Kaija Pyykkö

Toluene concentrations in various tissues of rats after inhalation and oral administration

The uptake, distribution, and elimination of 3H-toluene in various tissues of rats were studied after inhalation or after gastric intubation.The maximum radioactivity was measured 2–3 h after gastric intubation in tissues, except in white adipose tissue, where the peak radioactivity was reached at 5 h.After inhalation exposure, the uptake to various tissues was very rapid. The maximum radioactivity in most tissues was reached in 15–30 min. The accumulation was slowest in white adipose tissue, where it took 1–2 h.The radioactivity in tissues decreased after inhalation exposure more rapidly than after gastric intubation. Brown adipose tissue and white adipose tissue were different from other tissues in their ability to retain toluene. Twenty-four hours after exposures, only 1% or less of the initial radioactivity was found in tissues other than white adipose tissue, in which the corresponding value was 3.5–5%.The results show a very rapid absorption and distribution of toluene after inhalation and a retention of radioactivity in white adipose tissue. After oral ingestion the distribution showed a similar but much slower pattern.ZusammenfassungNach Inhalation und nach oraler Gabe wurden Aufnahme, Verteilung und Ausscheidung von 3H-Toluol in verschiedenen Geweben der Ratte untersucht.Bei oraler Gabe (mittels Schlundsonde) wurde das Maximum an Radioaktivität im weißen Fettgewebe nach 5 Std erreicht, während es in allen anderen untersuchten Organen bereits nach 2–3 Std auftrat. Nach Inhalation wurde 3H-Toluol wesentlich schneller aufgenommen. Die höchste Radioaktivität wurde hierbei im weißen Fett nach 1–2 Std und in den meisten anderen Geweben nach 15–30 min gemessen. Ebenso war die Abnahme der Radioaktivität nach Inhalation schneller als nach oraler Gabe, wobei sich auch in diesem Fall das braune und das weiße Fettgewebe von anderen Organen unterschieden. Vierundzwanzig Stunden nach Applikation enthielt das Fett noch 3,5–5% der initialen Radioaktivität, während in allen anderen Geweben nur noch 1% oder weniger gemessen wurden.Die Ergebnisse dieser Studie zeigen, daß Toluol nach Inhalation sehr viel rascher absorbiert und wieder ausgeschieden wird, als nach oraler Aufnahme, während das Verteilungsmuster nach beiden Applikationsarten sehr ähnlich ist.

Effects of methylbenzenes on microsomal enzymes in rat liver, kidney and lung

The effects of pretreatment with toluene, o-, m-, p-xylene and mesitylene were investigated on the microsomal enzymes of liver, kidney and lung in rats. The activities of aminopyrine N-demethylase, aryl hydrocarbon hydroxylase, aniline hydroxylase, NADPH-cytochrome c reductase, as well as the concentrations of cytochrome P-450 and cytochrome b5 were determined. The effects were most marked in the liver, where toluene caused increase in aniline hydroxylase and cytochrome P-450; o-xylene in aminopyrine N-demethylase and cytochrome b5; m-xylene and mesitylene in all the enzymes investigated. In kidneys, all the compounds increased the activity of aniline hydroxylase; m-xylene induced cytochrome P-450 and b5 as well as NADPH-cytochrome c reductase; p-xylene induced cytochrome P-450, and mesitylene cytochrome P-450 and b5. Aminopyrine N-demethylase activity was decreased by toluene. In lungs, only mesitylene caused any significant differences from the controls: increase in aminopyrine N-demethylase and aryl hydrocarbon hydroxylase, decrease in aniline hydroxylase. The methylbenzenes tested induced the microsomal enzymes in a rough correlation to the number of their methyl groups and their hydrophobic properties.

Serum 25‐Hydroxyvitamin D Levels in Finnish Children Aged 2 to 17 Years

ABSTRACT. Serum levels of 25‐hydroxyvitamin D (25‐OHD) in summer and winter were studied in 564 children aged 2–17 years living in the northern, central or southern parts of Finland. The mean levels of 25‐OHD were significantly lower in winter (13.3 ± 10.8 ng/ml) than in summer (27.2 ± 10.3 ng/ml) in all age groups (p < 0.001). The mean 25‐OHD levels in the northern part of the country did not differ significantly from the others. In both seasons the levels of 25‐OHD were lower in the 11–17 year age group than in younger children. In that age group 22.4 % of the children had serum levels of 25‐OHD below 5 ng/ml (the limit of risk for rickets), compared to 16.8 % of children 6–10 years old and 7.5 % of children 2–5 years old, but none of the children showed any laboratory evidence of rickets.

Time-course of effects of toluene on microsomal enzymes in rat liver, kidney and lung during and after inhalation exposure☆

Inhalation of toluene vapour of 2000 ppm increased the activities of aniline hydroxylase, aminopyrine N-demethylase, aryl hydrocarbon hydroxylase and NADPH-cytochrome c reductase and the concentrations of cytochromes P-450 and b5 in liver microsomes of adult male rats after an exposure period of 1 day or less. Repeated treatments, 8 h daily for 1-16 days, had only a slight further effect. In lung microsomes, the activities of monooxygenases and the concentration of cytochrome P-450 decreased after 6-24 h toluene exposure, but those of cytochrome b5 and NADPH-cytochrome c reductase did not change. In kidney microsomes the changes were mostly insignificant. After discontinuation of exposure the activities of enzymes and the concentrations of cytochromes returned to the control level in 1-4 days. The results obtained resemble the time-courses for the induction of monooxygenases by other inducers. The tissue differences suggest the unequal distribution of various cytochrome P-450 forms and their individual responsiveness to induction in liver, kidneys and lungs.

Effects of 4 mg estradiol valerianate on serum lipids in newly oophorectomized women.

The material consisted of 32 patients, 12 of whom were selected for control. All were cases approaching the menopause and had been subject to oophorectomia bilateralis and hysterectomia for myomas. All 20 investigation patients received estradiol valerianate orally 4 mg/day of 6 mth. During the course the serum estradiol level increased 5--6-fold from the postmenopausal levels. No significant changes occurred in the serum triglycerides and total cholesterol, whereas in the control group the triglycerides decreased. The proportional concentration of beta-lipoproteins decreased. There was also a slight decrease in the pre-beta-lipoproteins. The proportional concentration of beta-lipoproteins increased, as also serum high density lipoprotein (HDL) cholesterol. In the liver enzymes no changes occurred. Blood pressure increased in one patient. There were no other complications.

Effects of pretreatment with toluene, phenobarbital and 3-methylcholantrene on the in vivo metabolism of toluene and on the excretion of hippuric acid in the rat

The limit of the capacity of male adult Sprague-Dawley rats to metabolize toluene and excrete it as hippuric acid was reached at a dose of 10 mmol toluene/kg. At this dose of benzoic acid or hippuric acid, the excretion of hippuric acid was 1.5-fold and 4-fold, respectively, greater than that following this dose of toluene. When toluene was given after phenobarbital pretreatment the excretion rate of hippuric acid increased 3-4-fold, but 3-methylcholanthrene pretreatment had no effect. Consecutive toluene exposures increased hippuric acid excretion on the third day by about 2-fold. It seems that the side-chain oxidation is the rate-limiting step in toluene metabolism of uninduced rats, and toluene accelerates its own metabolism by inducing cytochrome P-450 dependent microsomal monooxygenases.

Serum oestrone, oestradiol and oestriol levels in ovariectomized women receiving a high dose of oestradiol valerate

Fourteen recently ovariectomized women received 4 mg of oestradiol valerate therapy daily for 6 mth. Serum oestrogens were measured by radioimmunoassay at monthly intervals. The results of therapy produced a 25-fold increase in serum oestrone (E1) concentration. Circulating oestradiol (E2) increased 5-to 6-fold. No accumulation of oestrogens was observed as a consequence of treatment. Serum concentration of oestriol (E3) showed no elevation. One month after the completion of therapy the E1 and E2 concentrations had returned to pre-treatment levels. Although therapy of high-dose oestradiol valerate was well-tolerated, it is not recommended because of the non-physiological high serum concentrations of oestrone and high serum level of oestradiol.