toxo model cram

Question 1

Toxicant:

ii. Toxin:

Answer 1

Toxicant: man made poison introduced into the environment

ii. Toxin: natural poison produced by a living organism

Question 2

Toxicity

. Toxicosis:

Answer 2

Toxicity: the amount or degree of toxin/toxicity it takes to damage an
organism
iv. Toxicosis: disease state induced by the toxin/toxicant

Question 3

Toxicology

Nanotoxicology

Answer 3

Toxicology: the branch of science which studies nature, effects, and
detection of poisons
vi. Nanotoxicology: Branch of toxicology which studies the toxicity of
nanoparticles (ultrafine particle between 1-100 nanometres in diameter)

Question 4

dose/response:

Answer 4

dose/response: any increase in dose will cause a graded increase in
response
1. There are two types of dose-response curves
a. one that describes the graded responses of an individual
to varying doses of the chemical
b. one that describes the distribution of responses to
different doses in a population of individuals

Question 5

NOAEL:

LOAEL

Answer 5

NOAEL: No observed adverse effect level

iii. LOAEL: Lowest observed adverse effect level

Question 6

LC50:
LD50:

Answer 6

LC50: Lethal Concentration 50- concentration required to kill 50% of the
population
v. LD50: Lethal dose 50- dose at which 50% of population dies

Question 7

Acute toxicology

Answer 7

Acute toxicology

1. Adverse effects of a substance from an exposure for <24hrs
   a. Sub-acute=> 24 hours- 1 month

Question 8

Chronic toxicology

Answer 8

Chronic toxicology
a. Adverse effects of a substance from an exposure for >3
months
1. Sub chronic= >1-3 months

Question 9

toxic endpoint

Answer 9

A toxic endpoint is the result of a study conducted to determine how
dangerous a substance is. The data collected from such studies are used
to report the relative toxicity of the compound to various regulatory
agencies and environmental compliance groups. Toxic endpoints can
include mortality, behavior, reproductive status or physiological and
biochemical changes.

Question 10

Developmental toxicity

Answer 10

Developmental toxicity focuses on pre-natal development of the
embryo or fetus. Toxicity may manifest as death of the embryo or
fetus, abnormal development or birth defects or retardation of
normal growth patterns

Question 11

Reproductive toxicity

Answer 11

Reproductive toxicity looks at all aspects of fertility. This includes
the reproductive cycle, sexual behavior, gamete (sperm or egg)
production and transport, fertility (including sperm quality and
quantity), pregnancy outcomes, gestation, childbirth, lactation and
maternal behavior. These studies also examine postnatal survival,
growth and development of offspring. Some studies look at
multiple generations to detect heritable effects.

Question 12

DART studies (developmental and repro studies)

Answer 12

DART studies are conducted to ensure the safety of new life-saving drugs
before they go on the market. They are also used to determine the safety
of pesticides and other household or industrial chemicals. Results of
these studies are used to develop safety guidelines to reduce exposure
risks for different populations, including pregnant women, infants and
young children.
ii. Different types of studies are used to evaluate different aspects of
reproduction and development. Generally, DART studies can be divided
into two types, which can sometimes be combined. (developmental and reproductive)

Question 13

Regulatory Requirements for DART Studies

Answer 13

Regulatory Requirements for DART Studies
1. In the U.S., the Food and Drug Administration (FDA) and Environmental Protection Agency (EPA) have established guidelines for DART studies required for product registration and
approval. Similar regulations are in place in the European Union
(EU) and many other regions around the world. Companies must
present data from DART studies conducted per applicable
regulatory guidelines in order to market and use their products in
these countries.

Question 14

Pharmaceuticals, DART studies reg requirements

Answer 14

Pharmaceuticals: In the U.S., the FDA approves pharmaceuticals
before they can be marketed. The toxicity tests that are required in
the U.S. are dictated by test guidelines put forth by the
International Conference on Harmonization (ICH).

Question 15

Three DART tests are required for small molecule pharmaceuticals:

Answer 15

Three DART tests are required for small molecule pharmaceuticals:
Embryo-Fetal Development (EFD),
Fertility and Early Embryonic Development (FEED) and a Pre- and Postnatal Development study (PPN). Combination studies may be performed to reduce the number of animals needed and to obtain results more quickly. (This should be
decided on a case-by-case basis, as it may not be appropriate for a given drug.) For large molecule biopharmaceuticals, such as vaccines and
proteins, other laboratory animal species and study designs may be used.

Question 16

Pesticides and Industrial Chemicals:

DART testing

Answer 16

Pesticides and Industrial Chemicals: Pesticides and industrial chemicals must also undergo DART testing to detect toxicity to the reproductive
system, including prenatal and postnatal development of the offspring. In the U.S., the EPA requires DART testing for product registration of
pesticides . For industrial chemicals, testing requirements are regulated by
the EPA’s Toxic Substance Control Act (TSCA). The EU has similar DART testing requirements for registration of pesticides and industrial
chemicals, which are described in the test guidelines put forth by the Organization for Economic Cooperation and Development (OECD).
Required DART studies depend on the chemical substance and its intended use and may include developmental toxicity, one- and two-generation reproductive toxicity studies, the extended one-generation reproduction study or reproductive screening tests.

Question 17

Target site resistance

Answer 17

Target site
1. Historically, the type of resistance that farmers and researchers deal with most often is target-site resistance. Every herbicide has a specific target site in a plant. The herbicide has to bind to that
target site and effectively shut it down in order to kill the weed.
Resistance can occur when changes in the target site stop the herbicide from effectively binding there. One change to the amino acid residue chain in the protein sequence, and all of the sudden you have resistance.”

Target-site mutations are often prompted by repeated applications of the same herbicide site of action. Today, target-site resistance remains the most common type of herbicide resistance seen around the world, encompassing resistance to ALS inhibitors,
ACCase inhibitors and more.

Question 18

Non-Target-Site resistance

Answer 18

Non-Target-Site
1. On the other end of the spectrum, non-target-site resistance, or metabolic resistance, involves more change in the plant than just at the target site alone. In this type of resistance, weeds develop
the ability to rapidly metabolize, or break down, the herbicide before it can cause significant biotoxic effects to the weed. Once an herbicide is inside a plant, it’s going to try and control it,” says
Hager. “With metabolic resistance, the weed is now behaving like the resistant crop and can rapidly metabolize the herbicide and survive.”
2. Though less common than target-site resistance, metabolic resistance is a concern on the rise.

Question 19

Mixed associations

Answer 19

Mixed associations

1. But whether you’re dealing with target-site resistance or non-target-site resistance, the control method remains the same: tank-mixing multiple herbicide modes of action in each application.
2. The probability that a weed will be resistant to two different herbicides combined is less than the probability of the weed being resistant to each herbicide individually.

Question 20

DNA adduct

Answer 20

A DNA adduct is a segment of DNA bound to a cancer-causing chemical .
This process could be the start of a cancerous cell, or carcinogenesis .
DNA adducts in scientific experiments are used as biomarkers of exposure and as such are themselves measured to reflect quantitatively, for comparison, the amount of carcinogen exposure to the subject
organism. Under experimental conditions for study, such DNA adducts are induced by known carcinogens , of which commonly used is DMBA ( 7,12-dimethylbenz(a)anthracene ). The presence of such an adduct indicates prior exposure to a potential carcinogen, but does not by itself
indicate the presence of cancer in the subject animal.

Question 21

ADME (Absorption, distribution, metabolism, excretion)= Acronym used to describe pharmacokinetics

Answer 21

Absorption- describes the journey of drug traveling from the site of
administration to the site of action
ii. Distribution- describes reversible transfer of the drug from one location to
another within the body
iii. Metabolism= conversion and breakdown of the drug within the body
iv. excretion= process by which metabolic waste is eliminated from an
organism

Question 22

Environmental Protection Agency :

Answer 22

Environmental Protection Agency : an independent executive agency, not a Department. The
administrator is a member of the Cabinet

Question 23

Toxic

Substances Control Act TSCA

Answer 23

The Toxic Substances Control Act of 1976 provides EPA with authority to require reporting, record-keeping
and testing requirements, and restrictions relating to chemical substances and/or mixtures.
Certain substances are generally excluded from TSCA, including, among others, food, drugs,
cosmetics and pesticides. TSCA addresses the production, importation, use, and disposal of
specific chemicals including polychlorinated biphenyls (PCBs), asbestos, radon and lead-based
paint.”

Question 24

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)

Answer 24

The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) provides for federal regulation
of pesticide distribution, sale, and use. All pesticides distributed or sold in the United States
must be registered (licensed) by EPA. Before EPA may register a pesticide under FIFRA, the
applicant must show, among other things, that using the pesticide according to specifications
“will not generally cause unreasonable adverse effects on the environment.’’ FIFRA defines the
term ‘‘unreasonable adverse effects on the environment’’ to mean: ‘‘(1) any unreasonable risk to
man or the environment, taking into account the economic, social, and environmental costs and
benefits of the use of any pesticide, or (2) a human dietary risk from residues that result from a
use of a pesticide in or on any food inconsistent with the standard under section 408 of the
Federal Food, Drug, and Cosmetic Act.’’

Question 25

Resource Conservation and Recovery Act (RCRA)

Answer 25

Resource Conservation and Recovery Act (RCRA) gives EPA the authority to control hazardous waste from the "cradle-to-grave." This includes the generation, transportation, treatment, storage, and disposal of hazardous waste. RCRA also set forth a framework for the management of non-hazardous solid wastes. The 1986 amendments to RCRA enabled EPA to address environmental problems that could result from underground tanks storing petroleum and other hazardous substances. HSWA - the Federal Hazardous and Solid Waste Amendments - are the 1984 amendments to RCRA that focused on waste minimization and phasing out land disposal of hazardous waste as well as corrective action for releases. Some of the other mandates of this law include increased enforcement authority for EPA, more stringent hazardous waste management standards, and a comprehensive underground storage tank program.

Question 26

Clean Air Act (CAA)

Answer 26

The Clean Air Act (CAA) is the comprehensive federal law that regulates air emissions from stationary and mobile sources. Among other things, this law authorizes EPA to establish National Ambient Air Quality Standards (NAAQS) to protect public health and public welfare and to regulate emissions of hazardous air pollutants.”

Question 27

Clean Water Act (CWA)

Answer 27

“The Clean Water Act (CWA) establishes the basic structure for regulating discharges of pollutants into the waters of the United States and regulating quality standards for surface waters. The basis of the CWA was enacted in 1948 and was called the Federal Water Pollution Control Act, but the Act was significantly reorganized and expanded in 1972. "Clean Water Act" became the Act's common name with amendments in 1972. Under the CWA, EPA has implemented pollution control programs such as setting wastewater standards for industry. EPA has also developed national water quality criteria recommendations for pollutants in surface waters. The CWA made it unlawful to discharge any pollutant from a point source into navigable waters, unless a permit was obtained. EPA's National Pollutant Discharge Elimination System (NPDES) permit program controls discharges. Point sources are discrete conveyances such as pipes or man-made ditches. Individual homes that are connected to a municipal system, use a septic system, or do not have a surface discharge do not need an NPDES permit; however, industrial, municipal, and other facilities must obtain permits if their discharges go directly to surface waters”.

Question 28

Safe Drinking Water Act (SDWA)

Answer 28

The Safe Drinking Water Act (SDWA) was established to protect the quality of drinking water in the U.S. This law focuses on all waters actually or potentially designed for drinking use, whether from above ground or underground sources. The Act authorizes EPA to establish minimum standards to protect tap water and requires all owners or operators of public water systems to comply with these primary (health-related) standards. The 1996 amendments to SDWA require that EPA consider a detailed risk and cost assessment, and best available peer-reviewed science, when developing these standards. State governments, which can be approved to implement these rules for EPA, also encourage attainment of secondary standards (nuisance-related). Under the Act, EPA also establishes minimum standards for state programs to protect underground sources of drinking water from endangerment by underground injection of fluids.”

Question 29

Animal Feeding | Operations (AFOs)

Answer 29

Animal Feeding Operations (AFOs) are agricultural operations where animals are kept and raised in confined situations. An AFO is a lot or facility (other than an aquatic animal production facility) where the following conditions are met: animals have been, are, or will be stabled or confined and fed or maintained for a total of 45 days or more in any 12-month period, and crops, vegetation, forage growth, or post-harvest residues are not sustained in the normal growing season over any portion of the lot or facility. AFOs that meet the regulatory definition of a concentrated animal feeding operation (CAFO) are regulated under the NPDES permitting program. The NPDES program regulates the discharge of pollutants from point sources to waters of the United States. CAFOs are point sources, as defined by the CWA. To be considered a CAFO, a facility must first be defined as an AFO, and meet the criteria established in the CAFO regulation”.

Question 30

Comprehensive Environmental Response, Compensation, and | Liability Act -- otherwise known as CERCLA

Answer 30

“The Comprehensive Environmental Response, Compensation, and Liability Act -- otherwise known as CERCLA or Superfund -- provides a Federal "Superfund" to clean up uncontrolled or abandoned hazardous-waste sites as well as accidents, spills, and other emergency releases of pollutants and contaminants into the environment. Through CERCLA, EPA was given power to seek out those parties responsible for any release and assure their cooperation in the cleanup. EPA cleans up orphan sites when potentially responsible parties cannot be identified or located, or when they fail to act. Through various enforcement tools, EPA obtains private party cleanup through orders, consent decrees, and other small party settlements. EPA also recovers costs from financially viable individuals and companies once a response action has been completed. EPA is authorized to implement the Act in all 50 states and U.S. territories. Superfund site identification, monitoring, and response activities in states are coordinated through the state environmental protection or waste management agencies. The Superfund Amendments and Reauthorization Act (SARA) of 1986 reauthorized CERCLA to continue cleanup activities around the country. Several site-specific amendments, definitions clarifications, and technical requirements were added to the legislation, including additional enforcement authorities. Also, Title III of SARA authorized the Emergency Planning and Community Right-to-Know Act (EPCRA).”

Question 31

Emergency Planning & Community Right-to-Know Act (EPCRA)

Answer 31

“Authorized by Title III of the Superfund Amendments and Reauthorization Act (SARA), the Emergency Planning & Community Right-to-Know Act (EPCRA) was enacted by Congress as the national legislation on community safety. This law is designed to help local communities protect public health, safety, and the environment from chemical hazards. To implement EPCRA, Congress requires each state to appoint a State Emergency Response Commission (SERC). The SERCs are required to divide their states into Emergency Planning Districts and to name a Local Emergency Planning Committee (LEPC) for each district. Broad representation by fire fighters, health officials, government and media representatives, community groups, industrial facilities, and emergency managers ensures that all necessary elements of the planning process are represented.” Key areas: Emergency planning, emergency release notification, hazardous chemical storage reporting requirements, and toxic chemical release inventory.

Question 32

Pollution | Prevention Act PPA

Answer 32

The Pollution Prevention Act focused industry, government, and public attention on reducing the amount of pollution through cost-effective changes in production, operation, and raw materials use. Opportunities for source reduction are often not realized because of existing regulations, and the industrial resources required for compliance, focus on treatment and disposal. Source reduction is fundamentally different and more desirable than waste management or pollution control. Source reduction refers to practices that reduce hazardous substances from being released into the environment prior to recycling, treatment or disposal. The term includes equipment or technology modifications, process or procedure modifications, reformulation or redesign of products, substitution of raw materials, and improvements in housekeeping,

Question 33

National Response | Center (NRC)

Answer 33

The National Response Center (NRC) is a part of the federally established National Response System and staffed 24 hours a day by the U.S. Coast Guard. It is the designated federal point of contact for reporting all oil, chemical, radiological, biological and etiological discharges into the environment, anywhere in the United States and its territories. The NRC also takes maritime reports of suspicious activity and security breaches within the waters of the United States and its territories. Reports to the NRC activate the National Contingency Plan and the federal government's response capabilities. It is the responsibility of the NRC staff to notify the pre-designated On-Scene Coordinator assigned to the area of the incident and to collect available information on the size and nature of the release, the facility or vessel involved, and the party(ies) responsible for the release. The NRC maintains reports of all releases and spills in a national database.”

Question 34

Department of Health and Human Services : FDA FFDCA Federal Food, Drug, and Cosmetic Act (FFDCA)

Answer 34

“Section 408 of the Federal Food, Drug, and Cosmetic Act (FFDCA) authorizes EPA to set tolerances, or maximum residue limits, for pesticide residues on foods. In the absence of a tolerance for a pesticide residue, a food containing such a residue is subject to seizure by the government. Once a tolerance is established, the residue level in the tolerance is the trigger for enforcement actions. That is, if residues are found above that level, the commodity will be subject to seizure. In setting tolerances, EPA must make a finding that the tolerance is "safe." Safe is defined as meaning that there is a "reasonable certainty that no harm will result from aggregate exposure to the pesticide residue." To make the safety finding, EPA considers, among other things: the toxicity of the pesticide and its break-down products, aggregate exposure to the pesticide in foods and from other sources of exposure, and any special risks posed to infants and children. Some pesticides are exempted from the requirement to have a tolerance. EPA may grant exemptions in cases where the pesticide residues do not pose a dietary risk under reasonably foreseeable circumstances.”

Question 35

Department of Health and Human Services : FDA Food Quality Protection Act (FQPA)

Answer 35

The Food Quality Protection Act (FQPA) was passed unanimously by Congress and then signed into law by President Clinton on August 3, 1996. The FQPA amended the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food Drug and Cosmetic Act (FFDCA) and thus fundamentally changed EPA’s regulation of pesticides. With regard to tolerances, the FQPA requires that EPA: -make a safety finding when setting tolerances, i.e., that the pesticide can be used with “a reasonable certainty of no harm;” use this new safety standard to reassess, over a 10-year period, all pesticide tolerances that were in place when the FQPA was signed; -consider the special susceptibility of children to pesticides by using an additional tenfold (10X) safety factor when setting and reassessing tolerances unless adequate data are available to support a different factor; -consider aggregate risk from exposure to a pesticide from multiple sources (food, water, residential and other non-occupational sources) when assessing tolerances; and -consider cumulative exposure to pesticides that have common mechanisms of toxicity. To implement these FQPA requirements, EPA needed to develop methodologies to perform more refined pesticide risk assessments, to better reflect real-world situations. Thus, in a short timeframe, EPA had to develop a variety of new science policies, which included new guidelines on: -Use of the 10X safety factor. -Drinking water exposure. -Residential exposure. -Aggregate exposure and risk assessment. -Cumulative risk assessment for pesticides with a common mechanism of toxicity. Using these newly-developed methodologies, EPA completed the reassessment of the 9,721 pesticide tolerances during the 10-year timeframe, as required. As a result, EPA revoked or modified almost 4,000 tolerances. The FQPA also required EPA to: -Expedite approval of pesticides meeting the FQPA definition of reduced risk. -Give special consideration to minor uses of pesticides (i.e., uses for which pesticide product sales produce small revenues and thus, the registrant might decide to not generate the data needed to support the minor use). -Provide a list of pests of significant public health importance (issued in 2002). -Expedite the review of applications to register antimicrobial pesticide products. -Screen pesticides for disruption to the endocrine system. -Significantly, FQPA requires the periodic review cycle for pesticide registrations. Changes in science and pesticide practices occur over time, and these periodic review cycles make sure that as changes occur, pesticide products can continue to be used safely. The Registration Review Program began in 2006 with the goal of reviewing each pesticide’s registration every 15 years to make sure that the pesticide still meets the FIFRA standards for registration.”

Question 36

DHHS CDC/ATSDR Agency for Toxic Substances and Disease Registry (ATSDR),

Answer 36

“ATSDR protects communities from harmful health effects related to exposure to natural and man-made hazardous substances. We do this by responding to environmental health emergencies; investigating emerging environmental health threats; conducting research on the health impacts of hazardous waste sites; and building capabilities of and providing actionable guidance to state and local health partners.”

Question 37

Heavy metals

Answer 37

Heavy metals (e.g. arsenic, copper, chromium, lead, mercury, iron, zinc)

Question 38

Arsenici. Sources in environment:

Answer 38

i. Sources in environment: ores, low levels in soil, except around mining/ smelting sites ii. Inorganic form- most toxic (trivalent form is more toxic than pentavalent form)

Question 39

Arsenici.Exposure

Answer 39

iii. Exposure 1.Old pesticides, arsenic contaminated soil, contaminated water, ant baits, thiacetarsamide/ heartworm trt, overdose of feed additives 2. Acute toxicity : Cats most susceptible >horses> cattle/sheep> swine> birds

Question 40

arsenic clinical signs trivalent

Answer 40

``` Clinical signs to trivalent form 1. Acute a. Vomiting/ abdominal pain b. Weakness, staggering ataxia, recumbency c. Weak, signs of shock d. Diarrhea e. rumen/ gastrointestinal atony 2. Subacute a. Watery diarrhea b. Beginning stages of kidney disease; oliguria, proteinuria, polyuria c. dehydration, acidosis, azotemia ```

Question 41

arsenic clinical signs pentavalent

Answer 41

Clinical signs to pentavalent form a. ataxia , torticollis, blindness, ‘sitting dog posture’, normal appetite

Question 42

arsenic lab and lesions

Answer 42

Lesions/ lab findings a. GI irritation, pale swollen kidneys, pale liver b. Consistent with kidney diseas

Question 43

arsenic treatment

Answer 43

Treatment/ prognosis a. Early intervention: GI detox, supportive therapy b. Dimercaprol - antidote for arsenic but only effective if given prior to clinical signs c. Thiotic acid- more effective in cattle but not approved for food animals d. MSMA (mesodimercaptosuccinic acid) and DMSA (dimercaptosuccinic acid); not well tested in US e. Prognosis- inorganic (high mortality rate); organic ( high morbidity)

Question 44

Copper i. Mostly seen in sheep ii. Sources

Answer 44

feed additives, soil/ plant, plants fertilized with used poultry or swine manure

Question 45

copper mechanism of damage

Answer 45

iii. Mechanism of damage 1. Accumulation in hepatic mitochondria and lysosomes 2. Acute hemolytic crisis- excess copper oxidizes erythrocyte membranes, increasing fragility and hemolysis 3. Excess copper causes oxidation of hemoglobin, which forms methemoglobin (does not transport oxygen)

Question 46

copper toxicity mechs

Answer 46

iii. Toxicity 1. Accumulation in ruminants associated with a. molybdenum deficiency- molybdenum binds with copper and complex is excreted by kidney b. lack of sulfate- sulfate reduced to sulfides with bind copper leading to reduced absorption of copper 2. 2-10 week exposure typical in sheep

Question 47

copper diagnosis

Answer 47

Diagnosis 1. See signs of hemolytic crisis 2. Lesions a. Gunmetal kidneys-bluish black kidneys b. Icterus c. Microscopic lesion consistent with hepatic disease and hemolysis d. Copper accumulation in hepatic cells seen with special stain (rubeanic acid) vi. Lab findings 1. Hemoglobinuria, hemoglobinemia, hyperbilrubinemia; elevated hepatic enzymes 2. Serum/whole blood copper levels 3. Liver/kidney copper levels 4. Differentials (Leptospirosis, bacillary hemoglobinuria, babesiosis, anaplasmosis, Onions, Brassica, red maple (Acer rubrum), Phenothiazine anthelmintic toxicoses)

Question 48

copper treatment

Answer 48

vi. Treatment 1. Ammonium tetrathiomolybdate: aids in binding and excretion 2. D-penicillamine: effective but expensive and not approved in food animals 3. In less acute cases: spray molybdenized copper on pasture viii. vii. Mortality/morbidity 1. Mortality high, easier to prevent ix. Prevention 1. Feed with proper copper:molybdenum ratio (6:1)

Question 49

copper accumulation dogs mech

Answer 49

Chronic hepatic copper accumulation in dogs 1. Etiology a. Inherited autosomal recessive trait, appears at 2-6 years old b. Most common in Bedlington terriers, but also see in West Highland Terriers, Doberman pinschers and rarely in other breeds i. Mechanism 1. 1. Copper accumulates in hepatic lysosomes until it exceeds capacity Lysosomes then release copper to cytoplasm causing necrosis and inflammation

Question 50

copper accum clin and tx

Answer 50

Clinical signs 1. Consistent with hepatic disease; occasionally hemolytic crisis 2. Lesions consistent with degree of liver disease xii. Lab findings 1. Elevated liver enzymes, Liver biopsy xiii. Treatment 1. Ongoing chelation therapy with D-penicillamine 2. Corticosteroids, ascorbic acid 3. Limit copper intake

Question 51

Chromium sources and signs

Answer 51

Chromium i. Trivalent form is an essential nutrient; hexavalent form is toxic ii. Sources: paints, tanning, preservatives iii. Clinica signs: dermatitis, nasal irritation, acute GI

Question 52

lead sources

Answer 52

Lead i. Sources: batteries, drapery weights, fishing sinkers, buckshot, plumbing solder, paints, primers, older caulk, farm machinery, automotive supplies, Industry supplies, pesticides ii. Exposure: ingestion 1. Most cases are subacute: ingestion over several days, or lead object in GI tract leaches 2. Lead accumulates in soft tissue and bone; crosses placenta and accumulates in fetal CNS iii. Toxicologic mechanism not fully understood

Question 53

lead diagnosis

Answer 53

Diagnosis lead 1. Clinical signs a. Encephalopathy: seizures, tremors, blindness, depression b. Anorexia, colic, elevated blood lead level c. Anemia, proteinuria d. Neuro, GI, hematopoietic

Question 54

lead tx

Answer 54

Treatment lead 1. Chelation a. Calcium disodium EDTA b. Not approved for vet use, but FDA allows i. Treatment can be toxic 2. Dimercaptosuccinic acid (DMSA) for pet birds 3. D-Penicillamine 4. Supplemental therapy- Thiamine, corticosteroids, zinc, diazepam 5. GI decontamination 6. Surgery, to remove objects

Question 55

lead public health

Answer 55

Public health concerns lead 1. May also be exposure to humans 2. Food animals store lead in bone…meat products should not have bone/bone meal 3. Milk may have traces of lead 4. Contact authorities for herd outbreaks

Question 56

mercury sources

Answer 56

Mercury i. Exposure: rare; inhalational (vapor) or ingestion 1. Sources: thermometer, preservatives, fungicides, anti-mildew paints 2. Inorganic forms accumulate in renal cortex; organic accumulates in brain; both cross placental barrier ii. Clinical signs: varied depending on form and chronicity. Derm, neuro, GI, kidney.

Question 57

iron sources

Answer 57

Iron sources i. Sources: Preparations for oral supplementation, ferrous fumarate, ferrous sulfate, ferrous phosphate, ferrous carbonate, Injectable preparations, Ferric ammonium citrate; iron-dextran complexes ii. Exposure: Accidental oral ingestion most common

Question 58

Mechanism of toxicity iron

Answer 58

Mechanism of toxicity iron 1. Normal: a. ferric iron bound to transferrin and transported through body, Iron needed for oxygen transport by hemoglobin and myoglobin, Excess iron stored as hemosiderin or ferritin 2. Overdose a. Excessive dose overwhelms transferring system leading to excess circulating iron, Unbound iron corrosive and strong oxidant direct damage to epithelial cells, Mitochondrial damage causes hepatic necrosis, Increased capillary permeability and vascular dilatation can lead to cardiovascular collapse iv. Toxicity 1. Dose dependent- Injectable more toxic than oral preparations 2. Oral prep levels (Moderately toxic: 20-60 mg/kg BW, Severely toxic: >60 mg/kg BW, Lethal: >200 mg/kg BW)

Question 59

iron dx

Answer 59

Diagnosis iron 1. Clinical signs a. Oral preps i. Early signs depression, vomiting, hemorrhagic diarrhea ii. May see improvement, followed by hepatic failure, shock, +/- hemolytic anemia 2. Injectable preps a. Two syndromes i. Excessive circulating iron causes depression, shock, acidosis ii. Peracute anaphylactic like reaction, very soon after injection. Likely due to histamine release

Question 60

iron lesions and lab

Answer 60

Lesions iron 1. Oral preps: Mucosa necrosis, ulceration, enteritis, +/- hemorrhage, Congestion of splanchnic vessels, liver,kidney, liver necrosis 2. Injectable preps: edema at injection site, yellowish discoloration to tissues and draining lymph nodes vii. Lab findings 1. Elevated serum iron levels, 50-100% above normal range 2. Acidosis; elevated liver enzymes, hemoglobinuria 3. Iron concentrations in liver difficult to interpret

Question 61

iron tx

Answer 61

Treatment iron 1. GI decon if ingested in last 4 hours BUT activated charcoal NOT effective 2. Milk of magnesia will precipitate iron in GI tract 3. Supportive care 4. Chelation a. Deferoxamine ( Dosage extrapolated from humans; given rapidly can cause cardiac arrhythmias or histamine release) b. Urine will be brown colored at beginning of treatment due to increased excretion of iron c. Oral ascorbic acid given concurrently with deferoxamine enhances excretion d. Serum iron levels should be monitored daily until normal range reached e. Individual animals may have permanent intestinal scarring or liver damage

Question 62

o. Selenium | i. Sources

Answer 62

o. Selenium i. Sources: plants, feed supplements, industrial,seafood ii. Exposure: cattle, sheep, horses—grazing 1. Swine/poultry: grain 2. ii. Waterfowl: irrigation of crops causes leaching of selenium into water iii. Acute, subacute and chronic-> derm, neuro, GI iv. Treatment: acetylcysteine in acute/subacute; copper, arsenics, sulfur-containing proteins

Question 63

mercury tx

Answer 63

iii. Treatment 1. Mercuric salts: egg white, activated charcoal, sodium thiosulfate; sorbitol or saline cathartic, DMSA 2. Alkyl mercurials: when signs apparent, significant damage done. Selenium and vitamin E somewhat protective iv. Public health: alkyl mercurials accumulate in edible organs and muscle—DON’T EAT

Question 64

zinc sources, clinical

Answer 64

Zinc i. Sources: alloys, galvanized coatings, automotive parts, batteries, fungicides, pennies ii. Clinical Signs 1. Dogs: GI-> lethargy-> anemia, hemoglobinuria, icterus 2. Livestock: GI-> decreased weight gain, milk production-> moderate anemia, icterus 3. Most species: hemolytic anemia

Question 65

``` Herbicides: General info Phenoxy herbicides (2,4-D, MCPA, silvex) ```

Answer 65

Herbicides: General info 1. Sources: agriculture, commercial use in lawns, industrial sites, road crews 2. Few herbicides are considered hazardous to livestock at recommended conditions of use 3. Do not generally persist in soil 4. Residues can result from: misuse, urban runoff 5. Consumption of concentrated or mixed herbicide can rarely occur in cattle and dogs 6. Grazing freshly sprayed pastures or eating treated hay 7. No evidence of residues in meat, milk, eggs 8. Phenoxy herbicides (2,4-D, MCPA, silvex)

Question 66

herbicides exposures

Answer 66

Exposures 1. Dogs with access to freshly sprayed lawns 2. Cattle that drink concentrates or tank mixes 3. Potentiate toxic effects of plants

Question 67

herbicides toxicity

Answer 67

Toxicity 1. Absorption from stomach/intestines; not as much dermal 2. See acute more than chronic. Dogs and cattle can tolerate daily doses with little adverse effect

Question 68

herbicide dx

Answer 68

Diagnosis 1. Signs: a. Cattle: anorexia, rumen atony, diarrhea, mucosal ulceration, bloat, depression, muscle weakness b. Swine: vomiting, diarrhea, salivation, tremors, ataxia, weakness c. Dogs: vomiting, diarrhea, bloody feces, ataxia, weakness, clonic spasms Lab a. Chemistry consistent with liver, kidney, muscle damage b. Chemical analysis of forage, urine, renal

Question 69

herbicide tx and public helath

Answer 69

Treatment a. Detox: bath, activated charcoal b. Supportive:No Specific antidotes v. Public health 1. Applicators, farm workers greatest risk. Some evidence of increased incidence of Non-Hodgkins lymphoma in humans 2. Residues in animal products- Not a problem

Question 70

``` Dipyridyl herbicides (Paraquat, diquat) sources and toxicity ```

Answer 70

Dipyridyl herbicides (Paraquat, diquat) i. Sources: Concentrated form for ag use and dilute for home lawn; Applied foliage as contact herbicide to kill vegetation ii. Toxicity 1. Absorption is limited 2. Concentrates in lung 10x higher than other tissues 3. Oral, dermal 4. Chronic toxicity is hazard causes anorexia, respiratory distress, pulmonary lesions, death 5. Clay soils limit availability due to binding

Question 71

``` Dipyridyl herbicides (Paraquat, diquat) diagnosis and lab ```

Answer 71

Diagnosis 1. Acute: vomiting/depression; high doses: ataxia, dyspnea, seizures a. Respiratory signs in 2-7 days b. Subacute or chronic: progressive pulmonary fibrosis iv. Lab 1. Radiographic lung changes 2. Analysis of urine, source product

Question 72

``` Dipyridyl herbicides (Paraquat, diquat) tx ```

Answer 72

Treatment 1. Detox 2. Emetics if noted early 3. Bentonite or Fuller’s Earth: clay to bind herbicide 4. Activated charcoal 5. Clay based kitty litter in emergency but efficacious uncertain 6. Saline cathartic vi. Supportive therapy 1. Assisted ventilation. NO OXYGEN—exacerbate oxidative damage to lung 2. Monitor renal function No specific antidote a. Biochemical antagonists (Superoxide dismutase, Acetylcysteine, Niacin/riboflavin, Ascorbic acid) vii. Prognosis: guarded to grave viii. Public health: residues in animal products not likely

Question 73

Selected herbicides toxic to ruminants

Answer 73

i. Acetemides (propachlor) relatively toxic, anorexia, depression, green undigested rumen contents ii. Benzoic acids (chloramben) low doses: weight loss/anorexia. High doses: bloat, diarrhea, hydropericardium, ascites, enlarged spleen iii. Carbamates (chloropropham) anorexia, salivation prominent; deaths occur; pulmonary, hepatic, renal, intestinal congestion iv. Dinitroanilines (benefin) anorexia, weight loss, bloat, tachypnea. Congested, enlarged lymph nodes, liver v. Diphenyl esters (nitrofen) anorexia, depression, hematuria vi. Nitriles (dichlobenil) anorexia, weight loss; lymphatic, intramuscular hemorrhages vii. Organoarsenicals (Methyl-arsonic acid-MSMA) acute, severe gastroenteritis, watery/hemorrhagic diarrhea viii. Phthalamic acids (naptalam) congestion of liver, kidneys, intestine ix. Thiocarbamates (EPTC, Triallate) anticholinesterase activity x. Triazines (atrazine, simazine) toxic to ruminants; CNS stimulation; enlarged, friable liver

Question 74

Fungicides general, signs, tx

Answer 74

Fungicides 1. Used to treat plants, soil 2. Low toxicity in general so toxicoses is due to flagrant misuse, accidents, carelessness; little info on farm animals and pets 3. Nonspecific signs- anorexia, depression, weakness, diarrhea 4. Analysis of source product more effective than analysis of animal tissues ii. Treatment: 1. Detox & supportive therapy 2. NO specific antidotes

Question 75

Pentachlorophenol wood preservative toxicity

Answer 75

Pentachlorophenol 1. Available on limited basis as fungicide, herbicide, bactericide, wood preservative until 1980s EPA severely restricted its use 2. Structural wood preservative; some still available 3. Livestock could be exposed to freshly treated wood iv. Toxicity: 1. Readily taken up by intestinal tract, skin, lungs 2. See acute and subacute toxicity; not as much as chronic 3. Direct irritant to skin and respiratory tract 4. Neurotoxic effects

Question 76

Pentachlorophenol | clinical signs, lab, tx

Answer 76

Clinical signs: 1. Restlessness, fever, hypertension, weakness, seizures 2. ii. Newborn pigs in contact with wood floor develop hyperthermia, dermal irritation, weakness and die within hours of birth vi. Lab: analysis of blood/urine vii. g. Treatment: 1. Detox: emesis, lavage, activated charcoal 2. Supportive therapy: for hyperthermia, dehydration 3. NO specific antidote

Question 77

Rodenticides General info types

Answer 77

Rodenticides General info a. Third most common source of toxicant exposure in dogs. Rare in cats or farm animals 2. B. Anticoagulants a. Source: baits b. Coumarin derivative: warfarin, brodifacoum, bromadiolone, difenacoum c. Indanedione derivative: pindone, chlorophacinone, diphacinone d. First generation and second generation. Most current anticoagulant rodenticides are second generation i. Brodifacoum most common ii. Warfarin now rare

Question 78

rodenticides exposure, toxicity

Answer 78

Exposure a. Most common in pets, livestock, wildlife with access b. Secondary toxicosis rare 4. Toxicity a. Rate of absorption high b. Inhibit vitamin K epoxide reductase c. Ruminants less susceptible than monogastric animals

Question 79

rodenticides dx tx

Answer 79

Diagnosis a. Signs: consistent with coagulopathy. hemorrhages, hematuria, anemia b. Lab: increased ACT, PT, PTT 6. Treatment a. Detox within 8 hrs b. Supportive i. Blood transfusion c. Vitamin K 7. Prognosis: good if hemorrhage is minimal and controlled. 8. Public health: residues in food animals minimal

Question 80

Cholecalciferol (Vitamin D3) | sources

Answer 80

Cholecalciferol (Vitamin D3) 1. Sources: baits, vitamin supplements, feed additives a. Exposure: b. Baits c. Excessive vitamin D in feed: most common source in food animals d. Excessive use as growth promoter in large breed dogs

Question 81

Cholecalciferol (Vitamin D3) | toxicity, dx

Answer 81

c. Toxicity a. Vitamin D promotes calcium retention b. Hypercalcemia causes cardiac dysfunction and necrosis of renal tubules c. Acute and chronic toxicity seen 3. d. Diagnosis a. Clinical signs: 12-36 hrs after ingestion i. Vague early signs progressing to renal failure, and cardiac signs b. Lab: serum calcium level >2mg/dl i. Elevated serum phosphorus c. Increased kidney enzymes

Question 82

Cholecalciferol (Vitamin D3) | tx

Answer 82

e. Treatment a. Detox: emesis, activated charcoal b. Supportive care: for kidney failure c. Corticosteroids reduces intestinal absorption and calcium excretion d. Salmon calcitonin: reduce calcium levels 5. Prognosis: guarded

Question 83

Phosphides (zinc, aluminum, calcium) | sources, toxicity

Answer 83

Phosphides (zinc, aluminum, calcium) 1. Sources: rodenticides, grain fumigants a. Exposure: ingestion of baits mainly dogs, Phosphine gas 2. Toxicity a. Acute toxicity in dogs b. Subacute and chronic not described

Question 84

Phosphides (zinc, aluminum, calcium) | dx

Answer 84

Diagnosis a. Clinical signs: vomiting, tremors, weakness, seizures b. Rarely see colic in horses and bloat in cattle 4. Lab: analysis of stomach contents…not consistent a. Stomach contents have acetylene, “dead fish” in odor

Question 85

Phosphides (zinc, aluminum, calcium) | tx and ph

Answer 85

5. Treatment a. Detox b. Supportive: bicarb to combat acidosis 6. Public health: vomitus can give off phosphine gas…hazard to animal care workers

Question 86

Strychnine exposure toxicity

Answer 86

Strychnine 1. Source Baits for gophers and squirrels a. Treated seeds Exposure: Used in malicious poisoning of dogs, Ingestion of baits, DOES cause secondary toxicoses, esp. in raptors. Due to persistence in food and environment 2. Toxicity a. Causes acute toxicity only b. Dogs more susceptible than cats c. Large animals very sensitive d. Poultry resistant

Question 87

strychnine dx

Answer 87

Diagnosis a. Clinical signs i. Acute onset of tonic to titanic seizures, hypersensitivity ii. Advanced signs: sawhorse stance, hyperthermia 4. Lab: strychnine in urine, stomach contents, liver

Question 88

strychnine | tx

Answer 88

``` Treatment a. Detox: lavage, activated charcoal, fluids to encourage excretion b. Supportive: anti seizure meds, muscle relaxants c. NO ketamine or morphine d. Warm, calm, dark environment e. NO specific antidote 6. Prognosis: good if treated promptly ```

Question 89

``` Bromethalin source toxicity dx lab tx ```

Answer 89

Bromethalin 1. Source: baits a. Exposure: ingestion of baits…cats and dogs 2. Toxicity a. Rapidly absorbed from GI tract b. Acute and chronic toxicity seen 3. Diagnosis a. Signs: varied and dose dependent i. Acute: tremors, hyperexcitability, hyperesthesia, fever ii. Subacute: ataxia, neurologic, vomiting 4. Lab: EEG shows abnormalities; inconsistent results from chemical analysis of bromethalin in stomach contents 5. Treatment a. Detox: emetics, activated charcoal, saline cathartic b. Supportive: cerebral edema, fluids, seizure management c. NO specific antidotes

Question 90

Yellow Phosphorus

Answer 90

Yellow Phosphorus 1. glows in the dark:” when exposed to moisture, emits greenish light a. rare use as rodenticide b. Exposure: ingestion Toxicity: a. Absorbed from GI, respiratory, damaged epithelium b. HIGHLY toxic 3. Diagnosis a. Signs: early signs are violent vomiting and diarrhea with recovery in 24-48 hrs. Breath has “garlic odor” i. Relapse into depression, severe shock, hepatic failure, death b. Lab: consistent with hepatic failure