2,2,4-trimethylpentane

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions.

Data source

Reference

Reference Type:

publication

Title:

Assessment of unscheduled and replicative DNA synthesis in hepatocytes treated in vivo and in vitro with unleaded gasoline or 2,2,4 - trimethylpentane

Author:

Loury, D.J. et al.

Year:

1986

Bibliographic source:

Toxicology and Applied Pharmacology 85(1): 11-23

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)

Deviations:

yes

Remarks:

- limited documentation

GLP compliance:

not specified

Type of assay:

unscheduled DNA synthesis

Test material

Test material information

Constituent 1

Reference substance name:

2,2,4-trimethylpentane

EC Number:

208-759-1

EC Name:

2,2,4-trimethylpentane

Cas Number:

540-84-1

Molecular formula:

C8H18

IUPAC Name:

2,2,4-trimethylpentane

Details on test material:

- Name of test material (as cited in study report): 2,2,4-trimethylpentane
- Analytical purity: >99%

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories (Kingston, N.Y.)
- Weight at study initiation: 200-300 g
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

- Vehicle(s)/solvent(s) used: none

Duration of treatment / exposure:

one single dose

Frequency of treatment:

sinlge treatment

Post exposure period:

2, 12, 24 and 48 hours after dosing

Doses / concentrations

Remarks:

Doses / Concentrations:
500 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

3 males/ time period

Control animals:

yes

Positive control(s):

dimethylnitrosamine (DMN), dissolved in water
- Route of administration: orally
- Doses / concentrations: 10 mg/kg

Examinations

Tissues and cell types examined:

hepatocytes

Details of tissue and slide preparation:

see "any other information on materials and methods"

Statistics:

One-way analysis of variance was performed on UDS and S-phase data with multiple treatment groups. S-phase data were adjusted by square root transformation. Treatment means were compared to control means by Dunnett's multiple comparison test. Level of significance was <0.05.

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Remarks:

TMP did not induce unscheduled DNA synthesis in hepatocyte cultures from rats treated in vivo.

Toxicity:

no effects

Remarks:

Mean cell viabilities in preparations of hepatocytes were: 84 % at 2-12 hours after administration of 500 mg/kg TMP.

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

see "Remarks on results"

Any other information on results incl. tables

Mean cell viabilities in preparations of hepatocytes were: 85 % at 24 hours after administration of water (negative control) and 84 % at 2-12 hours after administration of 500 mg/kg TMP.

No increase in UDS expressed as increase in NG or number of cells in repair was observed in hepatocytes isolated from male rats at 2, 12, 24, or 48 hours post-dose. A strong response was elicited by the DMN positive control, as expected.

Autoradiographic preparations of hepatocytes isolated from rats 24 hr after treatment with TMP revealed a significant increase in the number of cells in S phase (2.1% vs 0.35% in controls); this value dropped back to 0.55% at 48 hours. TMP also significantly increased RDS in mice at 24 hours; no 48 hour values were presented. However low serum alanine transaminase activity were observed at 24 and 48 hours after a single treatment with 500 mg/kg TMP indicating that TMP induced little if any hepatocellular necrosis which could trigger regenerative cell proliferation.

Following 11 consecutive daily treatments with 100 mg/kg/day TMP, a significant increase (p<0.05) in rat hepatic concentration of DNA (mg/g liver) was seen but the total hepatic DNA content per rat was comparable to controls. Liver weight relative to body weight was also comparable to controls. The demonstrated increase in RDS suggests that TMP may stimulate additive rather than regenerative cell proliferation but not of sufficient magnitude to significantly increase the total DNA content of the liver.

TMP was administered at a single 500 mg/kg concentration to evaluate UDS and RDS in conjunction with a multidose study for unleaded gasoline. When RDS was observed, a liver DNA content determination was performed in rats with treatment over 11 days to determine the type of proliferative response.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: negative

Based on this study design 2, 2, 4- trimethylpentane does not induce unscheduled DNA synthesis in vivo by unchanged application via gavage.

Executive summary:

Based on this study design 2, 2, 4- trimethylpentane does not induce unscheduled DNA synthesis in vivo by unchanged application via gavage.