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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Toxicosis Associated with Dual Oral Exposure of Rats to Lead and Trichloroethylene
Author:
Jack Nunes, Marion Ehrich and John Robertson
Year:
2001
Bibliographic source:
Toxicol Pathol. 2001 Jul-Aug; 29(4):451-7

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Adult male rats were exposed orally to lead carbonate (2,000 mg/kg) for 9 days. Potential neurotoxicity was evaluated by using the Functional Observational Battery (FOB) recommended for neurotoxicity screening. Rats were sacrificed on day 16, and brain, testes, spleen, kidney/adrenals, heart, and liver weighed and observed for pathological changes.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Lead carbonate
EC Number:
209-943-4
EC Name:
Lead carbonate
Cas Number:
598-63-0
Molecular formula:
CH2O3.Pb
IUPAC Name:
λ²-lead(2+) carbonate
Details on test material:
- Name of test material (as cited in study report): lead carbonate
- Analytical purity: 100 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley, Indianapolis, Indiana
- Age at study initiation: 75 days old
- Weight at study initiation: 293 to 330 g
- Fasting period before study: 5 hr
- Housing: 2 per polycarbonate cage
- Diet: mouse/rat diet with 24 % protein, 4 % fat and 5 % crude fiber ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
lead carbonate: 16 days
trichloroethylene (TCE): 7 days (after 9 days of corn oil only)
lead carbonate + TCE: TCE for 7 days after lead carbonate for 16 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
2 mg/kg
Basis:
no data
No. of animals per sex per dose:
10 rats/group
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
BODY WEIGHT: Yes
- Time schedule for examinations: during the FOBs (Functional Observational Battery)

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at sacrifice
- How many animals: 5 randomly chosen rats/group

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: prior to the initial dosing, on day 9 prior to onset of TCE dosing, and during the dark cycle prior to sacrificing the animals 16 days into the study
- Dose groups that were examined: rats were randomized
- Battery of functions tested: according to the FOB (Functional Observational Battery): activity, autonomic nervous system function, excitability, convulsions, neuromuscular function and sensorimotor function
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
only with lead carbonate alone or +TCE
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
only with lead carbonate alone or +TCE
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
only with lead carbonate alone or +TCE
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
only with lead carbonate alone or +TCE
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
only with lead carbonate alone or +TCE
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
with lead carbonate alone or +TCE or with TCE
Histopathological findings: neoplastic:
not specified
Details on results:
BODY WEIGHT AND WEIGHT GAIN
Reduced body weight

HAEMATOLOGY
High blood lead levels

NEUROBEHAVIOUR
Decreases in grip strenght, foot splay, activity, alterations in ease of removing from the cage, piloerection, reaction to handling

ORGAN WEIGHTS
Reduced organ weights and significantly different organ-to-body weight ratios

GROSS PATHOLOGY
Marked decrease in testicular size, hemorhaging of the testicles, severely bloated stomachs, pale livers, absence of mesenteric fat

HISTOPATHOLOGY: NON-NEOPLASTIC
Increased incidence of chronic inflammation in the arterial wall of lungs, tubular cell inclusions, coagulated protein casts in tubular lumens, tubular dilation, vacuolization of periportal hepatocytes, increased incidence of single cell necrosis, gastritis, peritonitis

Effect levels

Dose descriptor:
NOAEL
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Organ weights; histopathology
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Lead toxicity was noted on many parameters when the FOB was used for examination of treated rats. Signicant decreases in body weight, rectal temperature, grip strength, foot splay, and activity were measured. Alterations in ease of removing from the cage, piloerection, and reaction to handling were noted as the FOB was done.

There were no differences between rats given lead only and rats given lead plus trichloroethylene (TCE). TCE had little effect on

most parameters measured during the FOB, although weight was somewhat reduced and foot splay was increased. Weight was reduced more in rats given the lead plus TCE combination or lead only when compared to rats given TCE only.

Applicant's summary and conclusion

Conclusions:
Lead carbonate toxicity appears to be the cause of the majority of the toxic consequences seen in this study.
Even with similar target organs, concurrent administration of lead carbonate plus TCE did not cause synergistic or even additive effects

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