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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, near guideline study, available as unpublished report, minor restrictions in design and/or reporting but otherwise adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
no
Remarks:
quality assurance audit of protocol and in-life monitoring took place, but the final report was not audited
Type of assay:
micronucleus assay

Test material

Constituent 1
Reference substance name:
light pyrolysis fuel oil
IUPAC Name:
light pyrolysis fuel oil
Constituent 2
Chemical structure
Reference substance name:
Gas oils (petroleum), steam-cracked
EC Number:
271-260-2
EC Name:
Gas oils (petroleum), steam-cracked
Cas Number:
68527-18-4
Molecular formula:
not applicable
IUPAC Name:
Gas oils (petroleum), steam-cracked
Details on test material:
- Name of test material (as cited in study report): light pyrolysis fuel oil
- Physical state: water white liquid
- Analytical purity: not reported
- Storage: at room temperature in amber glass

Test animals

Species:
mouse
Strain:
other: Crl:CD®-1 (ICR) BR Swiss
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, NY, USA
- Age at study initiation: 10-11 weeks
- Weight at study initiation: males 34-40 g, females 24-30 g
- Assigned to test groups randomly: yes (computer-assisted)
- Housing: individually in stainless steel cages
- Diet: Certified Rodent Chow #5002 (Ralston Purina Co., St Louis, MO, USA) ad libitum
- Water: filtered tap water ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: ~22±1°C (72±1°F)
- Humidity: 46±9 %
- Air changes: not reported
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: From: 3 April 1984 To: 16 May 1984

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
- Purity: 100%
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Prepared fresh daily. 2.5 g light pyrolysis fuel oil mixed with corn oil to 10 mL (for range-finding stage), 2.5 g light pyrolysis fuel oil mixed with corn oil to 50 mL for main micronucleus stage. Mixed by shaking.
Duration of treatment / exposure:
Range-finding: 2 consecutive days
Main test: 2 consecutive days (some animals at highest dose only 1 day)
Frequency of treatment:
once/day
Post exposure period:
50% of animals that received 2 doses killed on day 3 and 50% killed on day 4. Animals that received a single dose killed on days 2, 3 and 4. Positive controls killed on day 3.
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.25, 0.5, 1.0 g/kg
Basis:
nominal conc.
No. of animals per sex per dose:
10/sex for 0.25, 0.5 and 1.0 g/kg (2 doses) and negative controls; 4/sex positive controls; 15/sex for 1.0 g/kg (1 dose)
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Justification for choice of positive control(s): not reported
- Route of administration: intraperitoneal injection
- Doses / concentrations: 75 mg/kg

Examinations

Tissues and cell types examined:
bone marrow polychromatic erythrocytes
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: From results of range-finding stage, 80% of dose level which produced ≤50% mortality.

TREATMENT AND SAMPLING TIMES (in addition to information in specific fields): Negative control (corn oil) dosed at 20 mL/kg bw.

DETAILS OF SLIDE PREPARATION: Bone marrow smears stained with May-Grunwald and Giesma stains, examined at 400-1000 magnification.

METHOD OF ANALYSIS: 1000 PCEs and all mature erythrocytes were examined. The following were recorded: total PCEs, total normochromic erythrocytes (NORMs), PCEs with micronuclei, NORMs with micronuclei, group mean ratio of PCEs to NORMs.
Evaluation criteria:
Positive if statistically significant increase in micronucleated PCEs at any dose level with dose-response. Negative if neither previous criteria apply. Equivocal if only one criterion apply.
Statistics:
Treatment and group means compared using Student's t-test

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
all animals died in range-finding test at doses ≥2.5 g/kg, and 1 of 2 females died at 1.25 g/kg
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: 1.25, 2.5, 5.0 g/kg
- Clinical signs of toxicity in test animals: all died at ≥2.5 g/kg, 1 of 2 females died at 1.25 g/kg and surviving female lethargic. No effects on males at 1.25 g/kg.

RESULTS OF DEFINITIVE STUDY
- Mortality and clinical observations: 1 male died (1.0 g/kg x 2 doses), peri-anal soiling observed, no significant weight loss
- Induction of micronuclei (for Micronucleus assay): none
- Ratio of PCE/NCE (for Micronucleus assay): no significant change

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Light pyrolysis fuel oil was negative in the micronucleus test.
Executive summary:

Following oral dosing with Light Pyrolysis Fuel Oil (CAS 68527 -18 -4) at doses up to 1 mg/kg for 1-2 days mice did not show any significant change in micronucleus formation and there was no significant change in the ratio of polychromatic to normochromatic erythrocytes in bone marrow. Light pyrolysis fuel oil was negative in the micronucleus test.