Johannes Konietzko

Elimination of polychlorinated dibenzo-p-dioxins and dibenzofurans in occupationally exposed persons

The elimination of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) was investigated in a group of n = 43 exposed workers with 2 blood measurements and n = 5 workers with 3 measurements. Under the assumption of a one-compartment, first-order kinetic model the median half-life for 2,3,7,8-TCDD was 7.2 yr, while for the other dioxins the estimates were between 3.7 yr for 1,2,3,4,6,7,8-HpCDD (hepta-chlorinated) and 15.7 yr for 1,2,3,7,8-PCDD (penta-chlorinated). For the furans median half-lives between 3.0 yr for 1,2,3,4,6,7,8-HpCDF and 19.6 yr for 2,3,4,7,8-PCDF were observed. There was no indication for a deviation from a first-order kinetic. Increasing age and percent body fat were associated with increasing half-life for most of the congeners. Smokers in general had a faster decay than non- and ex-smokers. In summary, the higher chlorinated PCDD/F like TCDD appear to be highly persistent in humans with half-lives ranging between 4 and 12 yr.

DNA damage in nurses handling antineoplastic agents

In 91 nurses from several divisions of four hospitals in Germany the genotoxic effect caused by the occupational exposure presumably due to mixing of antineoplastic agents was investigated. The amount of DNA single strand breaks and alkali labile sites in the peripheral mononuclear blood cells of the nurses was measured using the alkaline elution method. In ten nurses handling antineoplastic agents not using recommended safety precautions such as safety hoods, gloves or surgical masks a 50% higher level of DNA strand breaks and alkali-labile sites (p < 0.005; U-test) was detected compared to 54 controls. After applying recommended safety precautions a statistically significant decrease (p < 0.01) in the level of DNA strand breaks to the level of controls was observed. In other nurses handling antineoplastic agents by using adequate safety equipment no significantly different amount of DNA strand breaks compared to that of controls was detected. No significant correlation between the level of DNA strand breaks and the weekly contact frequency, the life-time exposure to antineoplastic agents, or the time elapsed since the last handling of the drugs was found in this study.

ELIMINATION OF β-HEXACHLOROCYCLOHEXANE IN OCCUPATIONALLY EXPOSED PERSONS

Abstract The elimination offi-hexachlorocyclohexane (

Effects of high doses of toluene on color vision.

-HCH) in humans was investigated in a group of 40 former workers of a lindane-producing plant by analyzing at least 2 blood specimens (3 specimens in 3 workers) from different time points. Assuming a first-order kinetic model for excretion, the median half-life of

Exposure to 200 ppm of methanol increases the concentrations of interleukin-1β and interleukin-8 in nasal secretions of healthy volunteers

-HCH is 7.2 yr calculated by concentrations in whole blood and 7.6 yr calculated by concentrations in extractable lipids. In univariate analyses an influence of age, percent body fat, and liver disease (additionally in whole blood an influence of contents of extractable lipids) on clearance was observed. All factors show a positive correlation with half-life. According to a multiple regression model, influence of percent body fat calculated according to Deurenberg et al. (1991) is an important covariate in the description of the variations of the clearance rate (calculated on the basis of extractable lipids) of

Porphyrin studies in TCDD-exposed workers

-HCH. The data support the assumption of first-order kinetics.

Acute effects of 1,1,1-trichloroethane on human olfactory functioning.

High exposure to toluene may cause optic neuropathy and retinopathy, both associated with dyschromatopsia. Another solvent, ethanol, is known to induce acute blue-yellow dyschromatopsia. This study investigated the acute effects of high doses of toluene on color vision. Eight male printshop workers were examined before and after cleaning printing containers with pure toluene. After cleaning, concentrations of toluene in blood were between 3.61 and 7.37 mg/l. Color vision was tested with the Farnsworth panel D-15 test, the Lanthony desaturated panel D-15 test, and the Standard Pseudoisochromatic Plates part 2. For control of possible acute effects, eight workers of a metal-working factory without any neurotoxic exposure were tested according to the same procedure. Acute exposure to toluene did not cause impairment of color vision. However, statistical power is limited due to the small number of exposed subjects. Color vision of the printshop workers tested before cleaning was slightly impaired (statistically not significant) when compared with unexposed subjects.

Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

This study was designed to investigate subclinical irritating effects of methanol on functional and immunologic parameters in human respiratory epithelia. Twelve healthy, nonsmoking individuals were exposed to concentrations of 20 and 200 ppm of methanol in an exposure chamber. The concentrations of interleukin (IL)-8, IL-1β, IL-6, and prostaglandin E2 (PGE2) were monitored. The saccharin transport time test was used to evaluate mucociliary transport. Video interference contrast microscopy was used to determine the ciliary beat frequency of nasal epithelial cells. Subjective symptoms were assessed with a questionnaire. The median concentrations of IL-8 and IL-1β were significantly elevated after exposure to 200 ppm of methanol as compared to exposure to 20 ppm (IL-1β, 21.4 versus 8.3 pg/mL, p = .001; IL-8, 424 versus 356 pg/mL, p = .02). The release of IL-6 and PGE2 did not change significantly (IL-6, 10.3 versus 6.5 pg/mL, p = .13; PGE2, 13.6 versus 13.4 pg/mL), nor did the ciliary beat frequency or the saccharin transport time. Both IL-8 and IL-1β proved to be sensitive indicators for subclinical irritating effects of methanol in vivo. The German threshold limit of 200 ppm of methanol does not prevent subclinical inflammatory reactions of the nasal respiratory mucosa.

Blue-yellow deficiency in workers exposed to low concentrations of organic solvents

Abstract2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to inhibit uroporphyrinogen decarboxylase activity resulting in chronic hepatic porphyria. From a cross-sectional study of 170 workers in chemical industry 68 showed elevated coproporphyrin levels, interpreted as secondary coproporphyrinuria. Three persons suffered from chronic hepatic porphyria in subclinical stages. None of the workers showed an overt porphyria cutanea tarda. A lowgrade zinc protoporphyrinemia was observed in three persons. Forty-three of the 170 workers were evaluable for investigating the effect of TCDD on porphyrin levels. No significant correlation was found between TCDD concentration in adipose tissue and the level of uroporphyrin and coproporphyrin. The influence of a chloracne history is described.

The exposure of healthy volunteers to 200 ppm 1,1,1-trichloroethane increases the concentration of proinflammatory cytokines in nasal secretions

Background Animal experiments indicate that 1,1,1-trichloroethane can cause degeneration of the olfactory epithelium. The effects of 1,1,1-trichloroethane on human odor perception still have not been investigated. The goal of this study was to learn more about acute effects of 1,1,1-trichloroethane. Methods Twelve healthy, nonsmoking students were exposed to 200 and 20 ppm (control) 1,1,1-trichloroethane in an exposure chamber for 4 hours according to a crossover design. Olfactory functioning was investigated with the Sniffin’ Sticks. The test includes the determination of the detection threshold for n-butanol and an odor identification test. Results After 1 hour of exposure to 200 ppm 1,1,1-trichloroethane, no effects on olfactory functioning were observed. After 4 hours, the olfactory threshold for n-butanol was slightly (p = 0.04) elevated. Conclusion The threshold shift may be caused by different mechanisms, including inflammation of the olfactory mucosa or degeneration of receptor cells.