[phthalato(2-)]dioxotrilead

Acute Toxicity: dermal

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

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. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[phthalato(2-)]dioxotrilead

EC Number:

273-688-5

EC Name:

[phthalato(2-)]dioxotrilead

Cas Number:

69011-06-9

Molecular formula:

C8H4O6Pb3

IUPAC Name:

[phthalato(2-)]dioxotrilead

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Name of test material (as cited in study report): PEBETAL dibasic lead pthalate
- 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
- Lot/batch No.: D1/4296
- Expiration date of the lot/batch: July 31, 2004
- Storage condition of test material: At room temperature; shelf life: at least one year after dispatch

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system 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:

other: LD50 > 2000 mg/kg may be classified as "non-toxic" under EU (CLP) criteria. However, a conclusion cannot be made on GHS criteria.

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".

.