PRINCIPLES OF TOXICOLOGY - Biology East Borneo

16.8 TOXIC PROPERTIES OF REPRESENTATIVE ALDEHYDES 387TABLE 16.5 Dose–Response Relationship for Formaldehyde in HumansHealth Effects ReportedFormaldehyde Air Concentration(ppm)None 0–0.5Odor detection 0.05–1.50Eye sensation and irritation 0.05–2.0Upper airway irritation 0.10–25Lower airway/pulmonary effects 5–30Pulmonary inflammation/edema 50–100Death >100the incidence is 5 percent or less. The primary irritant effects of formaldehyde are considered the mostsignificant problem.The fatal oral dose of formaldehyde is estimated to be 60–90 mL of formalin (37 percent).Depending on the dose, ingestion may cause headaches, corrosion of the gastrointestinal tract,pulmonary edema, fatty degeneration of the liver, renal tubular necrosis, unconsciousness, andvascular collapse.Formaldehyde has been tested in a variety of animal species and found not to cause reproductivetoxicities or teratogenicity. However, concerns have been raised with the recent findings of itsmutagenic activity in certain test systems and with its corresponding local carcinogenicity in rodents.While the exact mechanism of its mutagenic actions remains to be resolved, a recurrent finding inseveral test systems was that formaldehyde produces crosslinks within DNA, which generally arerecognized and repaired by the DNA repair enzyme system. The rodent carcinogenicity tests reveal asteep dose–response relationship, which suggests that a threshold may exist for this toxicity. Thefollowing points are consistent with this suggestion:• Formaldehyde is a common metabolite of normal cellular processes and serves as a cofactorin the synthesis of several essential biochemical substances. Tissue concentrations offormaldehyde may reach several ppm in normal physiological circumstances.• The mechanism for formaldehyde carcinogenicity appears to be a recurrent tissue injury andresultant hyperplasia caused by the high, irritating, and necrotizing exposures in the testsystems.• Epidemiological studies to date have not linked formaldehyde exposure to human cancer,nor have they indicated that persons chronically exposed to formaldehyde are at increasedrisk.Acetaldehyde (see Figure 16.11) is the next larger molecular weight aldehyde beyond formaldehydein the series and is also a common industrial chemical. Acetaldehyde is a normal metabolite ofmammalian ethanol metabolism and has been implicated by some authors as the “hangover” associatedwith expressive ethanol consumption. It is less reactive than formaldehyde and, therefore, is generallyless irritating and toxic than formaldehyde. It has not been found to be carcinogenic in animal tests,Figure 16.11 Acetaldehyde.