Mixed LOF

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

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 413 TG under GLP conditions performed on an analogue substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

GLP compliance:

yes (incl. QA statement)

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:

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:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Scott Model 216 THA

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 hours per day five days per week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
7248 mg/m3
Basis:
analytical conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
12528 mg/m3
Basis:
analytical conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
21792 mg/m3
Basis:
analytical conc.

No. of animals per sex per dose:

20 males and 20 females per dose

Control animals:

yes, sham-exposed

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:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

CLINICAL SIGNS AND MORTALITY: High-dose males and females exhibited red material around the nose. Other clinical signs seen did not show any treatment-related trends. All animals survived to termination of the study.

BODY WEIGHT AND WEIGHT GAIN: Statistically significant decreases in mean body weights were noted in study weeks 2 through 13 for high-dose males and during weeks 4 and 5 for mid-dose males, when compared with control males. Group mean body weights were similar between control and treated females.

HAEMATOLOGY: There were no differences between exposed and control animals for any of the hematologic parameters which could be ascribed to the test material exposures.

CLINICAL CHEMISTRY: There were no differences between exposed and control animals for any of the biochemistry parameters which could be ascribed to the test material exposures.

URINALYSIS: There were a few statistically significant differences between exposed and control animals, but since all values were within the normal range, none of the differences were considered exposure related.

ORGAN WEIGHTS: At the terminal sacrifice, test article related organ weight changes were observed in the liver and kidney of male and female rats.

GROSS PATHOLOGY: No test article related macroscopic changes were observed in any of the male and female rats that were sacrificed after a 13 weeks exposure period.

HISTOPATHOLOGY: NON-NEOPLASTIC: There were test article related changes observed in the livers of male anf female rats and in the kidneys of male rats from the high-dose level.

HISTOPATHOLOGY: NEOPLASTIC: The liver change consisted of centrilobular hepatocellular hypertrophy involving scatted lobules. The liver cell enlargement was minimal. The incidence was slightly higher in male rats than in females (10/20 in males and 5/20 in females). The kidney changes in males consisted of: (a) granular casts within tubules located in the outer zone of the medulla, (b) tubular degeneration and regeneration, particularly in the proximal convoluted tubules, and (c) an increased incidence of chronic interstitial inflammatory recation. The severity of these changes varied from trace to mild and the distribution was multifocal. Most of the tubules that contained the granular casts appeared dilated with some degree of flattening and/or pressure necrosis of the lining epithelia. Degeneration of tubular epithelium was minimal, but regeneration was comparatively more prominent. Around some of these tubules there was infiltration with chronic inflammatory cells, primarily mononuclear cells. These changes occurred in other areas as well.

Effect levels

1

Dose descriptor:

NOAEC

Effect level:

ca. 21 792 mg/m³ air (analytical)

Sex:

female

Basis for effect level:

clinical signs

organ weights and organ / body weight ratios

2

Dose descriptor:

NOAEC

Effect level:

ca. 12 528 mg/m³ air (analytical)

Sex:

male

Basis for effect level:

body weight and weight gain

clinical signs

organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Exposure to light catalytically cracked naphtha (API 81-03) for 13 weeks produced mild but significant toxic responses in males, depressed body weights and typical hydrocarbon induced nephropathy. Female rats were essentially unaffected by the test material. Therefore, the male NOAEL was determined to be 12528 mg/m3 and the female NOAEL was concluded to be 21792 mg/m3.

Executive summary:

The purpose of this study was to evaluate the subchronic toxicity of light catalytically cracked naphtha when administered to Sprague-Dawley rats by whole body inhalation exposure for thirteen consecutive weeks at the analytical concentrations of 7248 mg/m3, 12528 mg/m3, and 21792 mg/m3. Very few responses were observed in male or females rats at the high-dose with the exception of red nasal discharge. Decreased body weight gain was observed in male rats of the mid- and high-dose groups. There were no exposure-related differences for either males or females in any of the hematologic, serum biochemical or urinalysis parameters evaluated. Exposure-related increases in the liver weights of male and female rats and the kidney weights of male rats were observed. Therefore, the male NOAEL was determined to be 12528 mg/m3 and the female NOAEL was concluded to be 21792 mg/m3.