Scientific approach to derive occupational exposure limits for formaldehyde releasers

Formaldehyde is highly reactive, causing irritation and acute and chronic toxicity in target tissues (the eyes, respiratory tract, and skin) following inhalation and/or skin contact. Moreover, formaldehyde is a local carcinogen after inhalation exposure. It induces nasal squamous cell carcinoma in laboratory animals and nasopharyngeal carcinoma in humans, albeit less convincingly. While formaldehyde has been evaluated and classified by different organizations and committees in recent years, the question has arisen of how to deal with substances that release formaldehyde. These releasers decompose in aqueous media and are frequently used as biocides in water-miscible metalworking fluids, adhesives, paints, disinfectants, and cosmetics. In this context, the MAK Commission has developed a concept for differential evaluation regarding carcinogen classification and MAK value derivation. This approach is based on hydrolysis rates as a function of pH, temperature, and concentration under physiological conditions. Furthermore, vapor pressure is considered to determine whether the formaldehyde releaser will be present as a vapor or aerosol upon inhalation. This concept is demonstrated using four examples that lead to different carcinogen classifications and MAK value derivations. Additionally, the releasers were evaluated for percutaneous absorption and sensitization.