Trilead bis(carbonate) dihydroxide

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting 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. [Toxicologic pathology]

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

To determine if additive or synergistic toxic effects would occur, adult male rats were exposed orally to lead carbonate for 9 days
before trichloroethylene (TCE), was given concurrently for an additional 7 days

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Lead carbonate

EC Number:

209-943-4

EC Name:

Lead carbonate

Cas Number:

598-63-0

Molecular formula:

CH2O3.Pb

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-day old
- Weight at study initiation: 293-330 g
- Fasting period before study: 5-hour
- Housing: 2 per polycarbonate cage
- Diet (e.g. ad libitum): 24% protein, 4% fat and 5% crude fiber (Tekland 7001)
- 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:

9 to 16 days

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
2000 mg/kg lead carbonate
Basis:
no data

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2000 mg/kg TCE
Basis:
no data

No. of animals per sex per dose:

10 animals/group

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT: Yes
- Time schedule for examinations: when the FOBs were done

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: prior to the initiation, on day 9 prior to onset of TCE dosing, and during the dark cycle
- Dose groups that were examined: randomized
- Battery of functions tested: activity, autonomic nervous system function, excitability, convulsions, neuromuscular function, sensorimotor function

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

not examined

Mortality:

not examined

Body weight and weight changes:

effects observed, treatment-related

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:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

effects observed, treatment-related

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

BODY WEIGHT AND WEIGHT GAIN
Significant decrease in body weight for treated rats

NEUROBEHAVIOUR
Significant decrease in grip strenght, foot splay and activity
Alterations in ease of removing from the cage, piloerection and reaction to handling

ORGAN WEIGHTS
Weights of the testes, spleen, heart, and liver reduced in rats given lead or lead + TCE

GROSS PATHOLOGY
All animals dosed with lead: marked decrease in testicular size, hemorrhaging of the testicles, severely bloated stomachs, pale livers, and a nearly complete absence of mesenteric fat

HISTOPATHOLOGY: NON-NEOPLASTIC
TCE: increased incidence of chronic in ammation in the arterial wall of lungs
lead and lead+TCE: included tubular cell inclusions, coagulated protein casts in tubular lumens and tubular dilation (kidney), vacuolization of periportal hepatocytes, increased incidence of single cell necrosis (liver), severe ulceration and necrosis of the gastric glandular, gastritis, hyperplasia and peritoniti, degeneration and necrosis of seminiferous epithelium mucosa

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The present study indicated that even with similar target organs, concurrent administration of lead plus TCE did not cause synergistic or even additive effects.
Lead toxicity appears to be the cause of the majority of the toxic consequences seen in this study, overshadowing any effects of concurrent addition of TCE.