Ethane

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Non GLP, non-guideline, animal experimental study. Minor restrictions in design and/or reporting but otherwise adequate for assessment.

Data source

Reference

Reference Type:

publication

Title:

Uptake of 19 hydrocarbon vapors inhaled by F344 rats

Author:

Dahl A, Damon E, Mauderly J, Rothenberg S, Seiler F and McClellan R

Year:

1988

Bibliographic source:

Fundam. Appl. Toxicol. 10, 262-269

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study to compare the rates of uptake of hydrocarbon vapours by rats.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Isobutane

EC Number:

200-857-2

EC Name:

Isobutane

Cas Number:

75-28-5

Molecular formula:

C4H10

IUPAC Name:

isobutane

Constituent 2

Reference substance name:

Butane

EC Number:

203-448-7

EC Name:

Butane

Cas Number:

106-97-8

Molecular formula:

C4H10

IUPAC Name:

butane

Test material form:

gas

Details on test material:

- Name of test material (as cited in study report): Isobutane and butane
- Other gases tested: Chemical classes included alkenes, alkynes, straight-chain and branched alkanes, alicyclics, and aromatics - specifically propene, 2-butyne, cis-2-butene, pentane, isopentane, neopentane, benzene, methylcyclopentane, hexane, isohexane, heptane, 2,3-dimethylpentane, octane, 2,3,4-trimethylpentane, 2,2,3,3,-tetramethylbutane, 1,2,4-trimethylbenzene, nonane
- Physical state: Gas
- Source: SGP-Ashland, South Plainfield, New Jersey, USA
- Analytical purity: 99.99%, both gases

Specific details on test material used for the study:

- Name of test material (as cited in study report): Isobutane and butane
- Other gases tested: Chemical classes included alkenes, alkynes, straight-chain and branched alkanes, alicyclics, and aromatics - specifically propene, 2-butyne, cis-2-butene, pentane, isopentane, neopentane, benzene, methylcyclopentane, hexane, isohexane, heptane, 2,3-dimethylpentane, octane, 2,3,4-trimethylpentane, 2,2,3,3,-tetramethylbutane, 1,2,4-trimethylbenzene, nonane
- Physical state: Gas
- Source: SGP-Ashland, South Plainfield, New Jersey, USA
- Analytical purity: 99.99%, both gases

Radiolabelling:

not specified

Test animals

Species:

rat

Strain:

other: F344/N Lovelace ITRI colony

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Lovelace ITRI colony
- Age at study initiation: 12-15 weeks
- Weight at study initiation: 264-339g
- Fasting period before study: Not stated
- Housing: Before exposure housed in polycarbonate cages (2 animals per cage) with hardchip bedding and filter caps.
- Diet: Lab Blox (Allied Mills, Chicago II, USA)ad libitum
- Water: ad libitum
- Acclimation period: Not stated

ENVIRONMENTAL CONDITIONS
- Temperature: 68-72°C
- Humidity: 20-50%
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: Not stated

Administration / exposure

Route of administration:

inhalation: gas

Vehicle:

other: air

Details on exposure:

TYPE OF INHALATION EXPOSURE: nose only

GENERATION OF TEST ATMOSPHERE / CHAMPER DESCRIPTION
- Exposure apparatus: Gas vapour was pumped at 400 mL/min from a Tellon supply bag through one sampling loop of a dual-column gas chromatograph, past the nose of a rat confined in a nose-only exposure tube, through the second sampling loop of the dual column gas chromatograph and, finally, into an exhaust bag.
- Method of holding animals in test chamber: confined in a nose-only exposure tube. The rat nose-only exposure tube was a modified plethysmograph and allowed for collection of respiration data during exposure.

Duration and frequency of treatment / exposure:

Exposure: 80 min for 5 consecutive days with daily escalation of vapour concentration

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1 ppm

Remarks:

Day 1

Doses / concentrations 2

Dose / conc.:

10 ppm

Remarks:

Day 2

Doses / concentrations 3

Dose / conc.:

100 ppm

Remarks:

Day 3

Doses / concentrations 4

Dose / conc.:

1 000 ppm

Remarks:

Day 4

Doses / concentrations 5

Dose / conc.:

5 000 ppm

Remarks:

Day 5

No. of animals per sex per dose / concentration:

2 rats per dose

Control animals:

not specified

Positive control reference chemical:

n/a

Details on study design:

The amount of hydrocarbon vapour absorbed was calculated from the output of the gas chromatograph and the flow rate past the rat's nose. Rat exposures were preceded by a 10-15 min pre-exposure equilibration/calibration period without a rat in the system.

Details on dosing and sampling:

Respiratory and gas chromatographic data were collected at 1-min intervals during the exposures which were typically 80 min in duration.
The analytical data were averaged over 10-min intervals between minutes 11 and 70 of each exposure, this smoothed the data and eliminated any erratic data recorded at the start of the exposures (caused by interruption of the air stream when the rat was introduced in the exposure tube into the apparatus after it had been equilibrated and calibrated). Minimal changes in the rate of uptake with time were recorded from the 11th through the 70th minutes of exposure, indicating that most of the tissue/blood/air equilibria were rapidly achieved.

Statistics:

No statistics done

Results and discussion

Preliminary studies:

No preliminary study done, other than exposing 2 naive rats to the highest vapour concentration to check for possible effects of high dose levels on uptake.

Main ADME results

Type:

absorption

Results:

Hydrocarbon vapours inhaled at 100ppm. Uptake of isobutane and butane was low (uptake 0.6-1.0 nmol/kg/min/ppm and 1.5-1.8 nmol/kg/min/ppm, respectively).

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Hydrocarbon vapours inhaled at 100ppm. Uptake of isobutane and butane was low (uptake 0.6-1.0 nmol/kg/min/ppm and 1.5-1.8 nmol/kg/min/ppm respectively).

Details on distribution in tissues:

Not measured

Details on excretion:

Not measured

Metabolite characterisation studies

Metabolites identified:

not measured

Details on metabolites:

n/a

Enzymatic activity

Enzymatic activity measured:

n/a

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

n/a

Any other information on results incl. tables

n/a

Applicant's summary and conclusion

Conclusions:

Isobutane and butane absorption following inhalation exposure is low.

Executive summary:

The comparative rates of uptake of 19 hydrocarbon vapours by rats were determined by a dual-column gas chromatograph method. Representative compounds from the chemical classes of alkenes, alkynes, straight-chain and branched alkanes, alicyclics, and aromatics were examined.

Isobutane and butane absorption following inhalation exposure is reported by Dahl et al. to be low (uptake of isobutane was 0.6 -1.0 nmol/kg/min/ppm, lower than butane at 1.5 -1.8 nmol/kg/min/ppm).

The authors propose that absorption rate increases with molecular weight, straight chain molecules will be more highly absorbed than branched isomers, and aromatic molecules will be more highly absorbed than paraffins. Thus isobutane and butane, which exist as a vapour at room temperature, is very poorly absorbed, and if absorbed, is normally rapidly exhaled.