PRINCIPLES OF TOXICOLOGY - Biology East Borneo

386 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTSFigure 16.9 Aldehyde compounds.who have been exposed to formaldehyde merely by wearing “permanent press” fabrics containingmelamine-formaldehyde resins. Because their irritant effects limit inhalation exposure, theindustrial use of aldehydes is relatively free of problems associated with other systemic or organtoxicities of a serious nature. However, at sufficient concentration, damage to the respiratory tractis possible.Unsubstituted aldehydes (e.g., acrolein and ketene) are particularly toxic. The double bond in closeassociation with the aldehyde functional group renders these compounds more reactive, and thereforemore toxic, than the unsubstituted analogs. For example, ketene and acrolein are on the order of 100times more potent when measuring acute lethality by inhalation than either acetaldehyde or proprionaldehyde.Reflecting this increase in potency is the fact that potential damage to the respiratory systemis also more severe, resembling the deep lung damage of phosgene. Once absorbed, the systemictoxicity of the unsaturated aldehydes is also more severe than that of the saturated members of theclass.Mutagenicity of some aldehydes (e.g., acrolein, formaldehyde, and acetaldehyde) suggests carcinogenicpotential of these compounds. Some of these substances are regulated as possible carcinogensby various occupational and environmental agencies.Formaldehyde (see Figure 16.10) is the simplest structural member of the aldehyde family. Italso is the most important aldehyde in both commerce from an economic perspective, and theenvironment from a regulatory perspective, and over 7 billion pounds are produced in the UnitedStates annually. Because of its reactivity and instability in the pure form, it is generally marketedin aqueous solution ranging from 37 to 50 percent formaldehyde (known as formalin). Thisproduct generally is diluted 1:10 for laboratory use, resulting in a typical usable concentration ofapproximately 4 percent. Formaldehyde also is readily available in two other forms, trioxymethylene(the cyclic trimer), and a low-molecular-weight homopolymer, paraformaldehyde.The latter is used primarily in the plastic and resins industries, in the synthesis of chemicalintermediates and, less frequently, in sealants, cosmetics, disinfectants, foot-care creams, mouthwashes,embalming fluids, corrosion inhibitors, film hardeners, wood preservatives, and biocides.Formaldehyde is a fairly strong dermal irritant, and its local actions dominate the adverse effectsthat are observed following excessive exposure, in comparison to the systemic effects that mightotherwise occur. Table 16.5 describes the continuous nature of the dose-response relationship forirritant effects from formaldehyde exposures. It also illustrates the range of effective concentrationsreported for the human population. Formaldehyde can produce dermal sensitization reactions inapproximately 4 percent of the population, making it the tenth most common cause of dermatitis.With repeated application of high concentration, irritating solutions of formaldehyde inducessensitization in about 8 percent of the male subjects tested, but with lower concentrations (