb:<0.01; Pb304:0.003; Cu:<0.0001: Fe: 0.0008
- Isomers composition:
- Purity test date:
- Lot/batch No.: 210213
- Expiration date of the lot/batch: May 2005
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material: At room temperature
- Other:

Test animals / tissue source

New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: Harlan Winkelmann
- Age at study initiation:
- Weight at study initiation: 2.67, 3.00 and 3.84 kg
- Housing: Rabbits kept individually in a battery of cages with a cage size of 100 x 45 x 40 cm equipped with a paper disposal system.
- Diet (e.g. ad libitum): Teklad Global Rabbit Diet (pelleted diet) offerred ad libitum. Batches of diet are analysed periodically for a wide range of contaminants by Harlan Teklad
- Water (e.g. ad libitum): Tap water as for human consumption was continuously available ad libitum via drinking nipples. Samples of drinking water are subjected periodically to bacteriological tests and to chemical analyses, including the determination of chlorinated hydrocarbons, heavy metals, and arsenic.
- Acclimation period: animals have been housed at the testing facility for 27 days or several months

- Temperature (°C): 20 degrees C +/- 3
- Humidity (%): 30-70%
- Air changes (per hr): 16 times/hour
- Photoperiod (hrs dark / hrs light):12/12 with light on at 7:00 AM


Test system

unchanged (no vehicle)
other: The untreated left eye served as the control
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 0.1g
- Concentration (if solution):

- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
Three male rabbits used in the test were acclimatised to laboratory conditions for 27 days or several months. Twenty four hours before treatment, the eyes of all animals were examined for potential ocular lesions. Since the animals did not show ocular abnormalities, they were allocated to the test.The solid article was used as supplied by the Sponsor. One of the animals (rabbit no.1) was treated in advance in order to assess ocular reactions to the test article. The animal was treated with 0.1g of the solid test article, which was introduced into the conjunctival sac of the right eye after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about 1 second in order to limit loss of the test article. The untreated left eye served as the control. Since there was no remarkable response to the instillation of the test article within a few days, the further two animals were treated subsequently in the same manner.

Results and discussion

In vivo

Irritation parameter:
overall irritation score
animal #3
Time point:
24/48/72 h
ca. 0
fully reversible within: 24h
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Slight redness (grade 1) of the conjunctiva occurred in animal no.1 at 1 h after instillation and disappeared subsequently. No ocular findings were seen between 24 h after instillation and the end of observation 72 h after instillation. The mean grades of erythema at 24, 48 and 72 h after instillation were "0" in all animals.
Other effects:
No general toxic effects were observed.

Any other information on results incl. tables

Lead oxide is a non-irritant.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Migrated information Criteria used for interpretation of results: other: OECD 405
The test article was classified according to the EEC Directive 2001/59/EEC of 6 August 2001 and the Gefahrstoffverordnung (GEfStoffV) of 15 November 1999 (BGB1, p.2233). When administered to the eye, the test article is classified as "non-irritant."
Executive summary:

The purpose of this study was to assess irritant and/or corrosive effects of LITHARGE lead oxide on eyes and associated mucous membranes following ocular administration to rabbits. Information derived from this test serves to indicate the existence of possible hazards likely to arise from exposure of the eye to the test article.

The potential toxicity of LITHARGE lead oxide was assessed in an acute eye irritation/corrosion test on 3 albino rabbits. In each animal, 0.1g of the test article was introduced into the conjunctival sac of the right eye, the untreated left eye served as control. Both eyes were examined at 1, 24, 48 and 72 hours post applicationem. The following results were obtained:

Between 24 and 72 hours after instillation no ocular findings were seen. The only finding was slight redness of the conjunctivae in one animal 1 h after instillation.

No general toxic effects were observed.

The mean grades of ocular reactions 24, 48 and 72 hours after instillation were "0" in each animal.

The test article was classsified according to the EEC directive 2001/59/ECC of 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p. 2233). When administered to the eye, the test article LITHARGE lead oxide may therefore be classified as "non-irritant."