Dottorato in Scienze Farmaceutiche e Biomolecolari

Contacts

Supervisor

Phd thesis

Monitoring and Prevention of Formaldehyde in Life and Work Environments: biological effects of formaldehyde on proteins, DNA, and oxidative stress status.

The physic-chemical properties of FA and its toxicological and carcinogenic properties make this gas an important risk factor for human health, both in the occupational and in the life environments, and both by inhalation and by contact. For these reasons exists a Ceiling limit specific for FA exposure, valid in the occupational environments and for all works that use FA (0.3 ppm = 0.37 mg/m³). In relation to the presence of FA in living and working environments, the multiplicity of its many industrial uses and the possibility of exposure in some works, it was decided to start an intensive biomonitoring activity that would put light on some aspects related to the exposure in working and life environments to this gas. In some cases, the use of FA is currently unavoidable, for its remarkable properties of strong fixative, preserving tissues and bactericidal agent, which often makes it a product so far irreplaceable.

As mentioned before, exposure to FA can cause alteration of some biological parameters that can be used to identify the real extent of exposure (eg. N-methylenvaline, or specific DNA damages), and the individual risk for an exposed person, assuming that the detected alterations at cellular, biochemical, and at DNA level could be highly correlated – firstly with environmental level of FA - and secondly with an increased risk of mutation and subsequent transformation of the affected cell towards neoplastic direction.

The physiological levels of these biomarkers of exposure and/or risk might be modulated not only by the exposure, but also by other factors, such as the enzymatic detoxification of metabolic processes, and the capacity to repair DNA damages. Thus, the identification of a relationship between the levels of exposure to FA and the possible altered levels of this biomarkers could provide a valuable tool for primary prevention.

The EU directives have set the standard exposure level for both the workplace and for the general population. However, at the present state of knowledge on carcinogenic properties of FA, we can not exclude effects due to exposure to even minimal concentrations of FA, thus we recently planned some environmental and biological samplings also enrolling groups exposed to environmental concentration of FA, such as children, who are biologically more sensitive.

The work of research lasted these 3 years has been aimed at identifying biomarkers of exposure and effect that could be predictive of the risk from exposure to FA in urban environments, with different degrees of pollution. In particular, biomonitoring studies of populations exposed to medium-low concentrations of environmental FA did not always have shown a clear dose-effect relationship, probably because of the difficulty in defining one singular  environmental exposure. Thus, there is a need for a systematic study that takes into account the real environmental exposure to FA, to correlate it with appropriate biomarkers.

Up to now this study has involved people with different levels of exposure to FA, selected through standard epidemiological criteria: subjects exposed to medium-high concentrations of FA chosen among occupational areas for which is used this substance (pathologist and workers in industries of plastic laminates), and subjects exposed to low concentrations of FA (adults and children from the general population).

The experimental design involved a series of biomarkers for each experimental endpoint investigated: the M₁dG DNA adduct quantified on peripheral blood lymphocytes as an indicator of a genotoxic effect of exposure to FA, the 15F_2t urinary Isop, as first experimental evidence of alterated oxidative status after exposure to FA, and N-Methylenvaline as  an indicator of an effect on proteins.

The obtained results will allow to quantify the extent of the endpoints investigated, in relation to various levels of exposure to FA, which finally could differently contribute to an increased risk of cancer. In general we have started a biomonitoring activity among people occupationally exposed to FA, with high level of this gas, to better highlight which were the endpoints to reach; then we have proceeded with samplings among a children population, to verify a possible biological effect  also at this low concentration of FA.