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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is classified as reliable with restrictions because although the study did not follow an OECD guideline and it was not stated whether the study was GLP compliant, the study appears to be scientifically sound and there is an adequate level of detail.

Data source

Reference
Reference Type:
publication
Title:
Uptake of 19 hydrocarbon vapors inhaled by F344 rats
Author:
Dahl, A.R., Damon, E.G., Mauderly, J.L., Rothenberg, S.J., Seiler, F.A., McClellan
Year:
1988
Bibliographic source:
Fundamental and Applied Toxicology 10:262-269

Materials and methods

Objective of study:
absorption
Principles of method if other than guideline:
The study evaluates the uptake of select hydrocarbons by exposing rat via inhalation for 80 minutes for 5 consecutive days. Vapour uptake was calculated from gas chromatography data. Specifics on the study design and results are presented below.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Isopentane
- Substance type: C5 aliphatics
- Analytical purity: 99+%
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lovelace ITRI colony
- Age at study initiation: 12 to 15 weeks of age
- Weight at study initiation: 264 to 339 grams
- Housing: Prior to exposure, animals were housed 2 per cage in polycarbonate cages.
- Diet (e.g. ad libitum): Ad libitum; Lab Blox, Allied Mills, Chicago, IL
- Water (e.g. ad libitum): Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22.2°C
- Humidity (%): 20 to 50%
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Administration / exposure

Route of administration:
inhalation: vapour
Vehicle:
unchanged (no vehicle)
Details on exposure:
With regard to the exposure chamber, the vapour was pumped at 400 mL/minutes from a Teflon supply bag through one sampling loop of a dual -column gas chromatograph, past the nose, through the second sampling loop of the dual column gas chromatograph, and into an exhaust bag. Nose only exposures were conducted using a modified plethysmograph.
Duration and frequency of treatment / exposure:
80 minutes for 5 consecutive days (not counting weekend when no exposures were carried out)
Doses / concentrations
Remarks:
Doses / Concentrations:
1 ppm on day 1; 10 ppm on day 2; 100 ppm on day 3; 1000 on day 4; and 5000 ppm on day 5

The study only presents results for the 10 ppm dose group
No. of animals per sex per dose:
No data reported.
Control animals:
no
Positive control:
A positive control group was not used.
Details on study design:
- Dose selection rationale: No data reported.
- Rationale for animal assignment (if not random): No data reported.
Details on dosing and sampling:
The amount of hydrocarbon vapour absorbed was calculated from the out of gas chromatograph and the flow rate past the rat's nose. Vapour uptake was calculated from the following equation:

uptake (nmol/minute) = flow rate (litre/minute) x vapour concentration (nmol/litre) x ([PAinh(t)/PAinh(cal)] - [PAexh(t)/PAexh(cal)])
where flow rate is the flow rate past the rats' nose; vapour concentration is the supply vapour concentration; PAinh(t) is the chromatogram peak area of inhaled vapour at time t; PAinh(cal) is the chromatogram peak area of inhaled vapour from the pre-exposure calibration; PAexh(t) is the chromatogram peak area of exhaust vapour at time t; PAexh(cal) is the chromatogram peak area of exhaust vapour from the pre-exposure calibration.

Data were normalized twice: once for the mass of rats and to the concentration of inhaled vapour; the second to allow for direct comparison between uptakes rats obtained at different concentrations within the concentration range where little saturation effect was observed for many compounds. The following equation was used for normalization uptake:

Normalized uptake (nmol/min/kg/ppm) = uptake (nmol/minute)/(rat mass (kg) x vapour concentration (ppm))

The data were averaged over 10 minute intervals between 11 and 70 minutes of exposure. The report only discusses the interval from 60 to 70 minutes.
Statistics:
Probabilities were derived from the t test for comparison of the uptake rats of branched and straight-chain hydrocarbon vapours in rats.

Results and discussion

Preliminary studies:
A preliminary study was not conducted.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
When 2-methylbutane was inhaled at 10 ppm, the uptake ranges were 1.6±0.2 and 1.5±0.2 nmol/kg/min/ppm (the mean of two experiments).
Details on distribution in tissues:
No data reported.
Details on excretion:
No data reported.

Metabolite characterisation studies

Details on metabolites:
No data reported.

Any other information on results incl. tables

The number of animals used per compound per experiment is not reported. Abbreviated information on test methods and results was available because the study is a published article.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no data
The study authors concluded that (1) highly volatile hydrocarbons are less well-absorbed than less volatile hydrocarbons; (2) unsaturated compounds are better absorbed than saturated ones; and (3) branched hydrocarbons are less well-absorbed than unbranched ones.
Executive summary:

In a toxicokinetic study, F344 rats were exposed to a variety of hydrocarbon vapours, including 2 -methylbutane, via inhalation for 80 minutes for 5 consecutive days. Doses were as follows: 1 ppm on day 1; 10 ppm on day 2; 100 ppm on day 3; 1000 on day 4; and 5000 ppm on day 5. The study report only presents data for the 10 ppm dose.

When pentane was inhaled at 10 ppm, the uptake ranges were 1.6±0.2 and 1.5±0.2 nmol/kg/min/ppm (the mean of two experiments). Additionally, the uptake rate of pentane was greater than that of 2 methylbutane. The study authors concluded that (1) highly volatile hydrocarbons are less well-absorbed than less volatile hydrocarbons; (2) unsaturated compounds are better absorbed than saturated ones; and (3) branched hydrocarbons are less well-absorbed than unbranched ones.

This study received a Klimisch score of 2 and is classified as reliable with restrictions because although the study did not follow an OECD guideline and it was not stated whether the study was GLP compliant, the study appears to be scientifically sound and there is an adequate level of detail.