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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Nov 1992-April 1993
Reliability:
2 (reliable with restrictions)
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:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: The experiments are being conducted in order to comply with Department of Transportation regulations on the transport of hazardous substances (49 CFR, section 173.132).
Deviations:
no
Principles of method if other than guideline:
All work was done in compliance with an approved, study-specific protocol.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dibasic lead Phthalate
- Molecular formula (if other than submission substance): Pb (CH6H4) (CO2)2.2PbO
- Molecular weight (if other than submission substance): 817.6
- 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: White powder, odorless
- Analytical purity: 100%
- Impurities (identity and concentrations):
- Composition of test material, percentage of components: 78.5% Lead oxide
- Isomers composition:
- Purity test date:
- Lot/batch No.: Lot no. 999; Sample No. 4255
- Expiration date of the lot/batch:
- 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: Stable, but avoid temperatures in excess of 400 degrees F.
- Storage condition of test material: To be stored at room temperature
- Other: High temperatures or fire may produce lead oxide fume, vapor or dust

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: At initiation of dosing 6-8 weeks old
- Weight at study initiation: 150-250 gm weight range
- Fasting period before study:
- Housing: The animals were housed individually in stainless steel suspension cages
- Diet (e.g. ad libitum): Agway Prolab 3000 ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Upon arrival at the laboratories the animals were housed separately from animals in the facility. The quarantine and laboratory acclimation period was one week in duration.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 69-74 degrees farenheit
- Humidity (%): 50-70%
- Air changes (per hr): Room air was filtered
- Photoperiod (hrs dark / hrs light): Lights were automatically cycled with 12 hours of light per day.


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: sodium carboxymethylcellulose (NaCMC)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 0.25%
- Justification for choice of vehicle:
- Lot/batch no. (if required):
- Purity:


MAXIMUM DOSE VOLUME APPLIED: 10ml/kg of body weight


DOSAGE PREPARATION (if unusual): Accurately weighed samples of dibasic lead phthalate were suspended in 0.25% sodium carboxymethylcellulose (Na CMC) solution at concentrations up to 200 mg/ml. The compound was added to one half the volume of Na CMC in a glass beaker and mixed with a glass rod to form a paste. The remaining Na CMC was added stirring and the resulting mixture was then sonicated for 5 minutes.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Range Finding Test- Animals (one male and one female) received oral doses of 250 mg/kg of dibasic lead phthalate. The animals were observed for 24 hours then a second pair of animals was dosed with 500 mg/kg. Animals were similarly observed for 24 hours prior to repeating the dosing/observation regimen with 1,000 mg/kg then 2,000 mg/kg. Individual body weights were recorded prior to the administration of the first dose then prior to the terminal sacrifice.
Doses:
2000 mg/kg of dibasic lead phthalate
No. of animals per sex per dose:
3 male and 3 female rats
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were recorded when the animals arrived in the laboratories, then daily for five consecutive days prior to the experiment and daily during the experiment. At the termination of the experiment the animals were sacrificed and subjected to gross necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Signs of chemically related toxicity, gastrointestinal examination

Results and discussion

Preliminary study:
Range Finding Test-The oral administration of doses of dibasic lead phthalate ranging from 250 to 2000 mg/kg to male and female rats produced neither lethality nor consistent grossly observable evidence of acute or delayed onset toxicity. The behaviors of dosed animals were indistinguishable from those of control animals. All animals receiving dibasic lead phthalate in the range finding test gained body weight during the observation period.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Since there were no signs of systemic or local toxicity associated with the 2000 mg/kg dose, it can be concluded that the "Lowest Observable Effect Level" (LOEL) is also greater than 2000 mg/kg.
Mortality:
All animals survived to the scheduled termination of the experiment.
Clinical signs:
There were no grossly observable signs of chemically related toxicity.
Body weight:
All animals gained weight during the experimental period and no treatment related trends were discernible.The mean body weights of dosed females were consistently greater than those of the control group, but this was a reflection of differences in beginning weights rather than the evidence of a treatment related effect. When dealing with relatively small groups of animals as in this study the randomization process frequently fails to produce equally weighted groups. However, since the rates of body weight gain in both the dosed and control groups were equivalent, the slight weight differences observed do not compromise the validity of the study.
Gross pathology:
The oral administration of 2000 mg/kg of dibasic lead phthalate to male and female rats produced no grossly observable evidence of toxicity. Gastric rugae were closely examined (in a blind fashion) during necropsy and there was no evidence of a treatment-related change. One male dosed with 2000 mg/kg exhibited the presence of a yellow fluid in the gastrointestinal tract.
Other findings:
- Organ weights:
- Histopathology:
- Potential target organs:
- Other observations: The behavior of dosed animals was indistinguishable from those of control animals.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information These results show that dibasic lead phthalate affords no acute toxicological hazard as defined by the Department of Transportation (Federal Register, 1990) and therefore requires no special consideration during transport. Criteria used for interpretation of results: other: US Department of Transportation (Federal Register, 1990)
Conclusions:
The results of this experiment lead to the conclusion that the acute LD50 value for dibasic lead phthalate in both male and female rats is greater than 2000 mg/kg. Further, since there were no signs of systemic or local toxicity associated with the 2000 mg/kg dose it can be concluded that the "Lowest Observable Effect Level" (LOEL) is also greater than 2000 mg/kg. These results show that dibasic lead phthalate affords no acute toxicological hazard as defined by the Department of Transportation (Federal Register, 1990) and therefore requires no special consideration during transport.
Executive summary:

This acute, oral toxicity study was conducted to assess the toxicological potential of dibasic lead phthalate in adult male and female rats in order to insure compliance with Department of Transportation regulations covering the transport of poisonous materials. The test material was suspended in 0.25% sodium carboxymethylcellulose and administered in volume doses of 1 ml/kg to young adult male and female Sprague Dawley derived rats. During the range finding test, groups of two males and two females received 250, 500, 1000, or 2000 mg/kg doses of dibasic lead phthalate. Animals were observed for signs of systemic toxicity and after 14 days they were subjected to complete gross necropsy which included visual examination of the mucosal surface of the gastrointestinal tracts. During the estimation of the acute oral LD50 value, groups of three male and three female rats received oral doses of 2000 mg/kg of dibasic lead phthalate. Animals were weighed and observed daily for 14 days then they were sacrificed and subjected to complete necropsy.

There was no evidence of either local or systemic toxicological consequences associated with the oral administration of dibasic lead phthalate. Body weight gains of dosed animals were similar to those of concurrent controls and there were no gross pathological findings that could be attributed to the administration of dibasic lead phthalate. Therefore, the acute oral LD50 value of dibasic lead phthalate in male and female rats is greater than 2000 mg/kg and the Lowest Observable Effect Level (LOEL) is also greater than 2000 mg/kg.

It is concluded that dibasic lead phthalate affords no acute toxicological hazard as defined by the Department of Transportation and requires no special consideration during transport.