This chapter highlights common toxicologic problems in the workplace. Occupationally related disease is encountered commonly in the outpatient setting. Estimates of the proportion of occupationally related medical problems in primary care practices range up to 15-20%, although this includes many patients with musculoskeletal complaints. However, approximately 5% of all symptomatic poison control center consultations are occupational in nature, suggesting a large number of work-related chemical exposures do occur.

1. General considerations
   1. Occupational illness is rarely pathognomonic. The connection between illness and workplace factors is typically obscure unless a specific effort is made to link exposure to disease.
      1. Massive or catastrophic events leading to the acute onset of symptoms, such as release of an irritant gas, are relatively uncommon but easily recognized.
      2. For most workplace exposures, symptom onset is more often insidious, following a subacute or chronic pattern, as in heavy metal (eg, lead) poisoning.
      3. Long latency, often years between exposure and disease, makes linking cause and effect even more difficult—for example, in chronic lung disease or occupationally related cancer.
   2. Occupational evaluation frequently includes legal and administrative components.
      1. Occupational illness, even if suspected but not established, may be a reportable illness in certain states (eg, in California through its Doctor's First Report system).
      2. Establishing quantifiable documentation of adverse effects at the time of exposure may be critical to future attribution of impairment (eg, spirometric evaluation soon after an irritant inhalant exposure).
      3. Although workers' compensation is in theory a straightforward “no-fault” insurance system, in practice it often is arcane and adversarial. It is important to remember that the person being treated is the patient, not the employer or a referring attorney.
2. Components of the occupational exposure history
   1. Job and job process
      1. Ask specifics about the job. Do not rely solely on descriptions limited to a general occupation or trade, such as “machinist,” “painter,” “electronics worker,” or “farmer.”
      2. Describe the industrial process and equipment used on the job. If power equipment is used, ascertain how it is powered to assess carbon monoxide exposure risk.
      3. Determine whether the work process uses a closed system (eg, a sealed reaction vat) or an open system. Ascertain what other processes or workstations are nearby. Work under a laboratory hood may be an effectively “closed” system, but not if the window is raised too far or if the airflow is not appropriately calibrated.
      4. Find out who does maintenance and how often it is done.
   2. Level of exposure
      1. Ask whether dust, fumes, or mist can be seen in the air at the work site (even an outdoor work environment). If so, question whether coworkers or nearby objects can be seen clearly (very high levels actually obscure sight). A history of dust-laden sputum or nasal discharge at the end of the work shift is also a marker of heavy exposure.
      2. Ask whether work surfaces are dusty or damp and whether the paint at the work site is peeling or discolored (eg, from a corrosive atmosphere).
      3. Determine whether strong smells or tastes are present and, if so, whether they diminish over time, suggesting olfactory fatigue.
      4. Find out whether there is any special ventilation system and where the fresh air intake is located (toxicants can be entrained and recirculated by a poorly placed air intake system).
      5. Establish whether the person has direct skin contact with the materials worked with, especially solvents or other liquid chemicals.
      6. Work in a confined space can be especially hazardous. Examples of such spaces include ship holds, storage tanks, and underground vaults.
   3. Personal protective gear. Respiratory system and skin protection may be essential for certain workplace exposures. Just as important as the availability of equipment are proper selection, fit assessment, and use.
      1. Respiratory protection. A disposable paper-type mask is inadequate for most exposures. A screw-in cartridge-type mask whose cartridges are rarely changed is also unlikely to be effective. For an air-supplied respirator with an air supply hose, ascertain the location of the air intake.
      2. Skin protection. Gloves and other skin protection should be impervious to the chemical(s) used.
   4. Temporal aspects of exposure
      1. The most important question is whether there have been any changes in work processes, products used, or job duties that could be temporally associated with the onset of symptoms.
      2. Patterns of recurring symptoms linked to the work schedule can be important—for example, if symptoms are different on the first day of the workweek, at the end of the first shift of the week, at the end of the workweek, or on days off or vacation days.
   5. Other aspects of exposure
      1. It is critical to assess whether anyone else from the workplace is also symptomatic and, if so, to identify that person's precise job duties.
      2. Eating or drinking in work areas can result in exposure through ingestion; smoking on the job can lead to inhalation of native materials or toxic pyrolysis products of contaminated cigarettes.
      3. Determine whether a uniform is provided and who launders it. For example, family lead poisoning can occur through work clothes brought home for laundering. After certain types of contamination (eg, with pesticides), a uniform should be destroyed, not laundered and reused.
      4. Find out how large the work site is, because small operations are often the most poorly maintained. An active work safety and health committee suggests that better general protection is in place.
   6. Common toxic materials of frequent concern that are appropriate to address in the occupational exposure history
      1. Two-part glues, paints, or coatings that must be mixed just before use, or one-part variants of these, such as urethanes and epoxides. These reactive polymers are often irritants or sensitizers.
      2. Solvents or degreasers, especially if the level of exposure by inhalation or through skin contact is high enough to cause dizziness, nausea, headache, or a sense of intoxication.
      3. Respirable dusts, including friable insulation or heat-resistant materials, and sand or quartz dust, especially from grinding, drilling, or blasting.
      4. Combustion products or fumes from fires, flame cutting, welding, and other high-temperature processes or engine exhaust.
   7. Identifying the specific chemical exposures involved may be difficult because the worker may not know or may not have been precisely informed about them. Even the manufacturer may be uncertain because components of the chemical mixture were obtained elsewhere or because exposure is due to undetermined process byproducts. Finally, the exposure may have occurred long before. Aids to exposure identification include the following:
      1. Product labels. Obtain product labels as a first step. However, the label alone is unlikely to provide sufficiently detailed information.
      2. Safety data sheets. Contact the manufacturer directly for a safety data sheet (SDS). These must be provided upon a physician's request in cases of suspected illness. Do not take no for an answer. You may need to supplement the SDS information through direct discussion with a technical person working for the supplier because key information may not be provided (eg, an ingredient may not be specified because it is a small percentage of the product or treated as a “trade secret”).
      3. Computerized databases. Consult computerized databases, such as Poisindex, HSDB (Hazardous Substances Data Bank), Toxnet, TOMES (Toxicology Occupational Medicines and Environmental Sciences), NIOSHTIC (NIOSH Technical Information Center), and others, for further information. Regional poison control centers (1-800-222-1222) can be extremely useful.
      4. Department of Transportation identification placards. In cases of transportation release, DOT identification placards may be available (Figure IV-3).
      5. Industrial exposure data. Rarely, detailed industrial hygiene data may be available to delineate specific exposures and exposure levels in cases of ongoing, chronic exposure.
      6. Existing process exposure data. Often, likely exposure can be inferred on the basis of known specific exposures strongly associated with certain work activities. Selected types of exposure are listed in Table IV-1.
3. Organ-specific occupational toxidromes. A list of the 10 leading work-related diseases and injuries was developed a number of years ago by the National Institute for Occupational Safety and Health (NIOSH). This list, organized generally by organ system, is included in Table IV-2, along with additional disorders that were not on the original NIOSH list.
   1. Occupational lung diseases
      1. In acute pulmonary injury from inhaled irritants, exposure is typically brief and intense; initial symptom onset occurs from within minutes to between 24 and 48 hours after exposure. The responses to irritant exposure, in order of increasing severity, are mucous membrane irritation, burning eyes and runny nose, tracheobronchitis, hoarseness, cough, laryngospasm, bronchospasm, and pulmonary edema progressing to acute respiratory distress syndrome (ARDS). Gases with lower water solubility (nitrogen dioxide, ozone, and phosgene) may produce little upper airway mucous membrane irritation. Injury from water-repellent fluoropolymer aerosol inhalation presents similarly to injury from the low-solubility gases. Any irritant (high or low solubility) can cause pulmonary edema and ARDS after sufficient exposure.
      2. Heavy metal pneumonitis is clinically similar to irritant inhalation injury. As with low-solubility gases, upper airway mucous membrane irritation is minimal; thus, the exposure may have poor warning properties. Offending agents include cadmium, mercury, and, in limited industrial settings, nickel carbonyl. Other toxic metal carbonyls (eg, iron pentacarbonyl) are rarely encountered.
      3. Febrile inhalational syndromes are acute, self-limited, flulike syndromes that include the following: metal fume fever (caused by galvanized metal fumes); polymer fume fever after intermediate temperature thermal breakdown of certain fluoropolymers (a different syndrome from acute irritant injury from high temperature fluoropolymer breakdown or from water-repellent fluoropolymer injury); and organic dust toxic syndrome (ODTS; after heavy exposure to high levels of organic dust, such as occurs in shoveling wood chip mulch). In none of these syndromes is lung injury marked. The presence of hypoxemia or lung infiltrates suggests an alternative diagnosis (see Items 1 and 2 above).
      4. Work-related asthma is a common occupational problem. Classic occupational asthma typically occurs after sensitization to either high-molecular-weight chemicals (eg, inhaled foreign proteins) or small chemicals (the most common of which are urethane isocyanates such as toluene diisocyanate [TDI]). After acute, high-level irritant inhalations of, for example, chlorine, a chronic irritant-induced asthma may persist (sometimes called reactive airways dysfunction syndrome [RADS]).
      5. Chronic fibrotic occupational lung diseases include asbestosis, silicosis, coal workers' pneumoconiosis, and a few other, less common fibrotic lung diseases associated with occupational exposures to substances such as beryllium, hard metal (cobalt-tungsten carbide), indium tin oxide (flat screen display manufacture) and short-length synthetic textile fibers (flock worker's lung). These conditions typically occur after years of exposure and have a long latency, although patients may present for evaluation after an acute exposure. Referral for follow-up surveillance is appropriate.
      6. Other occupational lung disorders. Hypersensitivity pneumonitis (also called allergic alveolitis) includes a group of diseases most commonly caused by chronic exposure to organic materials, especially thermophilic bacteria or to bird-derived antigens. The most common of these is farmer's lung. Certain chemicals can also cause this disease (eg, isocyanates). Although the process is chronic, acute illness can occur in a sensitized host after heavy exposure to the offending agent. Other work-related lung syndromes include constrictive bronchiolitis obliterans from the flavorant diacetyl (eg, microwave popcorn worker's lung), proliferative bronchiolitis from nitrogen dioxide (eg, silo filler's lung), and bronchiectasis following severe irritant inhalation injury (eg, from concentrated ammonia).
   2. Musculoskeletal conditions, including acute mechanical trauma, comprise the most common group of occupational medicine problems but rarely have direct toxicologic implications.
      1. Raynaud syndrome may be associated rarely with chemical exposure (eg, vinyl chloride monomer).
      2. High-pressure injection injuries (eg, from paint spray guns) are important not because of systemic toxicity resulting from absorption of an injected substance (eg, paint thinner) but because of extensive irritant-related tissue necrosis. Emergency surgical evaluation is mandatory.
      3. Rhabdomyolysis may occur as a consequence of selected toxicants.
   3. Occupational cancer is a major public concern and often leads to referral for toxicologic evaluation. A variety of cancers have been associated with workplace exposure, some more strongly than others. Attributing a chemical cause to an individual case of cancer can be challenging. The process of attribution, however, tends to be far removed from the acute care setting, and clinical oncology management is not affected directly by such etiologic considerations.
   4. Cardiovascular disease
      1. Atherosclerotic cardiovascular disease is associated with carbon disulfide. This chemical solvent is used in rayon manufacturing and in specialty applications and research laboratories. It is also a principal metabolite of disulfiram.
      2. Carbon monoxide (CO) at high levels can cause myocardial infarction in otherwise healthy individuals, and at lower levels it can aggravate ischemia in the face of established cardiovascular disease. Many jurisdictions automatically grant workers' compensation to firefighters or police officers with coronary artery disease, regarding it as a “stress-related” occupational disease in addition to possible CO effects in the former group.
      3. Nitrate withdrawal-induced coronary artery spasm has been reported among workers heavily exposed to nitrates during munitions manufacturing.
      4. Hydrocarbon solvents, especially chlorinated hydrocarbons, and chlorofluorocarbon propellants all enhance the sensitivity of the myocardium to catecholamine-induced dysrhythmias.
   5. Adverse reproductive outcomes have been associated with or implicated in occupational exposures, including heavy metals (eg, lead and organic mercury), hospital chemical exposures (including anesthetic and sterilizing gases), and dibromochloropropane (a soil fumigant now banned in the United States).
   6. Occupational neurotoxins
      1. Acute central nervous system (CNS) toxicity can occur with many pesticides (including both cholinesterase-inhibiting and chlorinated hydrocarbons). The CNS is also the target of methyl bromide (a structural fumigant Methyl Bromide) as well as the related toxin methyl iodide. Cytotoxic and anoxic asphyxiant gases (eg, carbon monoxide, cyanide, and hydrogen sulfide) all cause acute CNS injury, as can bulk asphyxiants (eg, carbon dioxide). Hydrocarbon solvents are typically CNS depressants at high exposure levels.
      2. Chronic CNS toxicity is the hallmark of heavy metals. These include inorganic forms (arsenic, lead, and mercury) and organic forms (tetraethyl lead, methyl mercury, and dimethylmercury). Chronic manganese exposure can cause psychosis and parkinsonism. Other causes of parkinsonism include carbon disulfide and postanoxic injury (especially from carbon monoxide).
      3. Established causes of peripheral neuropathy include lead, arsenic, tributyl tin, carbon disulfide, n-hexane (magnified in combination with methyl ethyl ketone), 1-bromopropane, and certain organophosphates.
   7. Occupational ototoxicity is common but is usually noise-induced rather than chemically related. Pre-existing noise-induced hearing loss may magnify the impact of common ototoxic drugs and some chemicals.
   8. Occupational skin disorders
      1. Allergic and irritant and photocontact dermatitis, contact urticaria, and acute caustic chemical or acid injuries are the most common toxin-related skin problems. Systemic toxicity may occur but is not a common complicating factor.
      2. Hydrofluoric acid burns present a specific set of management problems. Relevant occupations include not only those in the microelectronics industry but also maintenance or repair jobs in which hydrofluoric acid-containing rust removers are used.
   9. Work-related psychological disorders include a heterogeneous mix of diagnoses. Among these, posttraumatic stress disorder (PTSD) and “mass psychogenic illness” can be extremely relevant to medical toxicology because the patients may believe that their symptoms have a chemical etiology. After reasonable toxicologic causes have been excluded, psychological diagnoses should be considered when nonspecific symptoms or multiple somatic complaints cannot be linked to abnormal signs or physiologic effects.
   10. Occupational chemical hepatotoxins (see also Table I-28)
       1. Causes of acute chemical hepatitis include exposure to industrial solvents such as halogenated hydrocarbons (methylene chloride, trichloroethylene, trichloroethane, and carbon tetrachloride, the latter only rarely encountered in modern industry), and nonhalogenated chemicals such as dimethylformamide, dinitropropane, and dimethylacetamide. The jet and rocket fuel components hydrazine and monomethylhydrazine are also potent nonhalogenated hepatotoxins.
       2. Other hepatic responses that can be occupationally related include steatosis, cholestatic injury, hepatoportal sclerosis, and hepatic porphyria. The acute care provider should always consider a toxic chemical etiology in the differential diagnosis of liver disease.
   11. Renal diseases
       1. Acute tubular necrosis can follow high-level exposure to a number of toxins (the more common exposure scenario is a suicide attempt by ingestion rather than workplace inhalation).
       2. Renal tubular acidosis can complicate solvent inhalation abuse (eg, toluene).
       3. Interstitial nephritis is associated with chronic exposure to heavy metals, whereas chronic hydrocarbon exposure has been associated epidemiologically with glomerular nephritis, particularly Goodpasture disease.
   12. Hematologic toxicity
       1. Industrial oxidants are an important potential cause of chemically induced methemoglobinemia, especially in the dyestuff and munitions industries.
       2. Bone marrow is an important target organ for certain chemicals, such as benzene and methyl cellosolve. Both can cause pancytopenia. Benzene exposure also causes leukemia in humans. Lead causes anemia through interference with hemoglobin synthesis.
       3. Arsine gas is a potent cause of massive hemolysis. It is of industrial importance in microelectronics manufacturing.
   13. Nonchemical physical exposures in the workplace are important because they can cause systemic effects that mimic chemical toxidromes. The most important example is heat stress, which is a major occupational health issue. Other relevant nonchemical, work-related types of physical exposure include ionizing radiation, nonionizing radiation (eg, ultraviolet, infrared, and microwave exposure), and increased barometric pressure (eg, among caisson workers). Except for extremes of exposure, the adverse effects of these physical factors generally are associated with chronic conditions.
   14. Systemic poisons fit poorly into organ system categories but are clearly of major importance in occupational toxicology. Prime examples are the cytotoxic asphyxiants hydrogen cyanide (especially in metal plating and metal refining), hydrogen sulfide (important as a natural byproduct of organic material breakdown), and carbon monoxide (principally encountered as a combustion byproduct but also a metabolite of the solvent methylene chloride). Arsenic is a multiple-organ toxin with a myriad of effects. It has been used widely in agriculture and is an important metal smelting byproduct. A systemic disulfiram reaction can occur as a drug interaction with concomitant exposure to certain industrial chemicals. Toxicity from dinitrophenol, an industrial chemical that uncouples oxidative phosphorylation, is also best categorized as a systemic effect. Pentachlorophenol, a severely restricted wood preservative, acts similarly. Phosphine is a systemically toxic fumigant.
4. Laboratory testing
   1. Testing for specific occupational toxins has a limited but important role. Selected tests are listed in the descriptions of specific substances in Section II of this book. For significant irritant inhalation exposures, in addition to assessing oxygenation and chest radiographic status, early spirometric assessment is often important.
   2. General laboratory testing for chronic exposure assessment should be driven by the potential organ toxicity delineated previously. Standard generic recommendations (eg, in NIOSH criteria documents) often include a complete blood cell count, electrolytes, tests of renal and liver function, and periodic chest radiographic and pulmonary function studies.
5. Treatment
   1. Elimination or reduction of further exposure is a key treatment intervention in occupational toxicology. This includes prevention of exposure to coworkers. The Occupational Safety and Health Administration (OSHA) should be notified immediately about a potentially life-threatening workplace exposure situation: call the 24-hour hotline (1-800-321-6742). Less urgent reports can also be made online: https://www.osha.gov/report.html. Workplace modification and control, especially the substitution of less hazardous materials, should always be the first line of defense. Worker-required personal protective equipment is, in general, less preferred as a preventive measure.
   2. The medical treatment of occupational toxic illness should follow the general principles outlined earlier in this section and in Sections I and II of this book. In particular, the use of specific antidotes should be undertaken in consultation with a regional poison control center (1-800-222-1222) or other specialists. This is particularly true before chelation therapy is initiated for heavy metal poisoning.