Stoddard solvent

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Remarks:

Oral gavage application of different doses to rats 7 days/week, 28 days

Type of information:

other: published data

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

Oral gavage application of different doses to rats 7 days/week, 28 days; Determination of Body weights, clinical pathology and organ weights

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Kerosine (petroleum), hydrodesulfurized

EC Number:

265-184-9

EC Name:

Kerosine (petroleum), hydrodesulfurized

Cas Number:

64742-81-0

IUPAC Name:

Kerosine (petroleum), hydrodesulfurized

Specific details on test material used for the study:

Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%)

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Crj: CD (SD) rats
- Source: Charles River Breeding Laboratories (Portage, MI)
- Age at study initiation: 8 weeks
- Weight at study initiation (mean): males: 177-217 g; females: 134-149 g
- Housing: 5 per cage
- Diet ad libitum
- Water ad libitum
- Acclimation period: 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.3-25 (65-77 °F)
- Humidity (%): 35-60
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Groups of 5 rats of each sex were given doses of 0.14 (116 mg/kg), 0.42 (347 mg/kg), or 1.28 (1056 mg/kg) mL/kg of test substance in corn oil for 28 days. Animals were examined for clinical signs, mortality, body weight, food consumption, water consumption, and food conversion. After sacrifice clinical chemistry, hematology, clinical chemistry, urinalysis, organ weights, histopathology, and gross pathology were examined.

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days

Frequency of treatment:

Once per day,7 days/week, 28 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

116 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

347 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

1 056 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

Number of animals: 5 animals sex / dose group

Control animals:

yes

Details on study design:

- Post-exposure period: None; animals euthanized at end of 28-day treatment period

Positive control:

Sham-treated (corn oil) negative control.

Examinations

Observations and examinations performed and frequency:

Animals were examined for clinical signs, mortality, body weight, food consumption, water consumption, and food conversion.
After sacrifice clinical chemistry, hematology, clinical chemistry, urinalysis, organ weights, histopathology, and gross pathology were examined.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, all animals

HISTOPATHOLOGY: Yes, histopathological examination performed

Other examinations:

no data

Statistics:

According to Kaplan and Meier, method of Cox (1972) and Tarone's (1975) life table test

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, non-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:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, non-treatment-related

Neuropathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Other effects:

not examined

Details on results:

NOAEL = 1056 mg/kg
Hydrocarbons, C11-C14, n-alkanes, isoalkanes, cyclics, aromatics (2-25%) (CAS # 64742-81-0) using male and female Crj: CD (SD) rats. Groups of 5 rats of each sex were given doses of 0.14 (116 mg/kg), 0.42 (347 mg/kg), or 1.28 (1056 mg/kg) mL/kg of test substance in corn oil for 30 days. Animals were examined for clinical signs, mortality, body weight, food consumption, water consumption, and food conversion. After sacrifice clinical chemistry, hematology, clinical chemistry, urinalysis, organ weights, histopathology, and gross pathology were examined. There was no mortality during the experiment. Renal damage was observed in male rats at all dose levels. This type of renal pathology is specific to male rats due to an alpha2u-globulin-mediated process that is not relevant to humans. Female rats exhibited adaptive liver changes at the highest dosage and was not considered an adverse effect. The LOAEL for male rats was 0.14 ml/kg/day based on renal damage, which is not relevant to human health. The female NOAEL was 1.28 (1056 mg/kg) mL/kg.

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 056 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

Remarks on result:

other: based on renal damage

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Groups of 5 rats of each sex were given doses of 0.14 (116 mg/kg), 0.42 (347 mg/kg), or 1.28 (1056 mg/kg) mL/kg of test substance in corn oil for 28 days. Animals were examined for clinical signs, mortality, body weight, food consumption, water consumption, and food conversion. After sacrifice clinical chemistry, hematology, clinical chemistry, urinalysis, organ weights, histopathology, and gross pathology were examined. There was no mortality during the experiment. Renal damage was observed in male rats at all dose levels. This type of renal pathology is specific to male rats due to an alpha2u-globulin-mediated process that is not relevant to humans. Female rats exhibited adaptive liver changes at the highest dosage. There were no pathological findings of the liver and was therefore not considered an adverse effect. The LOAEL for male rats was 0.14 ml/kg/day based on renal damage, which is not relevant to human health. The female NOAEL was 1.28 (1056 mg/kg) mL/kg.

 

Applicant's summary and conclusion

Conclusions:

The LOAEL for male rats was 0.14 ml/kg/day based on renal damage, which is not relevant to human health. The female NOAEL was 1.28 (1056 mg/kg) mL/kg.
Based on based on renal damage at 1056 mg/kg bw the NOAEL was considered to be 1056 mg/kg bw/day

Executive summary:

Groups of 5 rats of each sex were given doses of 0.14 (116 mg/kg), 0.42 (347 mg/kg), or 1.28 (1056 mg/kg) mL/kg of test substance in corn oil for 28 days. Animals were examined for clinical signs, mortality, body weight, food consumption, water consumption, and food conversion. After sacrifice clinical chemistry, hematology, clinical chemistry, urinalysis, organ weights, histopathology, and gross pathology were examined. There was no mortality during the experiment. Renal damage was observed in male rats at all dose levels. This type of renal pathology is specific to male rats due to an alpha2u-globulin-mediated process that is not relevant to humans. Female rats exhibited adaptive liver changes at the highest dosage. There were no pathological findings of the liver and was therefore not considered an adverse effect. The LOAEL for male rats was 0.14 ml/kg/day based on renal damage, which is not relevant to human health. The female NOAEL was 1.28 (1056 mg/kg) mL/kg.