Stereochemical aspects of styrene biotransformation.

Urine of rats dosed with styrene (240 mg/kg), R-, S- and racemic styrene oxide (150 mg/kg) was analysed for mandelic acid enantiomers and for regioisomers and diastereomers of mercapturic acids by NMR spectrometry. Enantiomers of mandelic acid were converted to diastereomeric Mosher's derivatives prior to analysis. R- and S-styrene oxide yielded predominantly R- and S-mandelic acid, respectively, racemic styrene oxide gave predominantly the R-enantiomer whereas styrene yielded almost racemic mandelate. The regioselectivity of mercapturic acid formation was very similar for styrene, R- and S-styrene oxide. These three species yielded a 2:1 mixture of N-acetyl-S-(1-phenyl-2-hydroxyethyl)cysteine (MA1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)cysteine (MA2). R-Styrene oxide gave higher conversion to mercapturic acids (28%) than the S-isomer (19% of the dose). However, R-styrene oxide yielded stereospecifically S,R-MA1 and R,R-MA2 whereas S-styrene oxide gave R,R-MA1 and S,R-MA2. Styrene yielded a mixture of diastereomeric mercapturic acids. The ratios of R,R-/S,R-isomers were 80:20 and 15:85 for MA1 and MA2, respectively. These data suggest that styrene is metabolised stereoselectively to S-styrene oxide as a major enantiomer in rat in vivo. This enantiomer has been reported to be less mutagenic than R-styrene oxide in vitro.

The evidence for conjugated mandelic and phenylglyoxylic acids in the urine of rats dosed with styrene.

Male Wistar rats were dosed intraperitoneally with styrene (400 mg/kg). Urine samples were collected over phosphate buffer, pH 6.5 for 24 h. Excretion of mandelic (MA) and phenylglyoxylic acid (PGA) amounted to 1.66 +/- 0.62 and 5.21 +/- 2.44% of dose, respectively, as determined by ion-pair HPLC. After acidic hydrolysis, the amount of MA and PGA found in urine increased to 2.10 +/- 0.84 and 6.81 +/- 3.20% (mean +/- S.D.; n = 7), respectively. A similar increase was observed after alkaline hydrolysis of urine samples. Differences between hydrolysed and non-hydrolysed samples were significant in the paired t-test (P < 0.05). Further, urine samples were fractionated by HPLC. Fractions were subjected to acidic hydrolysis and analysed by HPLC and GC/MS. Both MA and PGA were detected in the fraction which did not contain any of these metabolites before hydrolytic treatment. Thus, MA and PGA, which are used as biomarkers of exposure to styrene, form hydrolysable conjugates in the rat. At least a minor part of the total urinary MA and PGA is bound in these conjugates.

[Examination of the vocal range in school children]. / Vysetrení hlasového pole u skolních detí.

The author examined in 50 children (pupils of the 1st 50 5th form of primary school), selected at random, the vocal field. The group comprised 22 boys and 28 girls, always 10 children from the same form. Their mean vocal range was 17 semi-tones from G sharp to C2. The maximal dynamic range varied between 10 and 13 dB and did not exceed the intensity of 75 dB A. These results suggest relatively limited dynamics of the singing voice in children and indicate the optimal vocal position and range. Marked transcendence of these limits is probably one of the reasons which lead in some children singing in choirs to overburdening of the vocal organ and may lead to the development of hyperkinetic dysphonia.