Methotrexate – inhalable fraction Documentation of proposed values of occupational exposure limits (OELs)

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Methotrexate – inhalable fraction Documentation of proposed values of occupational exposure limits (OELs)

Journal Title: Podstawy i Metody Oceny Środowiska Pracy - Year 2015, Vol 31, Issue 1

Abstract

Methotrexate (MTX) is a structural analogue of folic acid. This compound is solid at room tem-perature; it is a yellowish-orange, crystalline powder with a slight odor characteristic of aro-matic compounds. Methotrexate is a cytostatic drug administered in infusion or orally; it is a folic acid antagonist.Occupational exposure to cytotoxic drugs takes place at two stages of their application, i.e., during manufacturing processes and during their use in daily practice of medical wards, especially those which treat cancer patients. In Poland, methotrexate is not produced, and there are currently no data on the number of people exposed to its action in health care, be-cause the value of the maximum concentration of the substance in the workplace has not been set. NIOSH in 2004 estimated that the number of persons occupationally exposed to cytotoxic drugs and other dangerous drugs in the USA exceeded 5 million.The main effects of methotrexate after intra-gastric, intramuscular or intravenous admin-istration include myelosuppression, hepatotox-icity and impaired fertility. In terms of exposure by inhalation, methotrexate can irritate the eyes and mucous membranes of the nose. This sub-stance is classified as irritating to the skin and eyes, category 2. Contact with the skin was found to be the most important risk factor for medical personnel exposed to cytotoxic drugs. The most frequently reported skin symptoms were associated with removal of methotrexate powder or solutions and in contact with the excrement of patients undergoing chemothera-py.Methotrexate induced genetic damage of deox-yribonucleic acid (DNA) in micronucleus, com-et and hprt gene mutation tests among workers employed in a plant manufacturing methotrex-ate. Chromosomal damage was found in the bone marrow of patients treated with metho-trexate. Animal studies confirmed methotrex-ate-induced genotoxicity.On the basis of available data, the International Agency Research on Cancer (IARC) concluded that there was no evidence of a carcinogenic effect of methotrexate in humans and animals (group 3). In a group of patients treated with methotrexate, there was no conclusive evidence of an increased risk of cancer. Methotrexate was not carcinogenic in chronic animal studies after intragastric, intraperitoneal or intravenous ad-ministration.It is proposed to determine the MAC values for the inhalable fraction of methotrexate at the level of 0.001 mg/m3. Determination of the limit value in the working environment for metho-trexate imposes on employers an obligation to monitor the concentration of this chemothera-peutic agent in the working environment. It will also make it possible to assess actual exposure of medical per-sonnel to this substance. The authors found basis for determining short-term ( STEL ) and permissible concentrations in biological materi-al (DSB) of methotrexate. It is also proposed to use the skin label in the list of occupational exposure limit because absorption through the skin may be as important as inhalation. Using the letters Ft – toxic to the fetus – is also pro-posed.

Authors and Affiliations

Małgorzat Kupczewska-Dobecka

Keywords

metotreksat cytostatyki narażenie zawodowe Methotrexate antineoplastics drugs occupational exposure

A review of the effects of exposure to a time-varying electromagnetic field and the metrological properties of measurement devices that have a significant influence when evaluating exposure in the work environment

Any use of electric devices and installations is inextricably linked to the intentional or uninten-tional emission of electromagnetic energy. Consequently, the electromagnetic field is commonly present in the environment...

EP ID EP81575
DOI -
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