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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
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 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:
On some days of the study the relative humidity was higher than 70%.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): PEBETAL dibasic lead pthalate
- Molecular formula (if other than submission substance):
- 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, white powder
- Analytical purity: 74.15% Pb=97.6% Pebetal
- Impurities (identity and concentrations):
- Composition of test material, percentage of components: ash: 79.3; water:0.2
- Isomers composition:
- Purity test date:
- Lot/batch No.: D1/4296
- Expiration date of the lot/batch: July 31, 2004
- 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; shelf life: at least one year after dispatch
- Other:

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Harlan Winkelmann GmbH
- Age at study initiation:
- Weight at study initiation: male: 294-318 g; female: 186-211 g
- Fasting period before study:
- Housing: The rats were housed individually in cages
- Diet (e.g. ad libitum): Teklad Global 18% Protein rodent diet (pelleted diet, batch no.204986) offered ad libitum
- Water (e.g. ad libitum): Tap water as for human consumption was continuously available ad libitum via drinking bottles
- Acclimation period: 15 days (range finding); main test: 21 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- degrees centigrade
- Humidity (%): 38-78%
- Air changes (per hr): 16 times/hour and filtered adequately
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light with light on at 7:00 AM


IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day before treatment, the fur was clipped from a dorsal area of approximately 5 x 10 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.

The solid test article was used undiluted as supplied by the Sponsor. The animals were administered at the dose of 2000 mg/kg. The test article was held in contact with the skin by an occlusive dressing using a 4 x 5 cm patch (filter paper), Leukosilk and Elastoplast. To ensure good contact of the test article to the skin, a few drops of peanut oil were placed on the patch. The exposure period was 24 hours. All animals were weighed before dosingand the individual doses expressed as mg/kg were adjusted according to body weight.
Duration of exposure:
24 hours
Doses:
The rats were given a single dermal administration of the test article at a dose of 2000 mg/kg body weight.
No. of animals per sex per dose:
5 male and 5 female rats were each given a single administration of the test article at a dose of 2000 mg/kg body weight.
Control animals:
not required
Details on study design:
Since no test-article mortality occurred at the dose of 2000 mg/kg in the range of the finding test, a limit test was indicated employing one group of rats, comprising 5 male and 5 female animals. The rats were given a single dermal administration of the test article at a dose of 2000 mg/kg body weight. In each animal a number of clinical-toxicological signs were evaluated according to a modified IRWIN Screening procedure (S. Irwin; Comprehensive Observational Assessment. Psychopharmacologia 13, 222-257, 1968) and observed findings were recorded. The animals were examined until10 min. p.a. and at the following post-treatment intervals: 1 h, 2 h, 6 h, 24 h and thereafter once daily up to day 14. Because of the occlusive dressing, the evaluation of some parameters were excluded until the 24-hour observation time point. After patch removal, dermal irritation was evaluated once daily for 14 days according to a scheme based on Draize. Body weights were recorded immediately before treatment and on days 7 and 14 p.a. (termination). At the end of the observation period, the animals were sacrificed by CO2 asphyxiation and gross pathological examinations were performed subsequently.

Results and discussion

Preliminary study:
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 observation week, the body weight development was slightly influenced in some animals rather due to the administration procedure using the occlusive dressing than to the test article treatment. Slightly reduced body weight was seen in one male animal (no.5) as well as in three femaleanimals (no,6, 9 and 10). There was no weight gain in male animal no. 2. After two weeks, the weight gain was in the normal range as known for Wistarrats at this age.
Gross pathology:
Gross pathological examinations at day p.a. (terminal necropsy) revealed no findings.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information LD50 > 2000 mg/kg may be classified as "non-toxic" Criteria used for interpretation of results: other: DRAIZE
Conclusions:
On the basis of the results, obtained after a single dermal administration of the test article "Pebetal dibasic lead phthalate" to Wistar rats, the LD50 values after 24 hours and 14 days were as follows: Male and female >2000 mg/kg and can be classified as "non-toxic".














On the basis of the results, obtained after single dermal administration of the test article "PEBETAL dibasic lead phthalate" to Wistar rats, the LD50 values after 24 hours 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 thedermal route, the test article "Pebetal dibasic lead phthalate" may therefore be classified as "non-toxic."






































































































































































































LD50 values after 24 hours were >200 mg/kg. PEBETAL dibasic lead phthalate may therefore be classified as "non-toxic".






Executive summary:

The acute dermal toxicity of "PEBETAL dibasic lead phthalate" 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 "PEBETAL dibasic lead phthalate" at the dose of 2000 mg/kg. The skin was exposed to the test article for 24 hours. Clinical observations were carried out at regular intervals during the 14 -day observation period. Signs of erythma and oedema were evaluated once daily for 14 days. Body weights were determined 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 os skin irritation were observed.

-The body weight development was slightly influenced in some 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 the dermal treatment with the test article "PEBETAL dibasic lead phthlate"

of 2000 mg/kg, the LD50 values after 24hours 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 Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1.I, p.2233). When administered by the dermal route, the test article

"PEBETAL dibasic lead phthalate may therefore be classified as "non-toxic".

.