Dose-dependent uptake, distribution, and elimination of inhaled n-hexane in the Fischer-344 rat

Baker, Terrie S.; Rickert, Douglas E.

doi:10.1016/0041-008x(81)90364-1

Cited by 36 publications

(5 citation statements)

References 16 publications

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“…may indicate non-linear kinetics of n-nonane at these concentration levels. This observation is supported by results from Baker & Rickert (1981), indicating that the uptake and distribution of n-hexane is dose-dependent between 500 and 1000 p.p.rn. when inhaled for 6 hr, with a concentration of n-hexane in brain at 1000 p.p.m.…”

Section: Discussionsupporting

confidence: 67%

Inhalation Kinetics of C6 to C10 Aliphatic, Aromatic and Naphthenic Hydrocarbons in Rat after Repeated Exposures

Zahlsen

Eide

Nilsen

et al. 1992

Pharmacology & Toxicology

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The toxicokinetic properties of C6 to C10 n-alkanes, aromates and naphthenes have been investigated in rats during inhalation of 100 p.p.m. of the single hydrocarbons for 3 days, 12 hr/day. The concentration of hydrocarbon was measured by head space gas chromatography in blood, brain, liver, kidneys and perirenal fat at days 1, 2 and 3, immediately after termination of exposure and 12 hr after exposure on day 3. The main conclusions drawn from the study were: a) Aromatic hydrocarbons show high concentrations in blood and low concentrations in organs. b) Naphthenic hydrocarbons show low concentrations in blood and high concentrations in organs. c) n-Alkanes show very low concentrations in blood, relatively high concentrations in brain and a high potential for accumulation in fat with repeated exposures. d) Biological concentrations of hydrocarbons within one class increase in general with increasing molecular weight, though with specific exceptions. e) Accumulation is obviously influenced by differences in metabolism and enzyme induction potential. f) Lipid solubility is not the only parameter relevant for the evaluation of hydrocarbon accumulation.

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Section: Discussionsupporting

confidence: 67%

Inhalation Kinetics of C6 to C10 Aliphatic, Aromatic and Naphthenic Hydrocarbons in Rat after Repeated Exposures

Zahlsen

Eide

Nilsen

et al. 1992

Pharmacology & Toxicology

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“…Knowledge of the inhalation toxicokinetics of a substance is essential for understanding and extrapolating exposure dose-response relationships. There have been many papers on the inhalation toxicokinetics of n-hexane in humans and animals (Baker and Rickert, 1981;Bus et al, 1982;Fedtke and Bolt, 1987;Filser et al, 1987Filser et al, , 1996Hamelin et al, 2005;Perbellini et al, 1982;Wallace et al, 1997;Zahlsen et al, 1992). On the other hand, knowledge of the toxicokinetics for n-heptane (Filser et al, 1996;Zahlsen et al, 1992), n-nonane (Eide and Zahlsen, 1996;Zahlsen et al, 1990Zahlsen et al, , 1992, n-decane (Hissink et al, 2007;Perleberg et al, 2004;Wallace et al, 1997;Zahlsen et al, 1992), 2-methylpentane (Brugnone et al, 1979) and methylcyclopentane (Brugnone et al, 1979) is limited, and there has been no report on the toxicokinetics of 2,4-dimethylheptane.…”

Section: Introductionmentioning

confidence: 99%

Approach to estimation of absorption of aliphatic hydrocarbons diffusing from interior materials in an automobile cabin by inhalation toxicokinetic analysis in rats

Yoshida

2009

J of Applied Toxicology

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The interior air of an automobile cabin has been demonstrated in our previous studies to be contaminated by high concentrations of a large variety of aliphatic hydrocarbons diffusing from the interior materials. In the present study, the amounts of seven selected aliphatic hydrocarbons absorbed by the car driver were estimated by evaluating their inhalation toxicokinetics in rats. Measured amounts of the substances were injected into a closed chamber system in which a rat had been placed, and the concentration changes in the chamber were examined. The toxicokinetics of the substances were evaluated based on concentration-time courses using a nonlinear compartment model. Their absorption amounts in humans at the levels of actual concentrations in the cabins without ventilation were extrapolated from the results found with the rats. The absorption amounts estimated for a driver during a 2 h drive were as follows: 6 microg/60 kg of human body weight for methylcyclopentane (interior concentration 23 microg/m(3) as median value in previous study), 5 microg for 2-methylpentane (36 microg/m(3)), 13 microg for n-hexane (65 microg/m(3)), 51 microg for n-heptane (150 microg/m(3)), 26 microg for 2,4-dimethylheptane (97 microg/m(3)), 17 microg for n-nonane (25 microg/m(3)) and 49 microg for n-decane (68 microg/m(3)). An inverse relationship was found between the exposure and absorption among the substances (e.g. between n-decane and 2,4-dimethylheptane). These findings suggest that not only the exposure concentrations but also the absorption amounts should be taken into account to evaluate the health effects of exposure to low concentrations of volatile compounds as environmental contaminants.

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“…MnBK is further metabolized by c0-1 oxidation to 2,5-hexanedione, the neurotoxic metabolite, and by a-oxidation and decarboxylation to pentanoic acid. Following a 6-hr exposure of F-344 rats to 500, 1000, 3000, and 10,000 ppm of n-hexane, the blood concentrations of n-hexane and MnBK increased linearly with increasing exposure concentrations, but 2,5-hexanedione (HD) showed anamolous behavior (20). The concentration of HD at the end of hexane exposure increased substantially from 500 to 1000 ppm, then remained fairly constant between 1000 and 3000 ppm but was lower for the 10000 ppm n-hexane exposure than for the lower exposure levels.…”

Section: Physiologically Based Pharmacokinetic Modelingmentioning

confidence: 99%

Physiologically based pharmacokinetic analyses of simple mixtures.

Krishnan

Clewell

Andersen

1994

Environ Health Perspect

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Exposure to multiple chemicals may cause significant alterations of tissue dose of the toxic moiety of one or more of the individual chemicals. The change in target tissue dose of a chemical present in simple mixtures can be predicted when the determinants of disposition of each chemical, and the mechanism of toxicokinetic interaction between chemicals are understood at a quantitative level. Determinants of disposition include physiological (e.g., breathing rates, cardiac output, tissue volumes, blood flow rates), biochemical (e.g., kinetic constants for metabolism and protein binding), and physicochemical factors (e.g., blood:air and tissue:blood partition coefficients). Mechanisms of toxicokinetic interactions refer to the manner in which coexposure alters these determinants of disposition as compared to exposure to the individual chemicals. Interactions between chemicals can be described quantitatively with physiologically based pharmacokinetic (PBPK) models, which integrate these mechanistic determinants and permit prediction of alterations in tissue dose for various exposure situations by computer simulation. PBPK modeling studies of binary chemical interactions conducted so far indicate that inhibitory rather than potentiating metabolic interactions are more likely to be observed during multiple chemical exposures. As PBPK models of representative binary, tertiary and quaternary mixtures are developed, it will become increasingly possible to draw reliable conclusions about the risk associated with human exposure to chemical mixtures. -Environ Health Perspect 102(Suppl 9): 151-155 (1994)

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Dose-dependent uptake, distribution, and elimination of inhaled n-hexane in the Fischer-344 rat

Cited by 36 publications

References 16 publications

Inhalation Kinetics of C6 to C10 Aliphatic, Aromatic and Naphthenic Hydrocarbons in Rat after Repeated Exposures

Inhalation Kinetics of C6 to C10 Aliphatic, Aromatic and Naphthenic Hydrocarbons in Rat after Repeated Exposures

Approach to estimation of absorption of aliphatic hydrocarbons diffusing from interior materials in an automobile cabin by inhalation toxicokinetic analysis in rats

Physiologically based pharmacokinetic analyses of simple mixtures.

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