Nonlinear changes in the activity of the oxygen-dependent demethylase system in Rhodococcus erythropolis cells in the presence of low and very low doses of formaldehyde

The effect of exogenous, highly diluted formaldehyde on the rate of demethylation/re-methylation of veratric acid by the bacteria Rhodococcus erythropolis was studied using electrophoretic and microscopic techniques. The activity of 4-O-demethylase, responsible for accumulation of vanillic acid, and the levels of veratric and vanillic acids were determined using capillary electrophoresis. Formaldehyde was serially diluted at 1:100 ratios, and the total number of iterations was 20. After incubation of the successive dilutions of formaldehyde with the bacteria, demethylase activity oscillated in a sinusoidal manner. It was established using capillary electrophoresis that methylation of vanillic acid to veratric acid occurred at a double rate, as shown by the doubled fluctuation in the concentration of veratrate. There were also changes in the NADH oxidase activity, which is associated with methylation processes. Microscopic observations revealed the presence of numerous enlarged vacuoles in bacterial cells during the accumulation of large amounts of vanillic acid, and their disappearance together with a decrease in 4-O-demethylase activity. The presented results give evidence for the ability of living cells to detect the presence of submolecular concentrations of biological effectors in their environment and provide a basis for a scientific explanation of the law of hormesis and the therapeutic effect of homeopathic dilutions

Granica izlaganja formaldehidu u alkoholnim pićima

Formaldehyde has been classified as carcinogenic to humans (WHO IARC group 1). It causes leukaemia and nasopharyngeal cancer, and was described to regularly occur in alcoholic beverages. However, its risk associated with consumption of alcohol has not been systematically studied, so this study will provide the first risk assessment of formaldehyde for consumers of alcoholic beverages. Human dietary intake of formaldehyde via alcoholic beverages in the European Union was estimated based on WHO alcohol consumption data and literature on formaldehyde contents of different beverage groups (beer, wine, spirits, and unrecorded alcohol). The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses (BMD) for 10 % effect obtained from dose-response modelling of animal experiments. For tumours in male rats, a BMD of 30 mg kg-1 body weight per day and a “BMD lower confi dence limit” (BMDL) of 23 mg kg-1 d-1 were calculated from available long-term animal experiments. The average human exposure to formaldehyde from alcoholic beverages was estimated at 8·10-5 mg kg-1 d-1. Comparing the human exposure with BMDL, the resulting MOE was above 200,000 for average scenarios. Even in the worst-case scenarios, the MOE was never below 10,000, which is considered to be the threshold for public health concerns. The risk assessment shows that the cancer risk from formaldehyde to the alcohol-consuming population is negligible and the priority for risk management (e.g. to reduce the contamination) is very low. The major risk in alcoholic beverages derives from ethanol and acetaldehyde.Formaldehid je kancerogen za ljude te je klasificiran u skupinu 1 prema WHO IARC-u. Uzrokuje leukemiju i nazofaringealni karcinom, a navodi se i kao redoviti sastojak alkoholnih pića. Međutim, rizik od izlaganja formaldehidu konzumacijom alkoholnih pića nije sustavno istražen pa će ovo istraživanje pružiti prvu takvu procjenu rizika. Količina formaldehida koju ljudi unose alkoholnim pićima u Europskoj je uniji procijenjena temeljem podataka Svjetske zdravstvene organizacije o konzumaciji alkohola i literature o sadržaju formaldehida u različitim skupinama alkoholnih pića (pivo, vino, jaka alkoholna pića i neregistrirani alkohol). Procjena rizika obavljena je korištenjem pristupa granice izlaganja (eng. margin of exposure, MOE) i graničnih doza (eng. benchmark doses, BMD) za 10 %-tni učinak koji se postiže modeliranjem odnosa doza-odgovor u ispitivanjima provedenima na životinjama. BMD od 30 mg kg-1 tjelesne težine na dan i BMD s nižom granicom pouzdanosti (BMDL) od 23 mg kg-1 d-1 izračunati su za tumore kod mužjaka štakora temeljem raspoloživih dugotrajnih ispitivanja provedenih na životinjama. Prosječno izlaganje ljudi formaldehidu u alkoholnim pićima procijenjeno je na 8·10-5 mg kg-1 d-1. U usporedbi s BMDL vrijednošću krajnji MOE je iznosio više od 200.000 u prosječnim situacijama. Čak i u najlošijim situacijama MOE nije nikada bio niži od 10.000, što se smatra graničnom vrijednošću za zdravlje ljudi. Procjena rizika pokazuje da je rizik od nastanka karcinoma uslijed izlaganja formaldehidu iz alkoholnih pića zanemariv te da je prioritet upravljanja rizikom u takvim slučajevima (npr. kako bi se smanjila kontaminacija) vrlo nizak. Najveći rizik proizlazi iz etanola i acetaldehida koji se također nalaze u alkoholnim pićima