See individual topic discussions on absorption, distribution, metabolism, and excretion (ADME), mechanisms of action, systems affected and diagnostic approaches for individual toxicants.

       History and clinical signs should be kept in perspective for determining differential diagnoses while completing the necropsy.

       Poisonings often affect many animals in a very short period of time and thus attract substantial public attention and interest.

       Many clues can increase the suspicion of a toxic etiology. Obvious cases involve sudden onset of disease in a number of animals. Common feed or environmental conditions will further support a suspicion of an intoxication. Intoxication is also suggested in the otherwise healthy animal that is found “suddenly dead”.

       However, chronic and subchronic intoxications also occur and are more challenging to diagnose because they are subtle. Sporadic mortality in a group of animals along with poor animal condition should raise suspicion of a chronic intoxication.

       Other situations suggesting testing from a toxicology laboratory include drug testing in the racehorse industry, testing for nutritional adequacy (especially selenium and vitamin E status), or providing testing in suspect cases of malicious poisoning.

       Reasons to suspect a poisoning:Many animals are sick with no known exposure to infectious disease.Affected individuals have been exposed recently to a new environment.There has been a recent change in feed.Recent construction activity in the environment.Recent pesticide application in the environment.Unusual weather conditions.The animal has limited feed or pasture, resulting in consumption of plants not normally consumed.An uncommon clinical condition exists.There has been a potential threat of malicious poisoning.Unexplained death(s) has/have occurred.Persistent poor health condition.

       Toxicants typically target specific organs or systems (e.g. the cardiovascular, the nervous or the urogenital systems). However, multiple organs can be affected.

       If a toxicant targets a specific organ this can help narrow down the differential list.

       However, many toxicants target the same organ or system, likely causing similar clinical signs. Therefore, one should not rely on clinical signs alone to make a diagnosis.

       Templates can be useful guides for collecting diagnostic information (see Table 2.1), but no template can possibly account for all scenarios. Thus, a thorough, thoughtful and organized investigation is needed without over‐reliance on a template.

       Establishing an accurate diagnosis depends heavily on a systematic approach because toxicants often have clinical signs that overlap with other non‐toxicologic causes and lesions may or may not be present.

       Even if a poisoning is suspected, the practitioner has to be a neutral observer considering toxic as well as non‐toxic causes of disease. For example, lead poisoning may cause few or very subtle lesions while oak or monensin intoxications cause consistent lesions helpful for making a diagnosis.

       The absence of lesions is as important as their presence and is helpful in narrowing down a differentials list.

       An accurate diagnosis is central to providing adequate treatment for affected animals and preventing new cases.TABLE 2.1. Checklist for information collection in a suspected poisoning.Owner Data: Date:__________________________________ Owner:________________________________ Manager:______________________________ Address:_______________________________ Phone:______________________________ __ Fax:___________________________________ E‐mail:_________________________________ Health History:Illness past 6 monthsExposure to other animals last 30 daysVaccination historyMedications: sprays, dips, hormones, minerals, wormers past 6 monthsLast exam by a veterinarianPatient Data: Species: __________________________________ Breed:____________________________________ Sex:______________________________________ Pregnancy:_________________________________ Weight:____________________________________ Age:______________________________________ Current Clinical History:Herd size; housingAre other similar groups on the same premises?Common feed or water among groups?Morbidity___________ Mortality _________When first observed sick?How long has problem been in the herd?If found dead, when last seen alive and healthy?Any recent malicious threats?Environmental Data:Location: pasture, woods, dry lot, near river or pond, confined indoors; recent location changesHousing: group‐housed or individually; type of ventilation; new constructionRecent changes in weather, transport, shows or competitions; unexplained deaths; access to trash, old construction materials; recent burning of materialsPesticide use (i.e. insecticides, rodenticides, herbicides) and specific types or names if available (ask for tags or bags to ID)Materials used for construction/renovationServices such as lawn care, pasture seeding, tree planting, and fertilizationAccess to old machinery, automotive products, treated lumber, burn piles, flowing waterDietary Data:Nutritionist (contact information)Diet components: whole grains or ground; sweet feed; pelleted complete feed; other (list)Recent changes in total diet or specific diet component(s)Method of feeding (hand feeding, full feed, mechanical delivery)Type of hay (e.g. grass, alfalfa, mixed; weed contaminants)Presence of molded or spoiled feed or hayPasture: type, scant, abundant, weed contamination; trees or brush presentWater source (flowing stream, pond, well, county or city water)Clinical Signs: Ataxia Salivation Blindness/vision Depression Excitement Seizures Cerebellar signs Dysphonia Other (describe) Anorexia Colic Vomiting Diarrhea Melena Polyphagia Polydipsia Polyuria Dyspnea Lameness Anemia Hemorrhage Hematuria Icterus Hemoglobinuria Methemoglobinemia Straining Fever Weakness Alopecia

       A conclusive diagnosis depends heavily on a systematic investigation, appropriate sample choice based on a good knowledge of ADME and appropriate sample handling and storage to preserve specimen integrity.

       Discriminating between differential diagnoses may require ancillary diagnostics:Histopathology:Samples for histopathology should be collected in 10% formalin.Bouin’s solution can be used for delicate tissues (i.e. ophthalmic, gastrointestinal and reproductive tissues). Bouin’s solution is not a good fixative for preserving ultrastructure for electron microscopy.Tissues should not exceed 0.5 cm thickness to permit proper fixation. Bloody tissues (i.e. liver and spleen) should be thinner.A set of samples should minimally include liver, kidney, lungs, GI tract and any tissues with lesions.Brain and/or spinal cord are needed if there are neurologic signs.Do not freeze formalin‐preserved tissues.Microbiology:Sterile culture swabs or large sections of any tissues with lesions should be sent fresh (refrigerated, not frozen) for microbial work‐up.Serology/immunology:Whole bloodSerumPlasmaMolecular diagnostics:1 cm square section of fresh (unfixed) tissue with the lesion in a sterile container refrigerated or frozen depending on transport time.Analytical toxicology:Use laboratories accredited by the American Association of Veterinary Laboratory Diagnosticians (AAVLD). These can be accessed at https://www.aavld.org/accredited‐labsFreeze appropriate unfixed tissue specimens for toxicology testing.Use separate containers for each specimen (i.e., do not combine samples into one container). Label each sample.If in doubt, contact the toxicology laboratory for advice on sample types and amounts, including collection and preservation of environmental