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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:
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

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2000 mg/kg lead carbonate
Basis:
no data
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.