Natural gas (petroleum), raw liq. mix

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 study report which meets basic scientific principles.

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

Guideline:

other: as detailed in publication

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Naphtha (petroleum), light catalytic cracked

EC Number:

265-056-2

EC Name:

Naphtha (petroleum), light catalytic cracked

Cas Number:

64741-55-5

IUPAC Name:

64741-55-5

Constituent 2

Reference substance name:

Light catalytic cracked naphtha

IUPAC Name:

Light catalytic cracked naphtha

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Duration of treatment / exposure:

4 weeks

Frequency of treatment:

once per day, 5 days per week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
500 mg/kg/day
Basis:
actual ingested

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2000 mg/kg/day
Basis:
actual ingested

No. of animals per sex per dose:

10 rats per dose

Control animals:

yes

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

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:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

no effects observed

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. Decreased body weight gain is consistent with alpha 2u-globulin-mediated nephropathy, an effect considered not relevant for human risk assessment.

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 weak-to-moderate nephrotoxic response 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. These effects are consistent with alpha 2u-globulin-mediated nephropathy, an effect considered not relevant for human risk assessment.

Effect levels

Dose descriptor:

NOEL

Effect level:

< 500 mg/kg bw/day (nominal)

Sex:

male

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The procedure was designed to investigate hydrocarbon nephropathy. The NOEL for light catalytic cracked naphtha was determined to be less than 500 mg/kg.

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. Light catalytic cracked naphtha induced a weak to moderate nephrotoxic response in a dose-dependent manner. The NOEL was determined to be less than 500 mg/kg.