8 Toxic Exposures

HEALTHY HOMES

The concept of a “healthy home” as promoted by the U.S. Department of Housing and Urban Development (HUD) and other federal agencies involves not only aspects of the built environment (see Chapter 6), but also creating homes that are safe in terms of toxic hazards such as carbon monoxide and pesticides.¹ This concept is one in which human health care providers, public health professionals, and veterinarians can actively collaborate because it seems clear that what is good for the human beings in the household in terms of toxic hazard reduction is also good for animals living in the household.

In the early part of the twentieth century, miners in the United States and Great Britain brought caged canaries into mines to provide an early warning of the presence of deadly gases such as carbon monoxide and methane. Studies had shown that the canaries were more sensitive than other species to the effects of these gases,² and a canary becoming ill and falling from its perch was sufficiently recognizable to warn the miners of the hazard. In the same way, animals living in or near a household can serve as “sentinels” for human health hazards related to toxic exposures in the home and other environments. Much of what is known about the toxic properties of environmental chemicals is based on studies of laboratory animals such as rats and mice. However, pets, other domestic animals, and wildlife can provide both clinically important information to human health as well as useful “animal models” of cancer and other environmentally induced disease.³

At times it is the human being who first presents to medical care with a toxic syndrome that is relevant to animals in the household. Greater access to medical care and diagnostic services may result in diagnosis in the human case before related animal cases.

This chapter outlines acute poisoning and chronic toxic exposure situations for human beings and other animals and indicates certain scenarios in which a toxicant-related disease event in one species could be an indicator of risk for other species. This section provides an overview of acute and chronic toxic exposures in different species. Subsequent sections provide specific information on toxicity caused by carbon monoxide, lead, animal-related pesticides, envenomations, and harmful algae blooms (HABs).

Key Points for Clinicians and Public Health Professionals

Public Health Professionals

• Educate the public on principles for a safer, healthier home:

Eliminate tobacco smoking from the home.

Use safer substances for general cleaning (e.g., vinegar, lemon juice).

Store medications out of reach of children and pets.

Eliminate toxic substances from the home or store them out of reach of children and animals.

Use nontoxic plants in and around the home.

Use integrated pest management (IPM) techniques for rodent, weed, and insect control to reduce dependence on toxic substances. (See, for example, http://www.epa.gov/pesticides/factsheets/ipm.htm.) IPM is a commonsense and environmentally sensitive approach to pest management that uses current, comprehensive information on the life cycles of pests and their interaction with the environment.

Human Health Clinicians

• Consider toxic exposures in the differential diagnosis of both acute and chronic medical problems.

• If unusual health events are occurring in pets and/or other animals, consider whether this could be a sentinel event warning of human health risk from an environmental toxic hazard.

• An acute poisoning episode in a pet could be a warning of inappropriate access to hazardous substances and the need for steps to prevent exposures to children.

• Counsel smokers on the importance of smoking cessation to benefit their own health and the health of others in the household (including pets).

• Be aware of cultural and ritualistic use of toxic substances such as mercury, which may endanger household members and companion animals (see http://www.epa.gov/superfund/community/pdfs/merc_rep05.pdf).

• Judiciously prescribe medications and counsel patients to keep medications and other toxic hazards stored out of the reach of children and companion animals.

Veterinary Clinicians

• Consider toxic exposures in the differential diagnosis of both acute and chronic animal illness.

• If toxic exposures are identified in animal patients, consider whether human beings could also be at risk and contact public health authorities.

• An acute poisoning episode in a pet could be a warning of inappropriate access to hazardous substances and the need for steps to prevent exposures to children.

• If owners report toxic exposures diagnosed in human beings in the household, consider whether animals are also at risk.

• Judiciously prescribe medications and counsel owners to keep medications stored out of the reach of children and companion animals.

• Counsel owners not to use any medications in their animals unless prescribed by a veterinarian.

• Counsel owners about the least-toxic chemicals for pest control and the use of IPM techniques.

PRIMARY PREVENTION OF TOXIC EXPOSURE

Human health and veterinary health clinicians can recommend a number of preventive steps to their patients and clients, respectively, to reduce the risk of toxic exposures to human beings and other animals.

Pet Proofing and Child Proofing

Pets and children share the potential for accidentally ingesting toxic substances left around a house or yard. Keep toxic substances such as cleaning solutions, flea and tick preparations, other pesticides, and all medications out of reach of pets and children. Encourage smoking cessation to protect the health of the smoker and human beings and animals exposed to secondhand smoke (Figure 8-1).

Figure 8-1 Eliminate tobacco smoke in the house.

(From Centers for Disease Control and Prevention Public Health Image Library, Atlanta, Ga.)

Judiciously Prescribe Medications

Human and veterinary clinicians should weigh the relative value of prescribing medications by considering such issues as antibiotic resistance, drug interactions, entrance of pharmaceuticals into community drinking water, and assurance that drugs are taken only by the individuals for whom they are prescribed. Patient/owner education should be carefully reviewed such that judiciously prescribed medications should never be administered to other people, household pets, or other animals. In addition, over-the-counter medications should be administered only to a companion animal based on the veterinarian’s treatment plan for that animal.

Substitution: “Green” Chemistry

One way to reduce the risk of acute and chronic poisoning is to consider less-toxic substitutes for many household uses. In general, keeping the residence uncluttered, food sources appropriately stored, and surfaces clean and dry will eliminate much of the need for more-toxic substances. In addition, “green” or “sustainable” chemistry encourages the design and use of products that ultimately eliminate the need for hazardous substances.

The public should use caution with herbal remedies in the belief that these substances as substitutes for conventional pharmacology. Adverse events may occur and antidotes may not be available.

ANIMALS AS SENTINELS FOR HUMAN TOXIC EXPOSURE RISK

Six years before the detection of Minamata disease, an outbreak of severe methyl mercury poisoning among families living near Minamata Harbor in Japan, strange clinical signs were seen in local cats that ate diets high in fish from the bay. This “dancing cat disease” included twitching, spasms, abnormal movements, and convulsions. Only later was the association made between the neurological signs in the cats and the devastating signs of mercury poisoning in children and adults (who also ate mercury-contaminated fish from the bay) that included mental retardation, seizures, and other neurological damage.⁴

The inappropriate use of melamine as a filler substance in pet foods has been blamed for thousands of animal deaths from renal failure.⁵ Unfortunately, this scandal did not protect against the subsequent unscrupulous use of the “protein booster” in powdered baby formula in China, which led to illness and death in human infants the following year.⁶

A National Academy of Sciences panel has concluded that domestic animals and wildlife could serve as useful sentinels of human environmental health hazards because they may develop recognizable signs or biomarkers of toxicity in a timely way to provide a warning to human beings and to assist in human risk assessment.⁷ Animals may function as sentinels when there are differences between animals and human beings regarding exposure, susceptibility, or latency to a particular hazard. At times, an unusual cluster of disease in an animal population may suffice to draw attention to a particular hazard. For example, when horses (and dogs) in Times Beach, Missouri, began to die after their stable area was sprayed with oil to control dust, it was discovered that the oil was contaminated with dioxin.⁸ The Times Beach incident was the largest community-wide exposure to dioxin in the United States.

Routes of Exposure

Perhaps the most likely opportunity for animals to serve as sentinels of household toxic exposures is by their greater exposure risk. Dogs are well known for their propensity to ingest a wide variety of substances, including lead-containing dusts and household cleaning agents, and therefore may be the first in a household to manifest signs. Household pets also spend more time in the home environment and thus could have a higher exposure risk to a number of substances present in the home. For example, cats and dogs may have increased exposure to dust compared with human beings because they live close to the floor level and often lick their fur during grooming (especially cats). Dust in a household may contain accumulations of chemicals, including flame retardants, lead, mercury, phthalates, and perfluorochemicals (used in nonstick cookware) and can lead to significant toxic exposures in human beings and other animals in the house. A recent study of levels of chemicals in the blood and urine of dogs and cats found levels of flame retardants in cats more than 20 times the average level in human populations, levels of mercury more than five times as high, and levels of perfluorochemicals in dogs more than double that found in the general human population.⁹ These finding indicate that pets may have increased exposure to many toxicants found in household dust and fumes compared with human beings and therefore may be at risk of showing signs sooner or with greater severity.

Outdoors, dogs and cats may dig in the soil around a house or in adjacent neighborhoods, exposing themselves to lead, pesticides, arsenic, and other toxic chemicals that could be in soil. Some authorities have expressed concern that pets could then track such contaminated soil into a house on their paws and fur, potentially increasing the exposure risk for children and other inhabitants.¹⁰ Wildlife and livestock often live continuously in outdoor environments near human beings and may be exposed to toxicants in water, air, soil, and food sources, including vegetation, at much higher levels than human beings.

Metabolic Fate/Susceptibility

Physiological differences in metabolism in some animals may make them more sensitive than human beings to certain toxicants. Canaries were found to be more sensitive than human beings to the toxic effects of carbon monoxide and methane gas in coal mines, allowing them to provide early warning to miners if they began to act sick (Figure 8-2). Dogs lack the metabolizing enzyme rhodanese and therefore may have effects of cyanide poisoning at lower doses than human beings. Birds appear to be more sensitive than human beings to inhalation of fumes from burning polytetrafluoroethylene (PTFE; Teflon [DuPont, Wilmington, Del.]).¹¹

Figure 8-2 Canaries are popular caged birds that are revered for their beauty and singing qualities.

(From Tully TN Jr: Birds. In Mitchell MA, Tully TN Jr (eds): Manual of exotic pet practice, St Louis, 2008, Saunders Elsevier.)

Susceptibility to acute and chronic exposure to toxicants may vary within species according to breed, sex, age, neutering status, or other differences. For example, the risk of nasal cancer in dogs (which has been linked to indoor air pollution; see below) may be higher in long-nosed dogs because of anatomical differences that allow different degrees of contact between carcinogenic air pollutants such as polyaromatic hydrocarbons (PAHs) and the lining of their nasal passages compared with short-nosed dogs.¹² An increased risk of bladder cancer has been reported in obese female dogs; the reasons for this are not clear.¹²

An example of interspecies differences in susceptibility to toxic exposures can be seen in the list of human foods that are toxic to some companion animals (Table 8-1) and common human medications that may be highly toxic to pets at relatively low doses.

Table 8-1 Partial List of Foods Toxic to Companion Animals

Food (Ingredient)	Toxic Effect in Dogs	Toxic Effect in Cats
Alcoholic beverages (ethanol)	Ataxia, respiratory depression, cardiac abnormalities, death (acute toxicity with 5-8 mL/kg; oral LD₅₀ 5500 mg/kg in dogs)	Ataxia, respiratory depression, cardiac abnormalities, death (acute toxicity with 5-8 mL/kg)
Avocado (persin)	Vomiting, diarrhea	None known
Chocolate (theobromine)	Vomiting, diarrhea, tremors, seizures, death (250-500 mg/kg LD₅₀ in dogs)	Vomiting, diarrhea, tremors, seizures, death (200 mg/kg LD₅₀ in cats)
Coffee (all forms) (caffeine)	Vomiting, diarrhea, tremors, seizures, death (LD₅₀ 140-150 mg/kg in dogs)	Vomiting, diarrhea, tremors, seizures, death (LD₅₀ 100-150 mg/kg in cats)
Fatty foods	Steatorrhea, diarrhea, obesity, pancreatitis	Steatorrhea, diarrhea, obesity
Macadamia nuts	Vomiting, depression, ataxia (2.2 g/kg)¹³	None known
Moldy foods (tremorgenic mycotoxins)	Muscle tremors, seizures	Muscle tremors, seizures
Onions, onion powder, garlic, leeks, chives (propyl disulfide)¹³	Hemolysis (11 g raw onions/kg)	Hemolysis (28 g raw onion/kg)
Raisins and grapes	Acute renal failure (no apparent dose response)	None known
Yeast dough (ethanol)	Abdominal distention, ethanol toxicosis	Abdominal distention, ethanol toxicosis

LD₅₀, Median lethal dose.

Latency

Another way in which animals may be a sentinel for human illness is if they develop signs in a shorter period of time (latency). This may be more important for chronic rather than acute toxic exposures. Most companion animals have a shorter average lifespan than human beings. Therefore chronic disease effects from environmental exposures tend to have a shorter latency. An example is the finding of mesothelioma in dogs whose owners had occupational or hobby exposure to asbestos (which resulted in secondary exposure of the household dog and other human beings in the household) (Color Plate 8-1). The average age of the dogs at time of diagnosis was 8 years (48 “dog years”), whereas mesothelioma in human asbestos exposure has a usual latency (time since asbestos exposure) in excess of 20 years.¹⁴

ACUTE TOXIC EXPOSURES

Accidental poisoning is a major cause of acute injury and death in the United States. The national network of poison control centers in the United States provides emergency advice to individuals and health care professionals about human poisonings (800–222–1222).¹⁵

Each year more than 2 million cases of acute toxic exposures are reported to regional poison control centers, and many others are treated in emergency departments without formal reporting.¹⁶ The majority of human poisonings involve young children, and the most common source of poisoning is from prescription medications. However, other common exposures include cleaning substances and pesticides. Table 8-2 shows the substances most commonly involved in human exposures reported to poison control centers.

Table 8-2 Top 25 Substances Involved in Human Exposures Reported to American Association of Poison Control Centers, 2006

Substance	No.	%*
Analgesics	284,906	11.9
Cosmetics/personal care products	214,780	8.9
Cleaning substances (household)	214,091	8.9
Sedative/hypnotics/antipsychotics	141,150	5.9
Foreign bodies/toys/miscellaneous	120,752	5.0
Cold and cough preparations	114,559	4.8
Topical preparations	108,308	4.5
Pesticides	96,811	4.0
Antidepressants	95,327	4.0
Bites and envenomations	82,133	3.4
Cardiovascular drugs	80,426	3.3
Alcohols	76,531	3.2
Antihistamines	75,070	3.1
Food products/food poisoning	66,115	2.8
Antimicrobials	66,017	2.7
Plants	64,236	2.7
Vitamins	63,331	2.6
Hormones and hormone antagonists	51,875	2.2
Gastrointestinal preparations	50,914	2.1
Hydrocarbons	49,526	2.1
Chemicals	47,557	2.0
Stimulants and street drugs	46,239	1.9
Anticonvulsants	40,476	1.7
Fumes/gases/vapors	39,586	1.6
Arts/crafts/office supplies	37,990	1.0

* Percentages are based on the total number of human exposures (2,403,539) rather than the total number of substances.

From Bronstein AC, Spyker DA, Cantilena LR Jr et al: 2006 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS), Clin Toxicol (Phil) 45(8):815-917, 2007.

Animals also experience acute poisoning episodes. In fact, a significant number of calls to human poison control centers involve nonhuman animals. As Table 8-3 shows, reported poisoning in dogs is much more frequent than in cats, and poisonings in other species, including livestock and wildlife, are much less likely to be reported.¹¹ In addition to animal reports to human poison control centers, acute poisoning episodes in animals are reported to veterinary practices and a network of animal poison control centers in the United States and other countries. The American Society for the Prevention of Cruelty to Animals (ASPCA) maintains the national Animal Poison Control Center, a 24-hour resource for practitioners managing acute toxic exposures in animals.¹⁷ An online information system has been developed in Switzerland for the management of poisoning in large and small animals (http://www.clinitox.ch).¹⁸ France also has a national service (http://www.vet-lyon.fr).¹⁹

Table 8-3 Nonhuman Exposures by Animal Type Reported to American Association of Poison Control Centers

Animal	No.	%
Dog	114,599	89.3
Cat	12,002	9.4
Bird	482	0.4
Rodent/lagomorph	417	0.3
Horse	264	0.2
Sheep/goat	105	0.1
Cow	41	0
Aquatic	40	0
Other	403	0.3
Total	128,353	100

Table 8-4 shows the distribution of substances accounting for toxic exposures in animals reported to poison control centers and veterinary practices in 2006. Chocolate ingestion, rodenticide exposure (also a hazard to children in a house), and medications (especially analgesics) account for the majority of animal poisoning reports. Animals can be exposed to pharmaceuticals from ingesting human medications that are left unsecured within a household and from inappropriate administration of human or veterinary medications by human beings. Inappropriate ingestion also accounts for much of exposure to rodenticides, pesticides (including slug bait), poisonous plants, and cleaning products.^20,²¹ An acute toxic poisoning in an animal can therefore be a warning sign of inappropriate access to hazardous products. This situation should alert human health and animal health care providers to take steps to avoid further pet or children’s exposures.

Table 8-4 Exposures of Animals to Various Toxic Agents Reported by Veterinary Clinics and Poison Control Centers

Agent	Relative Frequency (%)
Chocolate	26
Rodenticides	26
Pharmaceuticals	22
Pesticides	13
Plants	5
Miscellaneous	3
Glycols	1

Adapted from Gwaltney-Brandt SM: Epidemiology of animal poisonings. In Gupta RC (ed): Veterinary toxicology: basic and clinical principles, New York, 2007, Academic Press.

Clinical management of acute toxic exposures involves identification of the exposure, reduction of the exposure, administration of specific antidotes if available, and supportive care. In-depth discussion of treatment protocols for the complete range of specific chemical exposures is beyond the scope of this book, but a number of common toxic exposures found in homes are covered, in addition to those in the sections on carbon monoxide, lead poisoning, pesticides, envenomations, and HABs.

Common Medications and Their Toxicity in Human Beings and Animals

(From Peterson ME, Talcott PA: Small animal toxicology, ed 2, St Louis, 2006, Saunders Elsevier. Courtesy Dr. M. Kern.)

Table 8-5 Common Medications and Their Toxic Effects in Human Beings and Pets

Other Household/Environmental Sources of Acute Toxic Exposures

Ethylene Glycol

Ethylene glycol (EG) toxicosis is relatively common in both human beings and domestic animals, especially dogs and cats. The most common source is antifreeze, which is approximately 95% EG. Its sweet taste is attractive, and EG can be found stored in many households. Exposure is usually by ingestion, although cutaneous exposure has been reported to cause toxicity in cats.²²

Acute EG ingestion causes a toxicosis with CNS depression and gastric irritation. EG is metabolized in the liver by enzymes such as alcohol dehydrogenase to metabolites including glycoaldehyde and glyoxylate that can lead to further toxicity, including an anion gap metabolic acidosis, renal failure, and deposition of oxalic acid crystals in the kidney and other tissues.²³ Fomepizole (4-methylpyrazole) is an alcohol dehydrogenase inhibitor that is indicated for suspected or confirmed cases of EG (or methanol) toxicity in human beings.²⁴ It is also used in dogs. In cats, fomepizole is ineffective at the canine dosage and ethanol is used. Once renal failure develops in dogs and cats, the prognosis is poor. In contrast, the use of dialysis in human beings is one reason why renal insufficiency in EG poisoning has a relatively good prognosis.

Cleaning Products (Bleach, Ammonia, Others)

Cleaning products such as hypochlorite bleach and ammonia are toxic to animals and human beings through ingestion, inhalation of fumes, or skin contact. Ingestion by pets can occur through drinking from toilet bowls or other li-quids treated with cleaners and can lead to GI distress, including vomiting and irritation. Respiratory exposure can result in irritation and difficulty breathing and the development or worsening of asthma symptoms. Dermal exposure leads to an irritative dermatitis. Treatment involves removal from exposure, substitution with less-irritating chemical cleaning agents, and symptomatic treatment of airway, skin, or GI irritation.

Metaldehyde

Metaldehyde is a bait used to kill slugs, snails, and other garden pests. Baits in pellet form resemble dog food and are flavored with sweeteners such as molasses to attract snails. This can lead to poisoning in dogs, cats, birds, and other wildlife. Human poisoning can also occur, especially in children who accidentally ingest pellets, but such incidents are less common in human beings than in other animals. Human poisonings are usually not serious. Metaldehyde is a neurotoxin and exposure results in vomiting, tachycardia, tremors, seizures, and death.¹¹ Susceptibility varies slightly by species. Treatment involves removal of the agent from the GI tract, use of activated charcoal, and control of medical complications, including seizures and acidosis.

Poisonous Plants

A wide variety of plants used as houseplants or in home landscaping are toxic to human beings and other animals if they are ingested. Exposures to leaves, stems, and berries of poisonous plants are a significant cause of poisoning in animals and can also pose a risk to children. Each year more than 100,000 calls to poison control centers involve plant exposures.²⁵ Table 8-6 shows the most common types of plant exposures involved in human poison center calls.

Table 8-6 Top 25 Poisonous Plant Exposures Reported to American Association of Poison Control Centers, 2006

Botanical (Common) Name	No.
Spathiphyllum spp. (peace lily)	2133
Euphorbia pulcherrima (poinsettia)	1615
Ilex spp. (holly)	1572
Philodendron spp. (philodendron)	1514
Phytolacca americana (American pokeweed)	1358
Toxicodendron radicans (poison ivy)	1194
Schlumbergera bridgesii (Christmas cactus)	705
Ilex opaca (American holly)	608
Crassula argentea (jade plant)	604
Plants—cardiac glycosides	583
Malus spp. (crabapple)	582
Taraxacum officinale (dandelion)	581
Pepper mace	566
Epipremnum aureum (silver vine, money plant)	566
Plants—cyanogenic glycosides	555
Plants—pokeweed	543
Mold	538
Caladium spp. (elephant ear)	533
Nandina domestica	530
Narcissus pseudonarcissus (wild daffodil)	474
Spinacia oleracea (spinach)	467
Cactus (unknown type or name)	460
Rosa spp. (rose)	450
Quercus spp. (oak)	447
Hedera helix (common ivy)	446

Most poisonous plant exposures to human beings are non–life-threatening because the quantities ingested by children are usually small. Certain plants, however, have high levels of toxins. An example is poisonous oleander (Nerium oleander) (Color Plate 8-2). The leaves of the oleander plant contain cardiac glycoside chemicals resembling digoxin. The toxicity of oleander in human beings and other animals resembles digoxin toxicity, with GI distress, nausea, and tachycardia and other arrhythmias. Treatment is with the digoxin-specific Fab antibody fragment.²⁵

Ingestion of mushrooms and toadstools is another serious cause of plant poisonings in human beings and animals. The majority of human fatalities and serious dog poisonings as a result of mushroom poisoning involve mushrooms of the genus Amanita that contain Amanita toxin (Figure 8-4). Ingestion by human beings or animals leads to hepatocellular injury and liver and kidney failure. Puppies and children may be at increased risk. Treatment is supportive and involves gastric decontamination and activated charcoal for recent ingestion followed by management of medical complications.

Figure 8-4 Amanita rubescens.

(From Auerbach PS: Wilderness medicine, ed 5, Philadelphia, 2007, Mosby Elsevier.)

Rodenticides

Rodenticides, used to control rats and mice around dwellings, represent another example of a potent toxic hazard to which animals are more often exposed than human beings. Rodenticides are often placed near places where rodent infestation exists but where pets and wildlife may also have access. The toxic elements in rodenticides are anticoagulants, including warfarin and related compounds, that kill rodents by causing internal bleeding. The symptoms of rodenticide ingestion are bleeding complications, including hematomas (Color Plate 8-3), GI bleeding, hematuria, anemia, and prolongation of the international normalized ratio. Treatment consists of administration of vitamin K to reverse the warfarin effect on the coagulation pathway.

A newer rodenticide agent, bromethalin, is a neurotoxic agent that uncouples oxidative phosphorylation in the mitochondria of the CNS. Animals poisoned with bromethalin develop cerebral edema and neurological signs including ataxia and paralysis (Figure 8-5). Human cases are rare to date, but a fatality has been reported.²⁶ It is anticipated that treatment in human beings will be modeled after treatment in animals, including GI decontamination and treatment of cerebral edema.²⁶

Figure 8-5 Hindlimb ataxia with decreased conscious proprioception in a cat 5 days after ingestion of bromethalin (found in rodenticides) (dose 0.45 mg/kg).

(From Dorman DC: Emerging neurotoxicities. In August JR (ed): Consultations in feline internal medicine, vol 2, Philadelphia, 1994, WB Saunders.)

PTFE Fumes

Nonstick cooking pans containing PTFE (Teflon) release fumes (perfluorooctanoic acid [PFOA]) when overheated. These fumes are highly toxic to caged birds, and there are numerous reports of pulmonary hemorrhage and death. A syndrome known as polymer fume fever can develop in human beings exposed to fumes of burning PTFE and Teflon-containing sprays.^27,²⁸ Flulike symptoms of fever, chills, and cough have been reported. Treatment for inhalation of PTFE fumes is supportive.

Table 8-7 summarizes the comparative presentation and treatment of common toxic exposures in human beings and other animals. Consultation with a poison control center is recommended for serious acute poisoning exposures.

Table 8-7 Comparative Presentation and Treatment of Common Toxic Exposures in Human Beings and Other Animals

Identification of Exposure

Identification of the toxic exposure can involve checking product labels and searching online or through the distributing company for a copy of the material safety data sheet (MSDS) regarding the suspected chemical exposure (see the Resources section for Web site resources for MSDSs and other toxic hazards). During the medical evaluation of the exposure, specialized toxicologic testing may be indicated. Table 8-8 summarizes analytical toxicologic testing in animals. Similar testing can be performed in human beings.

Table 8-8 Samples That May Be Needed for Analytical Toxicology Testing*

In addition to eliminating the offending exposure and treating the patient, human health and veterinary clinicians can contact the environmental health officer in the local health department to report suspected environmental hazards to human beings or other animals.

A veterinarian who sees a pet animal with a toxic exposure that could also endanger the owner and family should consider directly contacting the human health care provider for the family to communicate this concern. Similarly, human health clinicians who identify environmental health hazards in the setting of pet ownership should counsel patients to contact their veterinarian or should contact the veterinarian directly.

CHRONIC TOXIC EXPOSURES AND HEALTH EFFECTS

Toxic exposures at levels below those associated with acute poisoning can produce long-term toxic effects in both human beings and other animals. Studies have linked certain low-dose household toxic exposures to chronic health effects in animals, suggesting that animals in a household could serve as sentinels for human beings exposed to the same substances.

Cancer

A number of studies have found associations between exposure to chemical and physical hazards and cancer in animals, especially in dogs. Table 8-9 lists some of these reported associations. Many of these associations are based on limited case-control studies or descriptive case reports and remain inconclusive. One obstacle to connecting animal cancers to environmental exposures is the existence of fewer tumor registries for domestic animals compared with human beings. Another is the lack of detailed data on environmental exposures; often data are not obtained for animals diagnosed with cancer. Much remains unknown regarding the linkages between animal risk and human risk of carcinogenesis, including reasons why the most common types and sites of cancer may vary among species and differing biology of particular cancers across species.¹² Therefore linking the occurrence of animal cancers to either environmental exposures or human risks remains extremely difficult.

Table 8-9 Reported Associations Between Cancer in Animals and Environmental Exposures

Nevertheless, considering the relationships between human and companion animal cancers may be of both clinical and scientific value. Dogs and human beings are the only animals that naturally develop lethal prostate cancers. Breast cancer in female dogs spreads to bone, just as it does in women. The most frequent tumor in dogs, osteosarcoma, is an important tumor that affects young people. Such observations have led to the development of the field of “comparative oncology.” A growing amount of research is studying similarities and differences between tumors of human beings and domestic animals, and new cancer registries for pet cancers are being established to better understand links between environments and cancers.³⁷ Some studies have attempted to assess human environmental cancer risk by monitoring biomarkers such as lymphocyte micronucleus testing in dogs living near Environmental Protection Agency (EPA) Superfund sites to determine the extent of exposure to mixtures of chemicals that could be carcinogenic.³⁸

When patients report a history of cancer in a pet, human health clinicians may wish to contact the veterinarian to determine whether a suspected environmental cause of a pet cancer exists. If there appears to be grounds for concern, the physician or veterinarian can contact the environmental health department of the local or state health department or one of the regional clinics in the Association of Occupational and Environmental Medicine Clinics (AOEC) to assess any possible human risk related to the exposures.

Noncancer Outcomes

Just as with cancer, a number of other diseases in animals have been attributed to chronic exposures to toxicants, and there is evidence that animals can serve as sentinels for human beings. Recently an association has been reported between hyperthyroidism in cats and high levels of the flame retardant polybrominated diphenyl ether (PBDE) related to house dust and diet exposures.³⁹ This association is an example of the current scientific controversy regarding the potential of chemicals in the environment to cause alterations in endocrine function (“endocrine disruption”) in animals and possibly human beings.

As previously described, cats were sentinels of methyl mercury poisoning in Minamata, Japan, and the deaths of dogs and horses provided warning of a human health risk from dioxin in oil sprayed for dust control in Times Beach, Missouri. Other examples of animals providing sentinel information about chronic toxic exposures in homes and outdoor environments include horses and deer that develop fluorosis of their bones and teeth while grazing near areas of fluoride-contaminated soil in the vicinity of aluminum smelters and other industrial sources (Figure 8-6).⁴⁰ In a similar fashion, livestock can develop signs of cadmium toxicity when grazing on cadmium-contaminated soils.⁴¹ Dogs have been used to monitor the effects of air pollution on lungs and cardiac function.⁴² Table 8-10 lists some of these reported associations between environmental toxic exposures and noncancer outcomes in animals that have potential sentinel value for human health.

Figure 8-6 Fluorosis in cheek teeth of a cow. The enamel is chalky and weak and the teeth are usually rapidly worn down.

(From McGavin MD, Zachary JF: Pathologic basis of veterinary disease, ed 4, St Louis, 2007, Mosby Elsevier. Courtesy Dr. L. Krook, College of Veterinary Medicine, Cornell University.)

Table 8-10 Noncancer Outcomes in Animals and Implicated Chronic Environmental Exposures

Species	Type of Disease	Exposure Implicated
Cat	Hyperthyroidism	Flame-retardant (PBDE) from carpet and furniture⁴³
Cat	Mercury poisoning	Fish consumption
Dog	Lung disease	Ambient air pollutants⁴²
Cattle, horses, deer	Fluorosis of bones and teeth	Exposure to fluoride in pastures contaminated from nearby factories
Horses, dogs	Sudden death	Exposure to dioxin from contaminated oil used to spray roads, stables⁸
Cattle	Cadmium-induced renal disease	Cadmium in feed and pastures irrigated with sewage sludge

References

1. U.S. Department of Housing and Urban Development. Healthy Homes Initiative, http://www.hud.gov/offices/lead/hhi/index.cfm. Accessed April 5, 2009

2. Burrell G, Seibert F. Experiments with small animals and carbon monoxide. J Ind Eng Chem. 1914;6(3):241-244.

3. Bukowski JA, Wartenberg D. An alternative approach for investigating the carcinogenicity of indoor air pollution: pets as sentinels of environmental cancer risk. Environ Health Perspect. 1997;105(12):1312-1319.

4. Eto K, Yasutake A, Nakano A, et al. Reappraisal of the historic 1959 cat experiment in Minamata by the Chisso Factory. Tohoku J Exp Med. 2001;194(4):197-203.

5. Thompson ME, Lewin-Smith MR, Kalasinsky VF, et al. Characterization of melamine-containing and calcium oxalate crystals in three dogs with suspected pet food-induced nephrotoxicosis. Vet Pathol. 2008;45(3):417-426.

6. Lattupalli R, Yee J, Kolluru A. Nephrotoxicity of mala fide melamine: modern era milk scandal. Scientific World Journal. 2008;8:949-950.

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10. Ginsberg G, Toal B. What’s toxic, what’s not. New York: Berkeley Books, 2006.

11. Gupta RC. Veterinary toxicology: basic and clinical principles. New York: Academic Press, 2007.

12. Kelsey JL, Moore AS, Glickman LT. Epidemiologic studies of risk factors for cancer in pet dogs. Epidemiol Rev. 1998;20(2):204-217.

13. Peterson ME, Talcott PA. Small animal toxicology, 2nd ed. St Louis: Saunders Elsevier, 2006.

14. Glickman LT, Domanski LM, MacGuire TG, et al. Mesothelioma in pet dogs with exposure of their owners to asbestos. Environ Res. 1983;32(2):305-313.

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20. Cope RB, White KS, More E, et al. Exposure-to-treatment interval and clinical severity in canine poisoning: a retrospective analysis at a Portland veterinary emergency center. J Vet Pharmacol Ther. 2006;29(3):233-236.

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23. Ford MD, Delaney KA, Ling L, et al. Clinical toxicology. Philadelphia: Saunders, 2001.

24. Holstege CP, Dobmeier SG, Bechtel LK. Critical care toxicology. Emerg Med Clin North Am. 2008;26(3):715-739. viii–ix

25. Froberg B, Ibrahim D, Furbee RB. Plant poisoning. Emerg Med Clin North Am. 2007;25(2):375-433.

26. Pasquale-Styles MA, Sochaski MA, Dorman DC, et al. Fatal bromethalin poisoning. J Forensic Sci. 2006;51(5):1154-1157.

27. Patel MM, Miller MA, Chomchai S. Polymer fume fever after use of a household product. Am J Emerg Med. 2006;24(7):880-881.

28. Son M, Maruyama E, Shindo Y, et al. Case of polymer fume fever with interstitial pneumonia caused by inhalation of polytetrafluoroethylene (Teflon) [in Japanese]. Chudoku Kenkyu. 2006;19(3):279-282.

29. Animal Forum. Animal poison control center offers pet poison safety tips for bird owners, http://www.animalforum.com/birdpoison.htm Accessed April 5 2009

30. Stoltz JH, Galey F, Johnson B. Sudden death in ten psittacine birds associated with the operation of a self-cleaning oven. Vet Hum Toxicol. 1992;34(5):420-421.

31. Snyder LA, Bertone ER, Jakowski RM, et al. P53 expression and environmental tobacco smoke exposure in feline oral squamous cell carcinoma. Vet Pathol. 2004;41(3):209-214.

32. Glickman LT, Raghavan M, Knapp DW, et al. Herbicide exposure and the risk of transitional cell carcinoma of the urinary bladder in Scottish Terriers. J Am Vet Med Assoc. 2004;224(8):1290-1297.

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34. Hayes HM, Tarone RE, Cantor KP, et al. Case control study of canine malignant lymphoma: positive association with dog owner’s use of 2,4-dichlorophenoxyacetic acid herbicides. J Natl Cancer Inst. 1991;83(17):1226-1231.

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CARBON MONOXIDE

Peter M. Rabinowitz, Lisa A. Conti

(ICD-10 T58.0 Toxic Effect of Carbon Monoxide)

Carbon monoxide (CO) is the most common cause of poisoning-related death.¹ Each year in the United States, several thousand individuals die or are hospitalized with CO poisoning related to smoke inhalation, and more than 400 deaths each year are attributed to non–fire-related accidental CO poisoning.² Because the gas has no warning odor or color and the symptoms are often subtle and nonspecific, the true incidence of CO poisoning in human beings may be much higher. In fact, CO has been termed the “unnoticed poison of the twenty-first century.”³ CO is an example of a toxicant for which companion animals could provide early warning of human exposure risk. However, it is likely that just as in human beings, the diagnosis is often overlooked. The classic animal sentinel for CO poisoning is the canary. Canaries were brought into mines in the United States and Great Britain in the first half of the twentieth century to provide early warning to miners of CO and other toxic gases. Canaries were chosen after experiments on this species, as well as guinea pigs, rabbits, chickens, dogs, mice, and pigeons, revealed that either canaries or mice were most suitable, with canaries more sensitive than mice to the effects of CO.⁴ Canaries developed recognizable signs of toxicosis sufficiently early to allow the miners to take preventive steps to avoid further exposure. In the home setting as well, dogs and cats may sometimes serve as sentinels. Human cases of CO poisoning have been detected because the family dog and family members were displaying signs of intoxication.⁵ Additionally, the 2007 ASPCA Cat of the Year award was given to a 2-year-old domestic short-hair cat that scratched at her sleeping owner’s face to arouse her and save her from death from CO intoxication.⁶

Key Points for Clinicians and Public Health Professionals

Public Health Professionals

• Educate the public on preventive measures (Box 8-1).

• Maintain heightened alertness at the onset of the winter heating season as well as after natural disasters and emergencies such as power outages, hurricanes, and earthquakes.

• Consider CO exposure in unexplained deaths of animals or human beings.

• Monitor poison control data.

• Consider adding CO intoxication as a reportable condition if it is not already.

BOX 8-1 You Can Prevent Carbon Monoxide Exposure

Modified from Centers for Disease Control and Prevention: Carbon monoxide poisoning: prevention guidelines. http://www.cdc.gov/co/guidelines.htm.

• Do have your heating system, water heater, and any other gas, oil, or coal-burning appliances serviced by a qualified technician every year.

• Do install a battery-operated CO detector in your home and check or replace the battery when you change the time on your clocks each spring and fall. (Some states have passed laws requiring their installation.⁷) If the detector sounds, leave your home immediately and call 911.

• Do seek prompt medical attention if you suspect CO poisoning and are feeling dizzy, lightheaded, or nauseated.

• Don’t use a generator, charcoal grill, camp stove, or other gasoline- or charcoal-burning device inside your home, basement, or garage or near a window.

• Don’t run a car or truck inside a garage attached to your house, even if you leave the door open.

• Don’t burn anything in a stove or fireplace that is not vented.

• Don’t heat your house with a gas oven.

AGENT

CO is an odorless, colorless, nonirritating gas that is produced by the incomplete combustion of fuels. Common sources include malfunctioning and improperly vented heating furnaces, automobile exhaust, and propane-powered equipment such as forklifts, generators, space heaters, and floor polishers (Figure 8-7).⁸ CO is also a component of air pollution, leading to population-wide low-level exposures. CO is slightly lighter than air, so it tends to rise through a building.

Figure 8-7 CDC flyer on the proper use of generators and pressure washers.

(From Centers for Disease Control and Prevention, Atlanta, Ga.

ROUTES OF EXPOSURE AND METABOLIC FATE

The primary route of CO exposure is inhalation. Levels of CO in ambient air are usually less than 10 ppm but may be higher in urban areas. The Occupational Safety and Health Administration (OSHA)-permissible exposure level for CO exposures in the workplace is 50 ppm. After a gas stove is used for cooking, nearby air levels may exceed 100 ppm.¹ CO inhaled into the lungs binds tightly to hemoglobin in red blood cells (RBCs) to form carboxyhemoglobin (COHb). This process displaces oxygen from the hemoglobin-binding sites because it binds to hemoglobin more than 200 times more avidly than oxygen.³ This reduces the oxygen-carrying capacity of the bloodstream, causing tissue hypoxia, particularly of the heart and brain. COHb is bright red in color, which is why tissues of a CO-poisoned individual may be “cherry red.” The half-life of COHb in the human bloodstream is approximately 4 to 5 hours when the person is breathing room air. However, if 100% oxygen is administered, the half-life has been reported to shorten to 47 to 80 minutes⁹ and is even shorter in a hyperbaric oxygen environment.

The level of COHb in the blood helps determine the degree of toxicity. Smokers may have chronically elevated levels around 7% to 12%. Normal levels in nonsmokers are generally less than 2%.¹⁰

GROUPS AT RISK

Individuals at high risk of CO poisoning include workers who use propane- or gasoline-powered equipment and individuals who improperly use propane- or gasoline-fired generators, space heaters, or other heating devices, including wood- and coal-burning stoves. Use of such equipment may increase in areas that have experienced natural disasters. Individuals with increased susceptibility include elderly people, individuals with cardiovascular disease, infants, and pregnant women (risk to the fetus).

Pets such as dogs may be at increased exposure risk relative to human beings because of their faster breathing rate and smaller volume of distribution. Birds have increased susceptibility relative to human beings because of their efficient gas exchange and higher mass-specific ventilation of tissues.¹¹ Pregnant animals and pets with underlying cardiac disease are at increased risk.

TOXICITY IN HUMAN BEINGS

CO can produce both acute and chronic effects (Figures 8-8 and 8-9).³ Because of their high metabolic activity and oxygen demand, the brain and heart are the organs most affected by exposure. Low-level chronic exposure, as from a slowly leaking furnace, can cause headaches, fatigue, malaise, dizziness, chest pain, and abdominal pain. These nonspecific symptoms can easily be attributed to other causes, and the diagnosis may therefore be overlooked. Elevations in the COHb level to between 5% and 20% may be associated with subtle changes such as headache and behavioral changes. Chronic exposures are believed to predispose human beings to the development of cardiovascular disease and memory loss.

Figure 8-8 Effects of carboxyhemoglobin (COHb) on oxygen dissociation from hemoglobin (A), and the symptoms associated with carbon monoxide (CO) poisoning (B). The affinity of CO for hemoglobin (Hb) is 220 times higher than for oxygen, thereby decreasing the oxygen-carrying capacity of blood. In addition, COHb shifts the oxyhemoglobin–oxygen saturation curve to the left, making oxygen release during hypoxia more difficult. This is illustrated in the upper panel, which is normalized to 100% maximum. If the data were expressed as absolute oxygen content, the values in the presence of COHb would be decreased compared with normal.

(From Page CP, Hoffman B, Curtis M et al: Integrated pharmacology, ed 3, Edinburgh, 2006, Mosby Elsevier.)

Figure 8-9 Magnetic resonance imaging of the brain shows areas of infarction after carbon monoxide poisoning. This T2-weighted image shows abnormally high signal intensity in the basal ganglia, right frontal lobe, and cerebral cortex.

(From Yanoff M, Duker J: Ophthalmology, ed 2, St Louis, 2004, Mosby.)

Acute, high-level exposure with COHb levels greater than 20% produces symptoms as described above, as well as ataxia, confusion, slurred speech, disturbances of visual or auditory function and, with increasing intoxication, eventual loss of consciousness. If exposure continues, death can result from respiratory arrest (Color Plate 8-4). The skin color of CO-poisoned individuals usually is normal. The pulse oximetry reading can be falsely elevated because conventional oximeters cannot distinguish between oxyhemoglobin and COHb. There may be electrocardiographic abnormalities including arrhythmias and ischemia. Magnetic resonance imaging (MRI) of the brain may show white matter high-signal intensities resulting from impaired diffusion.³ Low-attenuation lesions in the globus pallidum have been reported.

Individuals who have recovered from acute episodes of intoxication may have long-term sequelae including chronic encephalopathy, parkinsonism, memory loss, and other signs of dementia.

TOXICITY IN ANIMALS

Dogs appear to be more resistant to COHb than human beings.¹³ Acute signs include lethargy, incoordination, cherry-red mucous membranes, dyspnea, coma, and death. Tachycardia has been reported in dogs at levels of 15% COHb.¹⁴ Chronic exposure in dogs and cats can manifest as decreased exercise tolerance and gait problems.

Birds exhibit drowsiness, difficulty breathing, weakness, ataxia, and seizures.¹¹ Chickens may become exposed in enclosed facilities and during transport in trucks. This can result in high mortality rates, with bright pink coloration of the viscera at necropsy.¹⁵ Spontaneous abortion has been noted in sows that have experienced CO intoxication.¹² Table 8-11 shows key aspects of CO toxicity in human beings and other animals.

Table 8-11 Comparative Toxicity of Carbon Monoxide in Human Beings and Other Animals

DIAGNOSIS

The cornerstone of diagnosis is the history of exposure and a COHb level. The COHb level should be measured as soon as the diagnosis is suspected because the half-life is 4 to 5 hours. A history of similar illness resembling CO intoxication in both animals and people is supportive of the diagnosis.

Measurement of air levels of CO in the area where the exposure occurred should also be done as soon as possible. Many fire departments or public health departments are able to obtain such measurements. Although CO standards have yet to be set for indoor air, the U.S. National Ambient Air Quality Standards are 9 ppm for 8 hours and 35 ppm for 1 hour for outdoor air.¹⁸

MANAGEMENT OF CO POISONING

Treatment in Human Beings

The principal approach to management of acute CO poisoning is to remove the patient from exposure, ensure adequate oxygenation, and eliminate COHb from the body (Figure 8-10). All patients should receive 100% oxygen. Patients with significant symptoms (such as loss of consciousness with or without neurological deficits) levels of COHb greater than 25% and all pregnant patients are candidates for hyperbaric oxygen therapy, but hyperbaric oxygen therapy should be considered on a case-by case-basis in all patients in consultation with a bariatric medicine specialist.