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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:
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 similar or equivalent to OECD TG 407 performed on an analogue substance.

Data source

Reference
Reference Type:
publication
Title:
Hydrocarbon nephropathy in male rats: identification of the nephrotoxic components of unleaded gasoline.
Author:
Halder CA, Holdsworth CE, Cockrell BY, Piccirillo VJ.
Year:
1985
Bibliographic source:
Toxicol. Ind. Health 1:67-87

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
Principles of method if other than guideline:
A series of gavage studies performed male F-344 rats using components of gasoline administered once daily, 5 days per wk for 4 wk (20 doses total).
GLP compliance:
not specified
Limit test:
yes

Test material

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:
Naphtha (petroleum), light catalytic cracked
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 for five 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 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:
no effects observed
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 (actual dose received)
Sex:
male
Basis for effect level:
body weight and weight gain
clinical signs
gross pathology
histopathology: non-neoplastic

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.