Here we consider other anthropogenic organic chemicals and their by-products. Solvents include many types of liquid hydrocarbons, which are used as carriers for other materials, such as pigments in paints, or for rinsing oil and grease from manufactured items. Some, such as benzene, may also be components of fuel or raw materials for synthesis of other compounds. Some of the larger molecules we consider include the polynuclear aromatic hydrocarbons (PAHs), phthalate esters, and surfactants. Chlorinated organics are considered separately in the next section.
Many hydrocarbons are biotransformed by cytochrome P450 enzymes. Thus, they can interact with other toxins either positively by increasing cytochrome activity (as benzene does) or negatively by competing for the enzyme (as toluene does with benzene).
The solvents are hydrocarbons up to five or six carbons in size. They have appreciable vapor pressures, which may result in significant inhalation exposure. Solvents are also absorbed significantly through the skin in occupational settings. The larger compounds are more likely to be adsorbed to particles. Exposure can result from inhalation or ingestion of the particles. Some of them enter the food chain, where they can be bioaccumu-lated and ingested.
The major toxic effects common to these compounds are CNS depression, including narcosis, and irritation. These are of special concern with acute exposure to the solvents. However, these types of compounds can cause other effects, ranging from liver or kidney damage to carcinogenesis. CNS depression is essentially the action of a general anaesthetic. The potency of organics to produce CNS depression increases with the chain length of the compound. Halogenation, addition of an alcohol group, or unsaturation (removal of hydrogen to form a double carbon-carbon bond) increase potency as well.
One mechanism of irritation by hydrocarbons and surfactants is by the extraction of fats from the skin, lungs, eyes, or other cell membranes contacted. Addition of functional groups to an organic molecule tends to increase irritant properties. Amines and acidic groups make the compound corrosive, and alcohol, aldehyde, and ketone groups can precipitate and denature proteins associated with the membranes.
The aliphatic (saturated) hydrocarbons have relatively less toxicity than others do in this group. Ingestion of more than 1 mL/kg can produce systemic effects. For lower amounts, aspiration to the lungs is the principal concern. Chronic exposure, such as to hexane or heptane, produces neuropathy, probably due to metabolism to alcoholic and ketone forms. Olefinic (unsaturated) forms are stronger CNS depressants. Interestingly, the presence of double bonds eliminates the neurotoxicity of hexane and heptane. The cyclic hydrocarbons, such as cyclohexane, are similar to the open-chain forms, except that they are higher in irritancy, and do not seem to produce chronic effects.
Alcohols, including glycols, are much stronger CNS depressants than aliphatics are and slightly more irritating. As carbon chain length increases, irritation decreases but lipophi-licity increases, as does systemic toxicity. Methanol is less inebriating than ethanol but has the unusual property of destroying the optic nerve. Fifteen milliliters can cause blindness. As with ethanol, it is metabolized by a zero-order rate mechanism, but at one-seventh the rate. Ethanol acts as an irritant by dehydrating protoplasm. An initial stimulant effect is caused by depression of control mechanisms in the brain. Pain sensitivity is greatly reduced. Cutaneous (skin) blood vessels become dilated. The resulting increased heat loss can be dangerous in cold weather. It increases gastric secretion, which can aggravate stomach ulcers. It causes fat accumulation and cirrhosis in the liver. The latter can be fatal itself or can cause progression to cancer. Ethanol increases urine flow through a mechanism involving pituitary and adrenal hormones. The resulting water loss, along with the acetaldehyde by-product, may be a cause of the headache in a hangover. On the other hand, there is evidence that consumption of small amounts of alcoholic beverages with meals may have some benefits for the cardiovascular system.
Isopropyl alcohol is less toxic than n-propanol, but both these and butanol are more toxic than ethanol. Allyl alcohol is highly irritating. It can be absorbed through the skin, resulting in deep pain and possible burns of the eye. Glycols are compounds that have two hydroxyls on adjacent carbons. They are less toxic than the monohydroxy alcohols. Ethylene glycol can be fatal to humans with a single dose of 100 mL. It is biotrans-formed to oxalic acid, which blocks kidney function. Ethanol can inhibit this transformation, making it an antidote.
Aldehydes tend to be more irritating than they are CNS depressants. One unique toxicity of the aldehydes, especially formaldehyde, is sensitization. That is, it can increase a person's response to other chemicals. Formaldehyde is a common industrial chemical used in plastics and resins. The LD50 in humans for formalin (37 to 50% formaldehyde solution) is about 45 g, although deaths have been reported at as low as 30 g. Ingestion can produce headaches, GI tract corrosion, pulmonary edema, fatty liver, kidney necrosis, unconsciousness, and vascular collapse. Formaldehyde has been associated with muta-genicity and carcinogenicity in laboratory tests, but a steep dose-response relationship, the lack of epidemiological evidence for carcinogenicity in humans, plus the following facts, suggest the presence of a carcinogenicity threshold. Formaldehyde is a metabolic by-product, normally present at several ppm in tissues. Thus, it appears that carcinogeni-city is associated with exposures high enough to cause irritation and tissue injury. Acet-aldehyde is less irritating and toxic. Acrolein is an unsaturated propionaldehyde. The double bond greatly increases its reactivity as well as its irritant and toxic effect.
Ketones produce fewer occupational health problems, possibly because their irritant properties serve as a warning before other effects occur. Acetone causes skin irritation only after repeated lengthy contact. Eye irritation occurs with unacclimated persons at air concentrations of 500 ppmv, and repeated exposure can produce tolerance up to 2500 ppmv. Carboxylic acids are mostly irritants. Acidity, and irritation, decreases with chain length and increases with halogenation. Esters are stronger anesthetics than alcohols. The lower-carbon esters are stronger irritants than alcohols and can cause lacrima-tion (eye tearing). Phosphate esters are used as plasticizers and can cause CNS damage. Ethers are effective anesthetics and slightly irritating.
Amines have many uses, including as disinfectants in consumer products. They include some of the most toxic common industrial chemicals. Most simple amines have pKa values between 10.5 and 11.0, making them ionized at physiological pH and corrosive to tissues.
primary secondary tertiary amine amine amine
An important property of amines is that they are easily absorbed by all routes of exposure, including the skin. Thus, the dermal toxicity is often similar to the ingested toxicity (Table 21.7). Systemic effects include pulmonary edema and hemorrhage, liver and
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