PRINCIPLES OF TOXICOLOGY - Biology East Borneo

382 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTSWhile PAHs can be acutely toxic, this characteristic generally is relevant only at doses sufficientlygreat that they are not of interest in an industrial or environmental setting. At high, acute doses, PAHsare toxic to many tissues and degenerative changes may ultimately be observed in the kidney and liver,but the thymus and spleen are particularly sensitive to acute effects. For example, the noncarcinogenPAH acenaphthene, given in doses as high as 2000 mg/kg, produces only minor changes in the liveror kidney and is relatively nontoxic when compared to the hematoxicity produced by 100 mg/kg ofdimethylbenzanthracene, a much more potent PAH.Several of the PAHs with four, five, or more rings (e.g., benzo-a-pyrene, benzo-a-anthracene,benzo-b,k-fluoranthene) have been classified as possible carcinogens by a number of environmentalregulatory agencies. Occupational guidelines have been established for a chemical category known as“coal tar pitch volatiles,” which includes some PAHs.16.6 TOXIC PROPERTIES OF REPRESENTATIVE ALCOHOLSAlcohol Compounds: R–OHAs a general observation, alcohols are more powerful CNS depressants than their aliphatic analogs. Insequence of decreasing depressant potential, tertiary alcohols with multiple substituent OH groups are morepotent than secondary alcohols, which, in turn, are more potent than primary alcohols. The alcohols alsoexhibit irritant potential and generally are stronger irritants than similar organic structures that lack functionalgroups (e.g., alkanes) but are much less irritating than the corresponding amines, aldehydes, or ketones. Theirritant properties of the alcohol class decrease with increasing molecular size. Conversely, the potential foroverall systemic toxicity increases with greater molecular weight, principally because the water solubilityis diminished and the lipophilicity is increased. Alcohols and glycols (dialcohols) rarely represent serioushazards in the workplace, because their vapor concentrations are usually less than the required irritant levels,which, in turn, prevents significant CNS effects as well.Methanol (see Figure 16.5), also known as methyl alcohol or wood alcohol, is the simplest structuralmember of the alcohols and is widely employed as an industrial solvent and raw material formanufacturing processes. It also is used as one of several possible adulterants to “denature” ethylalcohol, which then is used for cleaning, paint removal, and other applications. The denaturing processin theory prevents its ingestion.Methanol is of toxicological interest and industrial significance because of its unique toxicity tothe eye, and it has received considerable attention from the medical community over the years due tomisuse, as well as accidental or intentional human consumption. It has been estimated that methanolingestion may have been responsible for 5–10 percent of all blindness in the U.S. military forces duringWorld War II. Methanol intoxication typically exhibits one or more of the following features:• CNS depression, similar to or greater than that produced by ethyl alcohol (ethanol)• Metabolic acidosis, caused by degradation of methanol to formic acid and other organic acids• Ototoxicity, expressed as specific toxicity to retinal cells caused by formaldehyde, anoxidation product of methanolFigure 16.5 Met hanol.