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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 2003-December 2003
Reliability:
1 (reliable without restriction)

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 relaive humidity. 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:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
- Name of test material (as cited in study report): ALLSTAB LP 3139 dibasic lead phosphite
- Molecular formula (if other than submission substance): 2PbO x PbHPO3 x 0,5 H20
- Physical state: fine, white powder
- Analytical purity: 99.3%
- Composition of test material, percentage of components: Lead Content 82.7%; water 0,2%
- Lot/batch No.: 120510067
- Expiration date of the lot/batch: > 24 months after shipping
- Storage condition of test material: At room temperature

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: 292-334 g; female: 180-214 g
- Fasting period before study:
- Housing:The rats were housed individually in cages.
- Diet (e.g. ad libitum): Teklad Global 18% Protein Rodent Diet offered ad libitum
- Water (e.g. ad libitum): Tap water as for human consumption was continuously available ad libitum via drinking bottles.
- Acclimation period: range finding: 15 days; main test: 21 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- degrees centigrade
- Humidity (%): The relative humidity was kept between 38 and 78%.
- Air changes (per hr): 16 times per hour
- 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.


IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
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 test patch (filter paper), Leukosilk (Beiersdorf AG, Hamburg) and Elastoplast
(Beiersdorf AG, Hamburg). To ensure good contact of the test article with the skin, a few drops of peanut oil were placed on the patch. The exposure period was 24 hours.
Duration of exposure:
24 hours
Doses:
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:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were examined until 10 min. p.a. and at the following post-treatment intervals; 1 h, 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-hour
observation time point. Body weights were recorded immediately before treatment on days 7 and 14 p.a. (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Clinical Signs and Skin Reactions

Results and discussion

Preliminary study:
The range finding test was conducted using 2 female animals which were treated with the dose of 2000 mg/kg body weight. Since no test-article related mortality occurred at the dose of 2000 mg/kg in the range 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.
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 signs of skin irritation 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. The body weight was reduced in two male animals (no. 1 and 3) as well as in one female animal (no.8) and the weight gain was decelerated in two male animals (no. 2 and 4). After two weeks, the weight gain was in the normal range for most animals at this age, with the exception of females no. 9 and no. 10 which displayed a reduced body weight.
Gross pathology:
Gross pathological examinations at day 14 p.a. (terminal necropsy) revealed no test article-related findings.

Any other information on results incl. tables

 Body Weight (g)
 Animal No.  Sex  Day 0  Day 7 p.appl.  Day 14 p.appl.
 1  m  334  313  376
 2  m  292  299  308
 3  m  325  318  345
 4  m  306  308  326
 5  m  295  307  320
 6  f  188  201  210
 7  f  180  192  202
 8  f  214  196  219
 9  f  197  217  198
 10  f  198  215  203
         

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 "ALSTAB LP 3139 dibasic lead phosphite" to Wistar rats, the LD50 values after 24 hours 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 'ALLSTAB LP 3139 dibasic lead phosphite' may therefore be classified as "non-toxic".
Executive summary:

The acute dermal toxicity of "ALLSTAB LP 3139 dibasic lead phosphite" 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 "ALLSTAB LP 3139 dibasic lead phosphite" 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 erythema 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 animals died during the 14-day observation period

-No abnormal clinical signs were observed

-No signs of skin irritation were observed

-The body weight development was slightly influenced in some animals during the 2 week observation period, possibly due to the administration procedure using an occlusive dressing

-Gross pathological examinations on day 15 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 "ALLSTAB LP3139 dibasic lead phosphite" of 2000 mg/kg, the LD50 values after 24 hours 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 "ALLSTAB LP 3139 dibasic lead phosphite" may therefore be classified as "non-toxic".