Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles.
Justification for type of information:
See read-across justification provided in section 13.

Data source

Reference
Reference Type:
publication
Title:
Hydrocarbon nephropathy in male rats: identification of the nephrotoxic components of unleaded gasoline.
Author:
Halder CA, et al. (1985)
Year:
1985
Bibliographic source:
Toxicol. Ind. Health 1:67-87

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as detailed in publication
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: low viscosity liquid hydrocarbon

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Duration of treatment / exposure:
28 days
Frequency of treatment:
once daily, 5 days per week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
500 mg/kg/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
2000 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
10 rats/dose
Control animals:
yes

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Details on results:
CLINICAL SIGNS AND MORTALITY: There were no deaths. The dosages were well tolerated, with lethargy being the prominent clinical sign of toxicity.

BODY WEIGHT AND WEIGHT GAIN: The high dose group exhibited statistically significantly lower body weight gains than the saline control group.

GROSS PATHOLOGY: The most common pathologic findings were confined to the kidneys, stomachs, and, to a lesser degree, the livers. Stomach lesions appeared related to the irritant effect of the hydrocarbons on the stomach lining. Such lesions included erythema, erosion of the gastric mucosa, rasied discolored foci on the gastric epithelial lining and ulceration. The severity and incidence of these lesions were generally dose-related.

HISTOPATHOLOGY: NON-NEOPLASTIC: Renal: The test material induced a strong nephrotoxic response at both doses which was characterized by (a) hyaline droplet accumulation in the cytoplasm of epithelial lining cells of the proximal convoluted tubules, (b) degeneration or regeneration of the epithelial cells in the renal cortex, and (c) the development of granular proteinaceous casts in the lumina of tubules located between the inner and outer stripe of the medulla.

Effect levels

Dose descriptor:
LOEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Light hydrocarbon nephropathy mediated by alpha 2 microglobulin. Male rat specific effect, not relevant to human health

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The procedure was designed to investigate hydrocarbon nephropathy. Unleaded gasoline was used as a positive control.
Executive summary:

Four naphtha streams, among fifteen hydrocarbon compounds, were administered to two groups of male Fischer 344 rats by oral gavage at the dose levels of 500 mg/kg/day and 2000 mg/kg/day five days per week for four weeks. The procedure was designed to investigate hydrocarbon nephropathy. Animals in both groups experienced lethargy and significantly lower body weight gain was observed in the animals at the high-dose group. The only histopathological difference found was in the kidneys of all male rats. The kidney effects observed in male rats are indicative of alpha-2u-globulin nephropathy. These kidney effects are specific to male rats and are not considered to be of biological relevance to humans. Unleaded gasoline, the positive control, induced a strong nephrotoxic response.