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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
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 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
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; Pb3O4:0.003; 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.

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: males:286-317 g: females: 192-199 g
- Housing: The rats were housed collectively at 3 animals per cage. Before animals arrived study room and cages were cleaned and disinfected. During study, room and cages were cleaned at regular intervals.
- Diet (e.g. ad libitum): Teklad Global 18% Rodent Diet offered ad libitum
- Water (e.g. ad libitum): Tap water as for human consumption was continuously available ad libitum via drinking water. Water subject to periodic bacteriological tests and to chemical analyses.
- Acclimation period: 23 days (females); 28 days (males)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 30-70
- Air changes (per hr): Air was changed about 16 times per hour and filtered adequately
- Photoperiod (hrs dark / hrs light): Artificia light was set to give a cyle of 12 hours light and 12 hours dark with light on at 7:00 AM.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% formulation of the test article
- Amount of vehicle (if gavage):10 ml/kg
- Justification for choice of vehicle:
- Lot/batch no. (if required): 072K0107 SIGMA
- Purity:


MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Initially the dose of 2000 mag/kg was administered to 3 male rats. Since no mortality was observed within a few days, the test article was administered subsequently to 3 male rats at the same dose of 2000 mg/kg.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females and 3 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The animals were examined 1 hr, 2 hr, 6 hr and 24 h after treatment and thereafter once daily up to day 14 of the study. Body weights were recorded immediately before treatment and days 7 and 14 p.a. (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy

Results and discussion

Preliminary study:
Initially, the dose of 2000 mg/kg was administered to 3 female rats. Since no mortality was observed within a few days, the test article was administered subsequently to 3 male rats at the same dose of 2000 mg/kg.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No male or female animal treated orally at the dose of 2000 mg/kg died prematurely
Clinical signs:
No clinical observations were observed in male and female animals during the 14-day observation period following the treatment at the dose of 2000 mg/kg.
Body weight:
There was no influence of the test article administered orally at the dose of 2000mg/kg on the body weight development in the male and female animals during the 14-day observation period.
Gross pathology:
Gross pathological examinations on day 14 p.a. (terminal necropsy) did not reveal test article-related findings.
Other findings:
spontaneous death n=0
killed in extremis n=0
terminal sacrifice 14 days p.appl. n=6

Animal no. Specific Findings
1-5 no specific findings
6 uterus: hydrometra

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: EU
Conclusions:
LD 50 >2000 mg/kg When administered by the oral route. The test article may therefore be classified as "non-toxic."
Executive summary:

The acute oral toxicity of LITHARGE lead oxide was investigated according to ATC method in one step using 3 male and 3 female rats. Three female animals were given a single oral administration of the test article Litharge lead oxide at a dose of 2000 mg/kg. Clinical observations were carried out at regular intervals during the 14-day observation period. Body weights were determined immediately before treatment and on 7 days and 14 p.a. Gross pathological examinations were carried out immediately at termination on all animals.

The following results were obtained:

-No animals died during the course of the 14-day observation period following the dose of 2000 mg/kg.

-No abnormal clinical signs were observed

-There was no influence of the treatment on the body weight development in all male and female animals during the 14-day observation period.

-Gross pathological examinations on day 14 p.a. did not reveal test article-related findings.

According to the EEC Directive 2001/59, 6 August 2001 and the Gefahrstoffverordnung (GefStoffV) of 15 November 1999 (BGB1. I, p.2233), the test article LITHARGE lead oxide can be classified as "non-toxic", since the oral LD50 value after 24 h and 14 days is expected to be higher than 2000 mg/kg in male and female Wistar rats.

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