Biomedical subjects

O G Nilsen

Publications and source records attributed to O G Nilsen.

At least 19 recordsLinked to original sources

PubMed2001

Single- and multiple-dose pharmacokinetics, kidney tolerability and plasma protein binding of tenoxicam in renally impaired patients and healthy volunteers.

The 20 mg single-dose and 12 days repeated-dose pharmacokinetics of tenoxicam and the 5-OH-tenoxicam metabolite have been evaluated in healthy volunteers and two groups of patients with different degree of renal impairment, in total 20 persons. Concomitantly, the plasma protein binding of tenoxicam and the effects of treatment on renal function were evaluated. No differences were found between the investigated groups in the pharmacokinetics of total tenoxicam and the 5-OH metabolite did not interfere either with the pharmacokinetics or with the plasma protein binding of tenoxicam. A positive correlation was found between an increase in the free fraction (% F) of tenoxicam in plasma and a decrease in the plasma elimination half-life in the low creatinine clearance group (40-20 ml/min.) both after the single-dose and at steady-state. At steady-state, a non-linear correlation was demonstrated between a decrease in the urinary excretion of the 5-OH metabolite and a decrease in creatinine clearance from 130 to 20 ml/min. An increase in the plasma level of the 5-OH metabolite by three times was found in the low creatinine clearance group as compared to healthy subjects. 14C-Impurities of tenoxicam, as low as 1.2%, were shown to greatly influence the determination of the plasma protein binding (equilibrium dialysis) of the highly protein-bound tenoxicam due to a non-binding ability of the impurities to plasma proteins. No significant changes in renal parameters were found during the study. It can be concluded that the pharmacokinetics and plasma protein binding of tenoxicam and the pharmacokinetics of the 5-OH-tenoxicam metabolite are increasingly changed in subjects with a creatinine clearance below 40 ml/min. A decreased binding of tenoxicam to plasma proteins in low clearance patients is probably the reason for a faster elimination of tenoxicam in this group rather than a higher intrinsic hepatic metabolic activity. This study conducted in a low number of patients did not bring forward any new data indicating any adverse effects of tenoxicam on renal function.

Adult↗

PubMed2000

Prediction of in vivo metabolic clearance of 25 different petroleum hydrocarbons by a rat liver head-space technique.

In vitro rates of metabolism and Michaelis-Menten constants were determined for 25 different C6 to C10 hydrocarbons using rat liver slices in a vial head-space equilibration system. The rates of metabolism were compared with steady-state levels obtained in vivo in the same strains of rats after inhalation. Aromates were metabolized at a higher rate than naphthenes n-alkanes, isoalkanes and 1-alkenes. The aromates showed, in contrast to the other hydrocarbons investigated, increased metabolism with increasing number of carbon atoms up to C8 (o-xylene, the most extensively metabolized compound). The in vivo steady-state concentrations of the aromates in blood were inversely related to the in vitro efficiency of their metabolism. This explains the pattern of blood levels observed for the C6 to C10 aromates in the rat after inhalation, with o-xylene demonstrating the lowest concentration. In general, the extent of tissue metabolism of the investigated hydrocarbons might be of greater importance for their body distribution than their lipophilicity, especially for the highly metabolized compounds. The high in vitro intrinsic liver clearances found for the aromates indicate a flow-dependent metabolism of these hydrocarbons in vivo. The head-space liver slice equilibration system seems to work adequately for metabolic studies of hydrocarbons with different volatility and water solubility.

Animals↗

PubMed1999

Measurement of HPRT mutations in splenic lymphocytes and haemoglobin adducts in erythrocytes of Lewis rats exposed to ethylene oxide.

Young adult male Lewis rats were exposed to ethylene oxide (EO) via single intraperitoneal (i.p.) injections (10-80 mg kg-1) or drinking water (4 weeks at concentrations of 2, 5, and 10 mM) or inhalation (50, 100 or 200 ppm for 4 weeks, 5 days week-1, 6 h day-1) to measure induction of HPRT mutations in lymphocytes from spleen by means of a cloning assay. N-ethyl-N-nitrosourea (ENU) and N-(2-hydroxyethyl)-N-nitrosourea (HOENU) were used as positive controls. Levels of N-(2-hydroxyethyl)valine (HOEtVal) adducts in haemoglobin (expressed in nmol g-1 globin) were measured to determine blood doses of EO (mmol kg-1 h, mM h). Blood doses were used as a common denominator for comparison of mutagenic effects of EO administered via the three routes. The mean HPRT mutant frequency (MF) of the historical control was 4.3 x 10(-6). Maximal mean MFs for ENU (100 mg kg-1) and HOENU (75 mg kg-1) were 243 x 10(-6) and 93 x 10(-6), respectively. In two independent experiments, EO injections led to a statistically significant dose-dependent induction of mutations, with a maximal increase in MF by 2.3-fold over the background. Administration of EO via drinking water gave statistically significant increases of MFs in two independent experiments. Effects were, at most, 2.5-fold above the concurrent control. Finally, inhalation exposure also caused a statistically significant maximal increase in MF by 1.4-fold over the background. Plotting of mutagenicity data (i.e., selected data pertaining to expression times where maximal mutagenic effects were found) for the three exposure routes against blood dose as common denominator indicated that, at equal blood doses, acute i.p. exposure led to higher observed MFs than drinking water treatment, which was more mutagenic than exposure via inhalation. In the injection experiments, there was evidence for a saturation of detoxification processes at the highest doses. This was not seen after subchronic administration of EO. The resulting HPRT mutagenicity data suggest that EO is a relatively weak mutagen in T-lymphocytes of rats following exposure(s) by i.p. injection, in drinking water or by inhalation.

Administration, Inhalation↗

PubMed1999

Short-term exposure of rodents to diesel exhausts: usefulness for studies of genotoxic and immunotoxic effects.

An exposure facility was tested with regard to the information obtainable from short-term animal experiments for the assessment of health hazards from automotive engine exhausts. Indicators of immunotoxicity and genotoxicity were studied in guinea pigs and mice, respectively, exposed for 2 weeks, 8 h/day, to ten times diluted exhausts from a one-cylinder research diesel engine running at constant load. Regulated and non-regulated pollutants were determined. Besides increased number of lavageable cells in the airways, exposed guinea pigs exhibited, after immunization and challenge to ovalbumin, reduced leukotrienes B4 and C4 in lavage fluid and reduced anti-ovalbumin IgG in serum. Absence of increased CYP1A activity indicated that the exposure was below the threshold for induction of these enzymes. Instead a certain reduction of this activity indicated interaction with active enzyme sites. In vivo doses of some reactive metabolites of low molecular mass were measured by adducts to hemoglobin. Doses from aliphatic epoxides were low, in accordance with low hydrocarbon levels in the exhaust. The levels of hemoglobin adducts from aldehydes showed no clearcut influences of exposure. Genetic effects determined by DNA fingerprint analysis were indicated. It is concluded that repeated dose inhalation exposure of small numbers of animals is a useful mode of exposure for studying parameters that may elucidate toxic effects of air pollutants emitted from automotive engines, with a possibility to evaluate engine and fuel with regard to health hazards.

Administration, Inhalation↗

PubMed1999

Effect of lifelong nicotine inhalation on bone mass and mechanical properties in female rat femurs.

As tobacco smoking has been identified as a risk factor in the development of osteoporosis, possible deleterious effects of nicotine inhalation on bone mineral density (BMD) and mechanical properties of the femur in female rats were studied. Female Sprague Dawley rats were exposed to nicotine vapour 20 hours a day 5 days a week for 2 years. The nicotine concentration in the inhaled air was kept at a level, giving a plasma nicotine concentration exceeding that of heavy smokers. Throughout the study, the nicotine-exposed rats weighed approximately 10% less than the control rats. At the end of the study the rats were anesthesized and blood was collected by heart puncture for determination of nicotine in plasma. Both femurs were resected and scanned by dual X-ray absorptiometry (DXA). There was no difference in BMD between control rats (n = 7) and nicotine-exposed rats (n = 23) (mean 0.216 +/- 0.021 g/cm(2) and 0. 210 +/- 0.014 g/cm(2), respectively (P = 0.19)). The left femur was used for mechanical testing of the shaft and the neck. No significant difference could be demonstrated in ultimate bending moment, ultimate energy absorbtion, stiffness, or deflection between the two groups. In conclusion, no negative effects of nicotine inhalation on the femurs of female rats were found.

Absorptiometry, Photon↗

PubMed1998

Metabolic interaction of n-hexane and methyl ethyl ketone in vitro in a head space rat liver S9 vial equilibration system.

Methyl ethyl ketone pretreatment induced rat liver cytochrome P450 and increased significantly the in vitro metabolism of n-hexane and the formation of 2,5-hexanedione in rat liver S9. No significant changes were, however, found in the levels of the intermediate metabolites 2-hexanol, 2,5-hexanediol or methyl n-butyl ketone. Methyl ethyl ketone added in vitro to untreated (non-induced) liver S9 inhibited in a non-competitive pattern the metabolism of n-hexane and decreased significantly and in a dose-dependent way the levels of methyl n-butyl ketone and 2,5-hexanedione. When methyl ethyl ketone and n-hexane were added in vitro to in vivo methyl ethyl ketone pretreated (induced liver S9, the significant increase in the formation of 2,5-hexanedione was maintained, an increase which was only to a minor extent influenced by the in vitro addition of methyl ethyl ketone. These findings are in agreement with an in vivo induction by methyl ethyl ketone of key enzyme(s) in a generally minor metabolic pathway for the conversion of n-hexane to 2,5-hexanedione in rat liver, a pathway which is not influenced by the presence of methyl ethyl ketone itself. The results obtained in this study indicate that the head space equilibration technique is well suited for screening studies of metabolic interactions between organic solvents.

Animals↗

PubMed1998

Optimization and application of the head space liver S9 equilibration technique for metabolic studies of organic solvents.

A head space liver S9 vial equilibration technique for qualitative and quantitative metabolism of volatile organic solvents in vitro is described and investigated for optimal experimental conditions with toluene and n-hexane as model substrates. The method was also used for studying the metabolic interaction between acetone and styrene. NADP+ was a critical cofactor in the system as concentrations above 2.5 mM resulted in inhibition of metabolism. Induction of cytochrome P450 by phenobarbital did not alter the observed cofactor dependency, and addition of vehicles such as rat blood did not enhance metabolism. Acetone-induced liver S9 increased the primary oxidation of styrene and also the formation of styrene oxide, but not significantly that of mandelic acid. Acetone as such had no effect on the metabolic elimination of styrene, indicating that the interaction is mainly on the level of enzyme induction occurring after long-term exposure to acetone. As earlier reports on styrene metabolism in vivo has not been able to detect styrene oxide in toxicokinetic studies with a sufficient degree of accuracy, the head space liver S9 vial equilibration technique may offer a fast and sensitive tool for screening of metabolic interactions between organic solvents when optimized for metabolic activity.

Acetone↗

PubMed1998

Allometric species comparison of toluene and n-hexane metabolism: prediction of hepatic clearance in man from experiments with rodent liver S9 in a head space vial equilibration system.

The liver S9 head space vial equilibration technique is an in vitro alternative that holds promises for a satisfactory in vivo extrapolation of liver metabolism of volatile organic chemicals. The aim of this study was to investigate the suitability of this methodology for the extrapolation of in vitro metabolic data from rodent to man by allometry with the two highly metabolized organic solvents toluene and n-hexane as model substances. The calculated hepatic clearance of toluene in man from rodent liver S9 in this study was equal to the reported total body clearance of toluene in man, suggesting insignificant extrahepatic clearance of toluene in humans. The calculated hepatic clearance of n-hexane was less than the reported values of total body clearance of n-hexane in man, indicating an about 80% extrahepatic clearance of n-hexane in humans. Both results are in line with our present knowledge of the metabolism of the two organic solvents in man. Allometric scaling from rodent liver S9 head space incubations to in vivo metabolism of toluene and n-hexane in man thus seems promising and could be a method of choice for scaling of organic solvent metabolism in general.

Adult↗

PubMed1998

In vitro screening for metabolic interactions among frequently occurring binary mixtures of volatile organic chemicals in Norwegian occupational atmosphere.

Surveys of Norwegian industrial occupational atmosphere between 1983 to 1996, have identified the 12 most frequent occurring binary combinations of volatile organic chemicals. These combinations were tested in vitro for mutual inhibition or enhancement of metabolism by the head space vial equilibration technique with liver S9 obtained from in vivo untreated or pretreated (with the binary mixture) rats. The in vitro system responded to in vivo pretreatment by increasing the metabolic rate of several potentially toxic organic chemicals such as toluene, xylene, styrene, and dichloromethane. In untreated liver S9, the metabolism of several of the tested binary pairs was inhibited when coexposed in vitro to their most prevalent follower as shown for instance for ethanol (with ethyl acetate), dichloromethane (with styrene) and mutually between toluene and xylene. This inhibitory effect disappeared, however, for several of the solvents when combined with the in vivo induced liver S9, a situation which may be the most relevant for occupational exposure. It is concluded that several metabolic interactions occur between low-molecular weight volatile chemicals found in occupational air. These are both inductive and inhibitory in nature and a further mechanistic evaluation including a higher number of differentiated dosage levels, must be performed before a possible health hazard can be confirmed or rejected for the investigated combinations.

Air Pollutants, Occupational↗

PubMed1997

Comparison and in vivo relevance of two different in vitro head space metabolic systems: liver S9 and liver slices.

In vitro systems of high biological organization, e.g. containing intact hepatocytes, have been considered as more reliable for metabolic studies and in vivo predictions of toxicokinetics than subcellular systems. For this reason, the kinetics and metabolism of low-molecular-weight volatile chemicals, i.e. head space elimination of substrate and formation of metabolites, were compared in liver S9 and in liver slices. Two substrates, toluene and n-hexane, were used as they represent differences in metabolic pathways and physical-chemical properties. The two systems responded similarly to diethyldithiocarbamate inhibition and acetone inhibition/induction of cytochrome P-450 mediated metabolism. In contrast to liver S9, liver slices did not respond adequately to phenobarbital induction raising the question of substrate availability for P-450 enzymes in liver slices. Liver slices appeared to be superior to liver S9 when specific metabolic pathways involving phase II enzymes were investigated. However, liver S9 seemed to be at least as good as liver slices for estimation of total metabolic rate constants (Km, Vmax) as a basis for in vivo predictions. As the head space liver S9 system is faster and easier to operate than liver slices, it is a promising screening tool for the metabolism of volatile compounds and metabolic interactions.

Acetone↗

PubMed1997

Accumulation of nicotine in human hair during long-term controlled exposure to a low concentration of nicotine vapour.

Hair from 5 subjects were exposed in dynamic exposure chambers to air nicotine vapour for 72 hr or 12 months at concentrations of 200 or 5 micrograms/m3, respectively. Nicotine in the chamber air and human hair was determined by GC/ MS. A linear accumulation of nicotine in hair was found with time for all hairs during the long-term, low concentration exposure, with individual hair nicotine uptake rate constants ranging from 0.70 to 3.75 x 10(-3) m3/g x hr. The corresponding hair nicotine uptake rate constants during short-term, high concentration exposure, were significantly higher, ranging from 1.35 to 15.11 x 10(-3) m3/g x hr, showing, however, a highly significant linear correlation with the individual long-term exposure rate constants, r2 = 0.9961. It is indicated that long-term hair nicotine uptake rate constants calculated from controlled exposure experiments with pure nicotine vapour are adequate for estimation of individual long-term hair accumulation of nicotine from environmental tobacco smoke even at variable and intermittent exposure. Although higher than the long-term uptake rate constants, the short-term uptake rate constants seem well fitted for a differentiation between different types of hair in their ability to adsorb nicotine also during long-term exposures. The short-term uptake rate constants might also be useful parameters for establishing a reliable cut-off limit in the hair concentration of nicotine between smokers and non-smokers which otherwise seems to be overlapping.

Adolescent↗

PubMed1996

Long-term effects of inhaled nicotine.

Tobacco smoking has been reported to be associated with increased risk of cardiovascular disease and cancer, particularly of the lungs. In spite of extensive research on the health effects of tobacco smoking, the substances in tobacco smoke exerting these negative health effects are not completely known. Nicotine is the substance giving the subjective pleasure of smoking as well as inducing addiction. For the first time we report the effect on the rat of long-term (two years) inhalation of nicotine. The rats breathed in a chamber with nicotine at a concentration giving twice the plasma concentration found in heavy smokers. Nicotine was given for 20 h a day, five days a week during a two-year period. We could not find any increase in mortality, in atherosclerosis or frequency of tumors in these rats compared with controls. Particularly, there was no microscopic or macroscopic lung tumors nor any increase in pulmonary neuroendocrine cells. Throughout the study, however, the body weight of the nicotine exposed rats was reduced as compared with controls. In conclusion, our study does not indicate any harmful effect of nicotine when given in its pure form by inhalation.

Administration, Inhalation↗

PubMed1996

Interindividual differences in hair uptake of air nicotine and significance of cigarette counting for estimation of environmental tobacco smoke exposure.

Hair from 80 male subjects, smokers and non-smokers, was exposed continuously in a dynamic exposure chamber to constant nicotine vapour concentrations of 20, 200 or 2000 micrograms/m3 for 72 hr. Subgroups of high and low nicotine adsorbing hair were also exposed intermittantly to environmental tobacco smoke for 8 months. Air and hair concentrations of nicotine were determined by gas chromatography/mass spectrometry. The chamber experiments demonstrated a hair nicotine uptake which followed a second order relation to the applied concentrations of nicotine, y = -0.00018x2 + 0.715x + 1.13, r2 = 0.99999. The function and the experimental points showed linearity up to an air nicotine vapour concentration of about 200 micrograms/m+, covering the most relevant range of environmental exposure. An approximately 7- and 2-fold interindividual variation was observed in the hair uptake rate constant of nicotine vapour for the investigated material within the 10 to 90 and 25 to 75% percentiles, respectively. The factors causing this variation were not identified. It was shown that subject age, hair diameter and hair content of eumelanin were without correlation to the rate constants of hair nicotine uptake. The exposure of subgroups of hair to environmental tobacco smoke showed similar uptake profiles of nicotine as that experienced with exposure to pure nicotine vapour, supporting the relevance of controlled chamber nicotine vapour exposures as a relevant tool for the evaluation of hair nicotine uptake from a more complex environmental situation. Standardized measurements of air nicotine vapour and particulate concentrations in a modern office during 3 hr periodical smoking periods, showed that the number of cigarettes smoked was a poor indicator for the estimation of individual exposure to environmental tobacco smoke constituents. Hair nicotine measurements so far seem to be superior to other suggested methodologies for estimation of environmental tobacco smoke exposure, but further studies should be initiated to identify factors determining the rate constant of hair nicotine uptake.

Adolescent↗

PubMed1995

Pharmacokinetics of macrolides. Comparison of plasma, tissue and free concentrations with special reference to roxithromycin.

When macrolide antibiotics are administered according to the standard therapeutic regimens, the highest plasma concentrations of total drug, both during the first dosage interval and at steady state, are obtained with roxithromycin, followed by clarithromycin and azithromycin. The corresponding free plasma concentrations, calculated from published data on plasma protein binding for the three macrolides, are of the same order of magnitude and the highest values are again those of roxithromycin. With the use of improved analytical methodology, a stable and prolonged total elimination half-life of roxithromycin of about 19 h was demonstrated at steady state in healthy adults with a 300 mg once daily dosage regimen. Intra-group subject variations (adults, children, the elderly etc.) were smaller than anticipated. Roxithromycin is found in high and similar concentrations both in plasma and tissue, demonstrating a balanced pharmacokinetic behaviour.

Adult↗

PubMed1995

Comparison of three methods for estimating environmental tobacco smoke exposure among children aged between 12 and 36 months.

BACKGROUND: The methods currently used for measuring environmental tobacco smoke (ETS) exposure among small children all have their limitations. The aim of this study was to compare the results of questionnaire assessments of children's ETS exposure with cotinine measurements in urine and nicotine measurements in hair, a new method for estimating average ETS exposure. METHODS: Questionnaire information on ETS exposure and a sample of hair were collected from 94 children aged 12-36 months. A urine sample for cotinine analysis was obtained from 72 of the children. RESULTS: Nicotine was found in all hair samples and cotinine in all urine samples. Compared to children registered as unexposed by the questionnaire, hair nicotine levels were 12.4 times higher among children exposed to more than 10 DNC (daily number of cigarettes) (P < 0.001) and 3.6 times higher among children exposed to 1-10 DNC (P < 0.001). The median cotinine creatinine ratio (CCR) was 2.4 times higher among children exposed to more than 10 DNC compared to unexposed children (P < 0.001). No significant difference in median CCR was found between unexposed children and children exposed to 1-10 DNC. The correlation coefficient was 0.64 between children's hair nicotine levels and DNC, 0.50 between CCR and DNC and 0.56 between children's hair nicotine levels and CCR. CONCLUSION: Nicotine measurement in hair is a practical and valid method for estimating average ETS exposure in children. An underreporting of ETS exposure was indicated.

Age Factors↗

PubMed1994

Clinical pharmacokinetics of tenoxicam.

Tenoxicam is a nonsteroidal anti-inflammatory drug (NSAID) in the oxicam group. It is completely absorbed by the oral route and is about 99% protein bound in human plasma. Intake of food delays absorption without affecting bioavailability. There is no evidence for enterohepatic recycling of the drug in humans. Peak plasma concentrations of 2.7 mg/L (range 2.3 to 3.0 mg/L) have been reported in different groups of fasted healthy volunteers 1.9 hours (1.0 to 5.0 hours) after a single oral dose of 20mg. A mean elimination half-life of 67 hours (49 to 81 hours) has been estimated. Tenoxicam demonstrates linear single-dose pharmacokinetics over doses of 10 to 100mg. Because of its low lipophilicity and high degree of ionisation in blood (approximately 99%), the drug is poorly distributed to body tissues and is slowly taken up by hepatic cells. A small apparent volume of distribution of 9.6L (7.5 to 11.5L), and low total plasma clearance of 0.106 L/h (0.079 to 0.142 L/h), have been reported in different groups of healthy volunteers after oral and intravenous administration. Peak concentrations of tenoxicam in synovial fluid are less than one-third of those in plasma and they appear later, 20 hours (10 to 34 hours) after an oral dose. A parallel decrease in synovial fluid and plasma concentrations with time for both total and unbound tenoxicam has been reported. In vivo pH differences between synovial fluid and plasma in patients with rheumatoid arthritis may indicate significantly lower concentrations of unbound ionised tenoxicam in synovial fluid than in plasma. Data on relative binding capacities for tenoxicam in plasma and synovial fluid, and between different groups of individuals, are not conclusive. The protein binding of tenoxicam is pH dependent. The drug is almost entirely eliminated by liver metabolism. The 2 main metabolites, the inactive 5'-hydroxy and 6-O-glucuronidated forms, are excreted in urine and bile, respectively. The existence of additional metabolites in human bile has been suggested. Urinary excretion of the 5'-hydroxy metabolite decreases with reduced renal function. The 5'-hydroxy metabolite is detected in plasma in concentrations 1 to 5% of the parent compound and its decline parallels that of the parent compound (formation-rate limitation). Urinary and faecal excretion of unchanged tenoxicam is less than 1% of the administered dose. No significant amounts of unchanged tenoxicam are excreted in bile. Tenoxicam shows nearly linear pharmacokinetics during multiple-dose administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Drug Interactions↗

PubMed1993

Effect of nicotine on the enterochromaffin like cells of the oxyntic mucosa of the rat.

Smoking has an unfavourable effect on peptic ulcer disease. The pathophysiological mechanisms underlying this effect are not known. The enterochromaffin like (ECL) cell is the cellular source of histamine participating in the regulation of acid secretion. The ECL cell is under functional and trophic control of gastrin and the vagus nerves. Nicotine may affect acid secretion through vagal pathways. Furthermore, nicotine may also stimulate neuroendocrine cells. The present study examined if chronic nicotine administration could stimulate the function and growth of the ECL cell. Rats inhaled nicotine vapour at a concentration of approximately 6.2 mumol/m3, 20 hours/day, 5 days/week for 11 weeks. Steady state plasma nicotine concentration was 461.8 (137.5 (SD)) nmol/l. The ECL cell density, histamine content and histidine decarboxylase activity of the oxynitic mucosa were similar to the controls. We also examined the effect of acute nicotine stimulation on the acid output and histamine release from the totally isolated vascularly perfused rat stomach. Nicotine did not stimulate acid secretion or histamine release. Thus no evidence could be provided to support the hypothesis that nicotine exerts its negative effects on peptic ulcer disease by stimulating the ECL cell.

Administration, Inhalation↗

PubMed1993

Inhalation kinetics of C8 to C10 1-alkenes and iso-alkanes in the rat after repeated exposures.

The toxicokinetic properties of C8 and C10 1-alkenes and iso-alkanes 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 in blood, brain, liver, kidneys and perirenal fat at days 1, 2 and 3, immediately after exposure and 12 hr after exposure on day 3. The 1-alkenes showed an efficient absorption to blood combined with extensive accumulation in organs, compared to the iso-alkanes. The concentration of 1-alkenes and iso-alkanes in blood, brain, liver and fat increased with increasing number of carbon atoms. The C9 and C10 1-alkenes and iso-alkanes showed increasing concentration in fat during the exposure period and high concentrations 12 hr after cessation of exposure. The extensive accumulation in both blood and organs of 1-alkenes compared to any of the other groups of hydrocarbons may have a toxicologic relevance. Products which contain 1-alkenes should be handled carefully to minimize the risk of inhalation exposure.

Absorption↗