Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
August 2003-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 data waiving:
other:

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
There was one deviation from the study protocol which was concerned with the relative humidity (section 6.2 husbandry). On some of the study days, the relative humidity was higher than 70%.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- 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% lead (II) oxide
- Impurities (identity and concentrations):
- Composition of test material, percentage of components: PbO: 99.8; metallic Pb: <0.01; Pb3O4: 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

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH
- Weight at study initiation: male 285-323 g; female: 187-218 g
- Housing:Before the animals arrived, the study room and cages were cleaned and disinfected. During the study, the room and cages were cleaned at regular intervals. The rats were hpoused individually in cages (Makrolon II).
- Diet (e.g. ad libitum): Teklad Global 18% Protein Rodent Diet (pelleted diet, batch no.204986) offered ad libitim.
- Water (e.g. ad libitum): Tap water as for human consumption was continuously available ad libitum via drinking bottles. Samples of drinking water are subjected to bacteriological tests, including the determination of chlorinated hydrocarbons, heavy metals and arsenic.
- Acclimation period: range finding: 15 days; main test: 21 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was adjusted to 22 +/-3
- Humidity (%): The relative humidity was kept between 38 and 78%. Maximum and minimum temperature and humidity were monitored daily.
- Air changes (per hr): Air was changed about 16 times per hour and filtered adequately.
- Photoperiod (hrs dark / hrs light): Artificial light was set to give a cycle of 12 hours light and 12 hours dark with light on at 7:00 AM.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: One day before each treatment, the fur was clipped from a dosal area of approx. 5X10 cm in each animal. The skin was subsequently examined for abrasions. Since the skin was healthy and intact, all animals were used for the test and coloured for individual identification.
- % coverage:
- Type of wrap if used: An occlusive dressing using a 4X5 cm patch (filter paper), Leukosilk and Elastoplast. To ensure good contact of the test article with the skin, a few drops of peanut oil were placed on the patch.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Patch Removal
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): The test article was used undiluted as supplied by the Sponsor
- Constant volume or concentration used: yes/no
- For solids, paste formed: No.


VEHICLE
- Amount(s) applied (volume or weight with unit): The solid test article was used undiluted as supplied by the Sponsor.
- Concentration (if solution):
- Lot/batch no. (if required): 210213
- Purity: 99.8% PbO
Duration of exposure:
The exposure period was 24 hours
Doses:
The rats were given a single dermal administration of the test artcle of 2000 mg/kg body weight.
No. of animals per sex per dose:
5 male and 5 female
Control animals:
not required
Details on study design:
In each animal a number of clinical-toxicological signs were evaluated according to a modified IRWIN Screening procedure (S. Irwin; Comprehensive Observational Assessment, Psychopharmacologia 134, 222-257, 1968) and observed findings were recorded. The animals were examined until 10min. p.a. and at the following post-treatment intervals: 1h, 2h, 6h, 24h and thereafter once daily up to day 14. Because of the occlusive dressing, the evaluation of some parameters were excluded until the 24-h observation time point. After patch removal, dermal irritation was evaluated once daily for14 days according to a scheme based on Draize. Body weights were recorded immediately before treatment and on days 7 and 14 p.a. (termination).

Results and discussion

Preliminary study:
The range finding test was conducted using 2 female animals which were treat
ed with the dose of 2000 mg.kg body weight. There were no deaths in the preliminary study.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No animal died during the course of the main test after the single dermal administration of 2000 mg/kg.
Clinical signs:
No abnormal clinical signs were observed. No skin irritation findings were seen.
Body weight:
After the first week, the body weight development was slightly influenced in most animals rather due to the administration procedure using the occlusive dressing than to the test article treatment. Decelerated weight gain was seen in one female animal (no. 10) as well as in one male animal (no.2) and slightly reduced body weight was seen in four female animals (no. 6 to 9). After two weeks, the weight gain was in the normal range known for wistar rats at this age.
Gross pathology:
Gross pathological examinations at day 14 p.a. (terminal necropsy) revealed no findings.
Other findings:
No specific findings.

Any other information on results incl. tables

On the basis of the results obtained after a single dermal administration of the test article "LITHARGE lead oxide" to Wistar rats, the LD50 values after 24 h and 14 days were as follows: Male and female > 2000 mg/kg

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information LD50 > 2000 mg/kg may be classified "non-toxic." Criteria used for interpretation of results: other: Draize
Conclusions:
No specific findings. On the basis of the results, obtained after a single dermal administration of the test article "LITHARGE lead oxide" to Wistar rats, the LD50 values after 24 h and 14 days were as follows: Male and Female > 2000 mg/kg. This value is higher than the limit specified as harmful by the EEC Directive 2001/59/EEC of 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1.I, p. 2233). When administered by the dermal route, the test article "Litharge lead oxide" may be classified as "non-toxic".
Executive summary:

The acute dermal toxicity of LITHARGE lead oxide was investigated in one group of rats comprising 5 males and 5 females. On the basis of the range finding test, the animals were given a single dermal administration of LITHARGE lead oxide at the dose of 2000 mg/kg. The skin was exposed to the test articles for 24 hours. Clinical observations were carried out at regular intervals during the 14 -day observation period. Signs of erythema and oedema were evaluated once daily for 14 days. Body weights were determoned immediately before treatment and on days 7 and 14 p.a. Gross pathological examinations were carried out at study termination on all animals. The following results were obtained:

- No animal died during the 14 -day observation period.

- No abnormal clinical signs were observed.

- No signs of or skin iiritation were observed.

- The body weight development was slightly influenced in most animals during the first week after treatment, possibly due to the administration procedure as such. At the end of the study, 14 days after treatment, the body weights were in the normal range

-Gross pathological examinations on day 14 p.a. did not reveal any findings in the rats.

Since no deaths were caused in Wistar rats after dermal treatment with the test article LITHARGE lead oxide of 2000mg/kg, the LD50 values after 24h and 14 days were as follows: Male and Female >2000 mg/kg

The above value is higher than the limit specified as harmful by the EEC Directive 2001/59/EEC of 6 August 2001 and the Gefahstoffverordnung (GedStoffV) of 15 November 1999 (BGB1.I, p. 2233). When administered by the dermal route, the test article LITHARGE lead oxide may therefore be classified as "non-toxic".

These results can be assigned to lead silicate since a read across based on a grouping of substances (Pb substances) is applied.