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Toxicological information

Basic toxicokinetics

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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:
other: 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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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

Test animals

Species:
rat
Strain:
other: F344/N Lovelace ITRI colony
Sex:
not specified
Details on test animals 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
Remarks:
Doses / Concentrations:
Day 1: 1 ppm, Day 2: 10 ppm, Day 3: 100 ppm, Day 4: 1000 ppm and Day 5: 5000 ppm
No. of animals per sex per dose:
2 rats per dose
Control animals:
not specified
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

Applicant's summary and conclusion

Conclusions:
Isobutane 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 absorption following inhalation exposure is reported by Dahl et al to be low (uptake 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.