Exposure study to examine chemosensory effects of formaldehyde on hyposensitive and hypersensitive males.

OBJECTIVE: Main objective of this study was to examine the chemosensory effects of formaldehyde on hyposensitive and hypersensitive males at concentrations relevant to the workplace. Attention focused on objective effects on and subjective symptoms of the mucous membranes of the eyes, the nose, the upper respiratory tract and olfactory function. METHODS: Forty-one male volunteers were exposed for 5 days (4 h per day) in a randomised schedule to the control condition (0 ppm) and to formaldehyde concentrations of 0.5 and 0.7 ppm and to 0.3 ppm with peak exposures of 0.6 ppm, and to 0.4 ppm with peak exposures of 0.8 ppm, respectively. Peak exposures were carried out four times a day over a 15-min period of time. Subjective pain perception induced by nasal application of carbon dioxide served as indicator for sensitivity to sensory nasal irritation. The following parameters were examined before and after exposure: subjective rating of symptoms and complaints (Swedish Performance Evaluation System), conjunctival redness, eye-blinking frequency, self-reported tear film break-up time and nasal flow rates. In addition, the influence of personality factors on the volunteer's subjective scoring was examined (Positive And Negative Affect Schedule). RESULTS: Formaldehyde exposures to 0.7 ppm for 4 h and to 0.4 ppm for 4 h with peaks of 0.8 ppm for 15 min caused no significant sensory irritation of the measured conjunctival and nasal parameters. No differences between hypo- and hypersensitive subjects were seen. Nevertheless, statistically significant differences were noted for olfactory symptoms, especially for the 'perception of impure air'. These subjective complaints were more pronounced in hypersensitive subjects. CONCLUSIONS: Formaldehyde concentrations of 0.7 ppm for 4 h and of 0.4 ppm for 4 h with peaks of 0.8 ppm for 15 min did not cause adverse effects related to irritation, and no differences between hypo- and hypersensitive subjects were observed.

Is individual nasal sensitivity related to cellular metabolism of formaldehyde and susceptibility towards formaldehyde-induced genotoxicity?

Forty-one volunteers (male non-smokers, aged 32 ± 9.6yrs) were tested for susceptibility towards unspecific nasal irritation (sensitivity towards CO(2)) in order to define subgroups of hypersensitive and hyposensitive subjects. Blood samples were taken and the expression (mRNA level) of the GSH-dependent formaldehyde dehydrogenase gene (FDH, identical to alcohol dehydrogenase 5, ADH5; EC 1.2.1.46) was measured in leukocytes by quantitative real-time RT-PCR with TaqMan probes. FDH is the most important enzyme for the metabolic inactivation of FA. Blood samples were exposed to 150µM formaldehyde (FA) for 2h and the induction of DNA-protein crosslinks (DPX) in leukocytes was measured by means of a modification of the alkaline comet assay (i.e., by assessing the reduction of DNA migration induced by γ-radiation). Removal of DPX was determined by the abolition of FA-induced reduction in DNA migration within 4h after the end of the exposure. Furthermore, the induction of sister chromatid exchange (SCE) in cultured lymphocytes was studied after treatment of whole blood cultures with FA (150µM). A correlation analysis was performed for all parameters tested for the whole study group and for hypersensitive and hyposensitive subgroups. The results indicate that despite large differences in CO(2)-sensitivity, the susceptibility towards nasal irritation was not related to the induction of genotoxic effects (DPX, SCE) in peripheral blood or to the protection of blood cells against FA-induced effects (expression of FDH, repair capacity for FA-induced DPX). There was no correlation between CO(2)-sensitivity and the expression of FDH. There was also no close correlation between the various indicators of cellular sensitivity towards FA-induced genotoxic effects and no subgroups were identified with particular mutagen sensitivity towards FA.

Assessment of genotoxic effects and changes in gene expression in humans exposed to formaldehyde by inhalation under controlled conditions.

Forty-one volunteers (male non-smokers) were exposed to formaldehyde (FA) vapours for 4 h/day over a period of five working days under strictly controlled conditions. For each exposure day, different exposure concentrations were used in a random order ranging from 0 up to 0.7 p.p.m. At concentrations of 0.3 and 0.4 p.p.m., four peaks of 0.6 or 0.8 p.p.m. for 15 min each were applied. During exposure, subjects had to perform bicycle exercises (∼80 W) four times for 15 min. Blood samples, exfoliated nasal mucosa cells and nasal biopsies were taken before the first and after the last exposure. Nasal epithelial cells were additionally sampled 1, 2 and 3 weeks after the end of the exposure period. The alkaline comet assay, the sister chromatid exchange test and the cytokinesis-block micronucleus test were performed with blood samples. The micronucleus test was also performed with exfoliated nasal mucosa cells. The expression (mRNA level) of the glutathione (GSH)-dependent formaldehyde dehydrogenase (FDH, identical to alcohol dehydrogenase 5; ADH5; EC 1.2.1.46) was measured in blood samples by quantitative real-time reverse transcription-polymerase chain reaction with TaqMan probes. DNA microarray analyses using a full-genome human microarray were performed on blood samples and nasal biopsies of selected subgroups with the highest FA exposure at different days. Under the experimental conditions of this study, inhalation of FA did not lead to genotoxic effects in peripheral blood cells and nasal mucosa and had no effect on the expression of the FDH gene. Inhalation of FA did also not cause alterations in the expression of genes in a microarray analysis with nasal biopsies and peripheral blood cells.