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Description of key information

Reliable animal data were found indicating that lead oxide (and lead phosphite and dibasic lead phthalate) lack irritating properties for the skin or the eyes.

Sparingly soluble lead compounds do not exhibit irritant or corrosive properties in acute inhalation studies. There are no reports of respiratory irritation in occupationally exposed workers.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August-December 2003
Reliability:
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:
Appropriate in vivo study was already available. No need to perform in vitro study.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
There was one deviation from the study protocol which was concerned with the relative humidity (section 6.2 Husbandry). At some days of the study the relative humidity was higher than 70%.
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
- Name of test material (as cited in study report): LITHARGE lead oxide
- Physical state: fine, yellow powder
- Analytical purity: 99.8% lead (II) oxide
- Composition of test material, percentage of components: PbO: 99.8; metallic Pb: 0.01; Pb3O4:0.003; Cu: 0.001: Fe: 0.0008
- Lot/batch No.: 210213
- Expiration date of the lot/batch: May 2005
- Storage condition of test material: At room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann
- Age at study initiation:
- Weight at study initiation: 2.67, 2.84 and 3.86 kg
- Housing: The rabbits were housed individually in a battery of cages with a cage size of 100 x 45 x 40 cm (L x B x H), equipped with a paper disposal system.
- Diet (e.g. ad libitum): Teklad Global Rabbit Diet (pelleted diet, batch no. K088) offered ad libitum.
- Water (e.g. ad libitum): Tap water as for human consumptiion was continuously available ad libitum via drinking nipples.
- Acclimation period: The animals were acclimatised to laboratory conditions for more than 5 days. Animals were housed at the testing facility for 20 days or several months


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 degrees centigrade
- Humidity (%): The relative humidity was kept between 44 and 72%.
- Air changes (per hr): Air was changed 16 times per hour and filtered adequately.
- Photoperiod (hrs dark / hrs light):12 hours dark/12 hours light with light on at 7:00 AM


IN-LIFE DATES: From: To:
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Remarks:
The skin of the back of all animals was clipped 24 hours before treatment and examined for potential lesions. Only healthy animals showing no evidence of abnormalities were allocated to the test. The untreated left side of the back served as control.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, and 72 hours after exposure
Number of animals:
three albino rabbits
Details on study design:
TEST SITE
- Area of exposure: Clipped skin on the right side of the back of rabbit
- % coverage:
- Type of wrap if used: Gauze patch


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


SCORING SYSTEM:
Irritation parameter:
other: Grading of skin as stipulated by OECD 404
Basis:
mean
Time point:
other: 24, 48, and 72 hours after the end of the 4 hour exposure
Score:
0
Max. score:
0
Irritant / corrosive response data:
There were no skin irritating findings with the exception of very slight signs of erythema observed 1 hour after patch removal in all three animals.
The mean grades at 24, 48, and 72 hours after the end of exposure were "0" in each animal.
Other effects:
No general toxic effects were seen
Interpretation of results:
other: Not classified under EU (CLP) criteria. However, a conclusion cannot be made on GHS criteria.
Conclusions:
The test substance was classsified on the basis of the mean values of skin reactions 24, 48 and 72 hours after the end of the 4-hour exposure accordingto the EEC Directive 2001/59/EEC of 6 August 2001 and Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p. 2233). When applied to the skin, the test substance "LITHARGE lead oxide" is classified as "non-irritant."
Executive summary:

The potential toxicity of "LITHARGE lead oxide" was assessed in an acute dermal irritation/corrosion test on three albino rabbits. In each animal, 0.5 g of the solid test substance was applied on the right side of the dorsal clipped region, the untreated left side served as control. Exposure duration was 4 hours. Both sides were examined at 1, 24, 48, and 72 hours after the end of exposure. The following results were obtained:

-No signs of erythema and oedema were observed

-No general toxic effects were seen

-The mean grades at 24, 48, and 72 hours after the end of exposure were "0" in each animal.

The test article was classsified on the basis of the mean values of skin reactions 24, 48 and 72 hours after the end of the 4-hour exposure according to the EEC Directive 2001/59/EEC of 6 August 2001 and Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p. 2233). When applied to the skin, the test substance "LITHARGE lead oxide" is classified as "non-irritant."

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 2002-December 2003
Reliability:
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:
Appropriate in vivo study was already available. No need to perform in vitro study.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
Litharge-lead oxide
- Name of test material (as cited in study report): Litharge Lead oxide
- Molecular formula (if other than submission substance): PbO
- Physical state: Fine yellow powder
- Analytical purity: 99.8%
- Composition of test material, percentage of components: PbO:99.8; metallic Pb:<0.01; Pb304:0.003; Cu:<0.0001: Fe: 0.0008
- Lot/batch No.: 210213
- Expiration date of the lot/batch: May 2005
- Storage condition of test material: At room temperature
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- 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


ENVIRONMENTAL CONDITIONS
- 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


IN-LIFE DATES: From: To:
Vehicle:
unchanged (no vehicle)
Remarks:
The untreated left eye served as the control
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1g
- Concentration (if solution):


VEHICLE
- 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.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
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.

Lead oxide is a non-irritant.

Interpretation of results:
other: Not classified under EU (CLP) criteria. However, a conclusion cannot be made on GHS criteria.
Conclusions:
The test substance 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 substance 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 substance.

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 substance 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 substance LITHARGE lead oxide may therefore be classified as "non-irritant."

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Reliable animal data were found indicating that lead oxide, lead phosphite and dibasic lead phthalate lack irritating properties for the skin or the eyes. The experimental data are reinforced by a lack of reports of skin or eye irritation in the many occupational exposure environments which provide opportunities for exposure of lead and sparingly soluble lead compounds to the skin and eyes. Classification for these endpoints is clearly not needed. Specific studies of lung irritation were not found, but the lack of inhalation toxicity from lead oxide in both acute toxicity testing and inhalation cancer bioassays combine with an absence of reports of lung irritation in occupational settings to suggest classification is not needed.

The substances for which data are available should permit data waiving for a number of other substances. The three tested compounds are all sparingly soluble (and thus unlikely to undergo significant dissolution when applied to the skin, eyes or inhaled. The tested compounds further include one compound with an organic anion and one with an inorganic anion. Literature searches have failed to identify anions in other sparingly soluble substances that would alter the irritant properties of other sparingly soluble lead salts. Finally, dermal, oral and inhalation toxicity studies for lead compounds are uniformly negative and further support a finding of no irritant properties. Data waiving for all irritant classification endpoints should thus be possible for metallic lead and other sparingly soluble lead salts (unless anions are present that literature searches suggest might impart irritating properties.

No studies were found documenting corrosive properties of lead and sparingly soluble lead compounds in either experimental animals or humans. Given the negative findings of acute toxicity and irritation studies and the absence of reports from occupationally exposed workers, corrosive properties are not to be expected of lead or its sparingly soluble compounds.


Justification for selection of skin irritation / corrosion endpoint:
Well-documented and corresponded to the requirements of the recommended Annex V test guidelines

Justification for selection of eye irritation endpoint:
Well-documented and corresponded to the requirements of the recommended Annex V test guidelines

Justification for classification or non-classification

No skin or eye irritation observed in experimental studies conducted according to Annex V test guidelines.

No evidence of respiratory irritation in rat acute toxicity studies up to 5mg/L and no reports of respiratory irritaion following extensive use of this substance in the workplace.