CIH Toxicology

Aliphatic hydrocarbons

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Reproductive Hazards

2 ethoxyehtanal acetate ethylene glycol monoethyl ether acetate. readily absorbed through the skin.(major route.)

carbaryl

A carbamate derivative and also a cholinterase inhibitor.

Procarcinogen

A chemical agent which does not cause cancer on its own but when metabolized doe cause cancer. A procarcinogen is a chemical that must be metabolized to the direct-acting carcinogen. The direct-acting carcinogen then goes on to produce cancer.

Parathion

A cholinterase inhibitor. a test for cholinterase test will help to determine exposure to parathion. common route of entry is the skin. agriculture workers are the most commonly affected group.

Cocarcinogen

A cocarcinogen increases the carcinogenic effect of a chemical when it is given along with a carcinogen. classic case PAH and croton oil.

Tolerance

A condition of decreased responsiveness to a toxic chemical as a result of prior exposure to the chemical. may be due to either less chemical reaching the site of action or reduced responsiveness of the tissue to cause damage.

Siderosis

A condition resulting from exposure to welding fumes that is characterized by accumulation of metal oxides in the lung without apparent physical symptoms. A pigmentation of the lung due to iron oxide exposure. some patients have chronic bronchitis and dyspenea. differential diagnosis is difficult.

Antimony

A constituent of printers type. semi-conductor industry as a dopant symptoms are similar to arsenic poisoning. trivalent salts of antimony are much more toxic than prevalent derivatives.

Talc

A form of silicate can cause nodular fibrosis when contaminated with silica or asbestos.

Methyl ethyl ketone (MEK)

A pungent solvent with a high vapor pressure. causes narcosis and is also capable of defatting the skin resulting in cracking and eventually dermatitis.+

Silver

Accumulation in the skin, cornea, conjunctiva and lens lead to argyria. skin turns grayish blue especially over exposed area. pigment in the eye can cause problems with light adaptation. silver compounds have a low TLV .01mg/m^3 because it is held tightly by the body.

Carbon Tetrachloride

Acute effects: Central Nervous system. excitability, dizziness, narcosis. Chronic Effects: Liver damage.

Exposures

Acute: Exposures over a short period of time (minutes to hours) Subacute Exposure: exposure less than a month. Subchronic: Exposures over medium duration (days to weeks or months) Chronic: exposures over a long period of time (years)

Effects

Acute: Immediate effect from exposure. Chronic: effect only noticed after long exposure. Latency period: Amount of time between first exposure and onset of disease.

Afebrile

Afebrile without fever. ex: nitrogen dioxide. Febrile diseases: metal fumes, teflon, flax.

Primary Irritant

Ammonium (NH4), HCL,Sulfuric acid ( H2S04), Chromates.

Causes a benign simple pneumoconiosis with an abnormal CXR and normal PFT

Amorphous silica, Barium, Tin Oxide.

Promotor

An agent that increases the carcinogenic response when it is applied after the carcinogen. Phorbol esters are the most well known promotors. phorbol esters can also act as cocarcinogens.

Copper

An essential nutrient. enzymes such as the peroxides, catalase and cytochrome oxidase require copper. excess copper is stored in the liver and bone marrow.

Chemical Asphyxiant

Aniline, sodium nitrite, hydrogen cyanide.

Hepatotoxic (Liver

Apoptosis: cellular suicide. Necrosis: inflamed cell death. fatty liver: increased hepatic lipid content. cirrhosis/fibrosis-replacement functioning hepatocytes with fibrotic tissues. common hepatotoxins: CCL4, halothane, TNT, methylene dianiline (MDA), vinyl chloride-liver cancer, ethanol, acetominophen. `

Simple asphyxiant

Argon, nitrogen, carbon dioxide, methane (CH4)

Obstructive type lung impairment

Asthma, chronic bronchitis, emphysema (all produce restrictions/obstructions in the bronchioles. forced vital capacity (FVC), Forced expiratory volume in 1 second. ) FEV FEV- measures the ability to force air out of the lungs quickly. Below normal for patients because lungs have less ability to deflate quickly.

Bladder Carcinogens

Benzidine (confirmed occupational human carcinogen) magenta. 4-aminobiphenyl. aniline-based dyes (not analine alone) beta-naphthylamine, potent bladder cancer.

Enzymes

Biochemical (frequently a protein) that speeds up a biochemical action. enable metabolism, but not consumed in the process. CYP P450 system in liver generally "detoxifies" substances. Substance more easily excreted through kidneys (urine) or liver (bile).

Neoplastic conversion

Biotransformation of a chemical. ' interaction of the ultimate carcinogen with cellular component. fixation of the carcinogenic damage. multiplication of altered cells.

Skin Irritant

Can damage the skin by: altering the Ph of the skin, reacting with skin proteins, removing protective lipids from the skin surface. PH over 11, presents a significant risk to skin. Low ph (acidic solutions) are tolerated better by the skin.

Carcinogens

Cause cancer: All carcinogens are mutagenic. examples; benzene, cadmium, cigarette smoke, asbestos, vinyl chloride, radon, chromium, arsenic, soots, mineral oils, wood dust, nickel compounds, beryllium.

TNT

Causes Dermatitis

Bagasse

Causes pulmonary fibrosis rather than simple pneumoconiosis.

Antagonistic:

Chemicals interfere with effects of each other. Example: alcohols preferentially metabolized over methanol. Atropine and organophosphates.

Organophosphate Pesticides

Chest tightness. abdominal cramps. increased salivation.

Chromium

Chromium occurs in several valence states from a toxicological point of view the 2 most important states of chromium are 3 and 6. trivalent and hexavalent Cr3 URT and skin irritant. Cr+6 cause dermatitis, classic ulcers. A1 carcinogens chromium salts, production of occupational asthma.

Arsenic or arsenicals

Chronic exposure results in malaise, fatigue and possible peripheral neuropathy and GI disturbances. a classic sign of intoxication is nasal sputum ulceratin, pale bands on fingernails, anemia, A1 known human carcinogen.

Fluorides

Chronic exposure: anorexia, nausea, osteosclerosis. acute exposure-ulcers of the skin.

Acute Beryllium poisoning

Contact dermatitis mild respiratory inflammation. pneumonities with pulmonary edema. 3 types of disease, dermatitis, ulcerations granulomas

Aromatic Hydrcarbons

Contain benzene ring. polycylic aromatic hydrocarbons (PAH) or Polynuclear aromatics (PNA) contain 2 or more benzene rings. health effects: CNS, hepatotoxin, renal effects, bone marrow, blood forming systems. many are carcenogenic.

Pesticides

DDT-chlorinated hydrocarbon pesticide not highly toxic. Methoxychlor- pesticide of moderate toxicity.

Adduct

DNA adducts are results of xenobiotics interacting covalently with DNA. when a chemical bonds to DNA it becomes damaged. This would be part of a mutation. in scientific experiments, DNA adducts are used as bio-markers and are themselves measured to reflect the amount of cancer in animals.

Immunotoxins

Damage to the immune system. innate immunity is present at birth. adaptive immunity is a reaction to antigens. examples: benzene, perchlorate, anti-neoplastic drugs, ionizing radiation, ethylene oxide.

Carcinogenic Effect

Early development of tumors. increase in benign tumors, greater multiplicity of tumors. characteristic of carcinogensis as a toxic effect; persistence, cummulative effect, developed onset.

In vivo

Experiments conducted within living bodies.

In Vitro

Experiments or studies conducted outside living bodies. Within a glass or test tube. artificial environments.

Skin Cancer

Exposure to aresnic trioxide. coal derivatives. previous exposure to sunlight.

Trichlorethylene

Exposure to these vapors followed by ingestion of alcohols lead to severe flushing reaction known as degreaser' flush. blocks the normal catabolism of alcohol, resulting in the accumulation of acetaldehyde which is believed to cause flushing.

Passive Transport

Filtration is a form of passive transport. involves the flow of small solutes through pores with bulk water flow. since no energy is used it is a form of passive transport. lipid solubility major determination ofnrate of transfer usually measured by octonal/water partition coefficient.

methemoglobin

Found when the iron in the heme is oxidized from the +2 valence state to the +3 valence state. amine and nitro containing molecules are good methemoglobin formers. methylene blue is given to convert the methemoglobin back to hemoglobin again.

Chemical Idiosyncrasy

Genetically determined abnormal susceptibility to a chemical. patients exhibiting an atypical reaction to a chemical due to a genotoxic disorder such as missing an enzyme are said to have an idiosyncratic reaction.

Secondary Irritant

H2S, Ketones, esters, alohols, and ethers.

Ethylene oxide

Heavy industry- solvents, detergents, antifreeze. sterilizer in healthcare and other industries. volatile explosive and reactive. Health effects: hepatotoxin, nephrotoxin, neurotoxin. carcinogen causing leukemia. linked to miscarriages.

Paraquat

Herbicide used to control marijuan growth. causes renal failure followed by acute alveolitis and rapid pulmonary fibrosis when ingested.

Mechanisms Continued 2

Impaction Sedimentation. Diffusion.

Active Transport

Important for excretion. the chemical can move against the concentration gradient. very important for the elimination of foreign compounds. cerebrospinal fluid, kidney has at least 2,2and 4 active transport systems respectively. requires energy for its selective saturable transport (carrier) system.

Terata

Include both structural i.e gross skeletal and visceral malformations and functional alterations although many authors use it as a synonym for malformations.

Mechanisms

Interference with enzymes. uncoupling of biochemical reactions. inhibition of oxygen transfer (cellular). blockade of hemoglobin oxygen transport. synthesis of toxic metabolite.

Nitrogen Dioxide

Irritant gas that would most likely irritate the lower regions of the respiratory tract. pulmonary edema, reduced olfactory sense.

TDI

Known for ability to cause sensitization at very low levels of exposure. once an individual is sensitized, subsequent exposures to very low levels may cause a severe asthmatic attack. Irritation of skin, eyes and respiratory tract.

Skin Exposures

Lipid soluble (dissolved in fat) are absorbed more quickly than water soluble substances. nonpolar substances are readily absorbed.

Nickel Compounds

Lung cancer. adult respiratory distress syndrome(ARDS) contact dermatitis. metallic nickel-contact dermatitis and airway irritation, nickel carbonyl gas exposure can produce fulminant pneumonitis, encephalopathy and ARDS. Large effects of nickel inhalation include cancers of the nose, nasal sinuses and lungs. % of eczema cases.

Cotton Dust 2

May contain many substances. mold, bateria, soil, pesticides. Health effects: difficulty breathing. tightness in chest. noticeable on the first day back to work after a few days off. byssinosis (brown lung disease) increased risk of emphysema, bronchitis.

Manometer

Measures stack velocities and exhaust volumes.

Heavy Metal Toxins

Mercury, silver, bismuth, defined as atomic wights > or densities >

nitroglycerin

Monday morning angina with exposure to nitroglycerin. after prolonged exposure, anginal pain may appear at the end of the weekend or vacations. may have cardiotoxic effects. used to treat some forms of heart conditions.

Threshold Values

NOEL:No observable effect level. NOAEL: No observable adverse effect level. LOEL: Lowest observable adverse effect leve. LOAEL: Lowest observable adverse effect level.

Polychlorinated Bipheyls (PCBs)

Neurobehavioral developmental delays. infants may be exposed to breast milk secondary to high concentrations of pcbs in maternal milk. chloracne most common result of exposure to pcb.

Neurotoxins

Neuropathy (death of nerve cells): organic and elemental Hg, trimethytin, AL, Mn, Methanol. Axonopathy (damage to axons): acrylamide, n-hexane, carbon disulfide, organophosphate insecticides. Myelinopathy (damage to myelin) Triethylin, hexachlorphene, lead. Peripheral neuropathy (mercury, arsenic, thallium).methyl n-butyl ketone, alcohol, acrylamide. Organic metals are way more toxic than inorganic metals

Neurotoxins Continued

Neurotransmission Toxicity (interrupt signal): Blocking agents (block acetycholline e.g atropine). De-polarizing agents (DDT). Stimulants (caffeine, nicotine, cocaine.) Depressants (aromatic solvents, VOCs, alcohols.) Anti-cholinterase agents (organophosphates and carbamate pesticides)

Pneumoconioses continued

Non proliferative (non-progressive, simple)-after exposure stops the disease stops. talc: talcosis, tin ore (cassiterite): stannosis, iron oxide: siderosis. Biological pneumoconiosis: cotton dust: byssinosis, moldy sugarcane: baggassosis, gum of acacia (or arabic) printers asthma.

Arsine gas

Notorious for its ability to cause massive destruction of red blood cell hemolysis at very low concentrations. IDLH is 6ppm odor threshold 1-2ppm. TLV 0.05ppm

Metals

Organic metals generally more toxic than inorganic metals (methylmercury, tetraethyl lead. ) metals not easily excreted are more toxic (lead, arsenic) Chelation: binding of metals for excretion. also binds essential metals.

Organogenesis

Period of development of conception when the organs are forming. Most critical and sensitive time in development. In studying lab animals is the period of greatest susceptibility to teratogenic agents.

Skin Disorders Continued

Photosenitization: photoactive chemical absorbed into skin, sunlight activates chemical. St. Johns wort, horse brushes, tetracycline, anthracne, some dyes, pitch (tar). Urticarial Reactions:Smooth, slightly elevated patches (Wheals) that are redder or paler than surrounding skin.

Pneumoconioses

Pneumoconiosis: dusty lung disease. Proliferative (progressive, complicated.), after exposure stops keeps going, progresses. Silica, silicosis. Asbestos: Asbestosis. Coal: black lung, anthracosis. bauxite (Al ore): shavers diseases.

Ehtylene glycol monomethyl ether

Presents greatest reproductive hazards based on animal studies. glycol ethers, especially the methyl ester of ethylene glycol has been shown to severely depress sperm production in lab test animals.

Phosgene

Primarily a skin, respirator and eye irritant. Mucous membranes, skin,lungs and eyes will suffer irritation from exposure.

Hydrogen sulfide

Primarily as respiratory irritant in low conentrations. mild poisoning- irritation of conjunctiva with photobia. powerful asphyxiant when sulfur combines with organic chemicals at high temperatures. at 150ppm or higher-olfactory nerve paralysis (employees exposed may be unaware)

Toluene Diisocynate (TDI)

Produces allergic symptoms upon inhalation and cause asthma.

Phenol

Readily absorbed through the skin.

Blood testes barrier

Regulates the passage of a variety of substances composed of tight junctions between sertoli cells in the testes. has been shown to affect the rates of passage of a number of substances into the seminiferous tubules.

Aerodynamics

Respirable 4 microns-hazardous when deposited in the gas exchange region. Thoracic-10 microns anywhere in the lung airways and gas exchange region. inhalable: 100 microns anywhere in the respiratory tract.

Tellurium

Rubber, elctronics, glass and ceramics industry. route of exposure: inhalation or ingestion. garlic odor results from metabolism of tellurium to dimethyl telluride. acute exposure: garlicky odor of breath and sweat. blue/black skin discoloration, fatigue. nausea. chronic exposure garlicky odor of breath. metallic taste fatigue dry mouth,

Mechanisms continued2

Sequestration: DDT and PCBs stored in fats. Heavy metals stored in bones. dusts overloading lung capability to remove.

Immunological system

Set of 20 large proteins, help certain immunological reaction. enhances phagocytosis. produces inflammation. directly lyses some organisms.

Metal fume fever

Several metallic oxides are responsible. appears several hours after exposure. occurs commonly in welding and foundrys. most common agent is zinc oxide, produced from welding galvanized steel freshly generated magnesium if inhaled in sufficient quantities.

Acidic environment

Since the lipid soluble (non-ionized) form of a chemical is the species which crosses the membranes and an acidic environment favors formation of this species, weak organic acids transport would be increased. The same would be true for organic bases in the environment.

Phosphorous Comounds

Skin burns, occular irritation, CNS depression, pulmonary edema, elemental phosphorous lead leads to progressive aseptic necrosis of the bone.

Inorganic Arsenic

Smelting operations, battery production, pesticides. exposure routes: inhalation, ingestion. acute exposure may be lethal. chronic health effects: cancers: lung, liver, leukemia, hepatotoxin, nephrotoxin. BEI-Arsenic in urine at the end of the work week.

Dose Response Curves

Steep Curve indicates small variability in response. Shallow curve indicates wide variability in animal response. General Rule: If a chemical has the same degree of toxicity across species, then probably similar toxicity in humans. animals and humans are in the same range of susceptibility when dose is compared on the basis of body surface area.

Toxicokinetics

Study of the movement of toxicants through the body. Pharmacokinetics: the study of drug movement through the body.

Toxicant

Substance that interferes with the normal functions of the body. A toxin is biological in nature (mold, bacteria. etc. toxicant examples: lead, asbestos etc.

Effects (2)

Systemic Toxicity: Adverse effect affecting whole systems within the body. Example: organic solvents affect kidneys and liver. Local Toxicity: Adverse effect affecting solely site of exposure. Example: organic solvents may cause dermatitis.

Cardiovascular system.

Tachydyrshythmias (abnormal heart rate): chlorinated hydrocarbons, aromatic solvents, aliphatic hydrocarbons, halo-fluorocarbons. Cardiomyopathy (damage to heart muscle): lead, arsenic, cobalt, alcohol. carbon monoxide: damage to blood vessels Carbon disulfide.

Cadmium

Target organ in the kidney and lungs smelting, electroplating, soldering, welding. acute exposure may cause pulmonary edema. chronic exposure may cause pulmonary emphysema, lung cancer and kidney problems. BEI-cadmium in blood or urine. suspected human carcinogen.

Benzene 2

Target organ. (bone marrow) (hematopoeitic systems.) causes anemia and leukemia, signs and symptoms include headache dizziness, fatigue loss of appetite, irritabiity, nervousness nosebleed, and other hemorrhagic manifestations.

Dose is important

Teaspoon of a substance can be 10X more hazardous for a young child than for an adult. (body weight and growing body.)

Ionization

The degree of ionization is dependent on Pk and PH

LC50

The lethal concentration for 50% of the exposed organisms in air. it is determined statistically using the proportions of animals killed from several different dose/exposure groups. prohibit analysis is one common method.

Dimethyl Tin

The most toxic CNS. it is rapidly absorbed through intact skin. symptoms are sometimes delayed 3 days from exposure. organotin compounds hav a pel of .1mg/m^3

Genotoxic Toxicology

The study of DNA as the target molecule for toxic effects. 1) determination of the effects of agents on human gene pool i.e impact on future generations, and 2) identification of potential carcinogens through the use of a submamalian or in vitro tests.

Toxicology

The study of poisons, studies how living organisms physically respond to poisons. Xenobiotic: foreign chemical to the body not produced by the body or expected to be there.

Sensitizer

Toluene diisocynate (TDI) and Methylene biss-phenyl isocynate (MDI) skin and respiratory sensitizers.

Vanadium

Upper respiratory tract irritation- when exposed to vanadium dust. coughing wheezing and irritation of the eyes, nose, and throat can occur. heavy exposure-green discoloration of tongue due to oral deposition of vanadium dusts.

Inorganic Carcinogens

Uranium, Potonium, radium, radon gas, nickel, chromium, beryllium.

Beryllium

Very lightweight used as hardening agent. acute exposure can cause pneumonitis, sensitizer to beryllium. Chronic Exposure: berylliosis, scarring of lungs, lung cancer.

Rodenticide

Warafin, red squill, norbromide.

General Rule

Water soluble go directly from the small intestine to the liver via the blood. non-soluble substances tend to be less toxic. chemicals tend to b most toxic through exposure route permitting greatest entry (often lungs).

Fluropolymers

When heated above 325C a mixture of decomposition products have been shown to cause: chills and aches in muscle joints. fever. polymer fever Conditions similar to metal fume fever.

2,3,7,8 TCDD (dioxin)

a contaminant found in trichlorophenoxy-acetic acid. PCBs can be conaminated by dioxin isomers.

TCDD

a specific isomer of dioxin. extremely toxic when tested in animals. human-chloracne a characteristic skin condition. methyoxychlor is a pesticide of moderate toxicity. 7

Potentiating Effects

a substance that normally has no toxic effect becomes toxic in the presence of another substance.

Eopxide

a very reactive, stearically strained molecule that can interact with DNA or other cellular components. The epoxide is hydrated by epoxide hydrase.

hydrofluroic acid

a weak acid which is why it produces such severe and painful burns. it causes damage by penetrating the skin, typing up calcium and killing underlying tissue.

Toxic effects

absorption of the compound exceeds excretion. the compound produces irreversible effects. target organ uptake exceeds clearance.

Trimellitic Anhydriden (TMA)

acts as a hapten, forming antegenic protein complexes with human proteins. develop rhinitis, asthma, hemorrhagic pneumonities, and hemolytic anemia secondary to host immune response to these haptens.

Formaldehyde 2

acute irritant, irritation of the skin, eyes, nose and throat. chronic eczematous dermatitis. affect hands, arms of exposed worker. evidence linked to cancer of the nasal cavities in fisher rats.

Synocarcinogenesis

additive or synergistic effect of 2 carcinogens.

Epoxy Resins

allergic dermatitis. asthma. scleroderma-like syndrome.

Mutagen

alter genetic material. may cause cancer or birth defects in children of either parent. not all mutagens are carcinogenic.

Hydrogen Cyanide (HCN)

an be absorbed through the skin and cause cellular asphyxiation by blocking use of oxygen in the cells.

Vinyl Chloride Exposure

angiosarcoma of the liver. raynouds syndrome acroosteolysis

Warafin

anticoagulants such as warafin are most commonly used in rodenticides.

Inert Dusts

antimony tin barium these metals deposit in the lungs but do not tend to elicit any significant fibrotic reaction but can lead to the formation of pulmonary nodules resulting from collections of dust-filled macrpophages.

Carbon Disulfide

atherosclerosis. peripheral neuropathy. psychosis. cardiac ischemia. potent neurotoxin in one study of chronically exposed humans, 88% of those exposed developed polyneuritis. Experimentally seen in dogs.

Lung Cancer

bis-chloromethylether (BCME) Aresenic. Coal tar pitch volatiles. most potent lung cancers known.

Tetraethyl Lead

can cause acute plumbism and is rapidly abnormal through the skin. symptoms of severe toxicity include delusions, hallucinations, hyperactivity load shouting and laughing. not a potent skin sensitizer. monitored using urine lead levels. wrist drop, lead colic, lead line and basophilic stippling (inorganic lead toxicity) CNS irritability-organic lead toxicity.

Chlorofluorocarbons

cardiac arrythmias. sensitize the heart to epinephrine.

1,3 butadiene

causes cancer in mice. frost bite, dermatitis, eye nose and throat irritation,

Ammonia

causes irritation of the mucous membrane.

Methanol

causes severe occular damage. formaldahyde is thought to be responsible for this effect. methanol is oxidized by the enzyme dehydrogenase to form formaldahyde.

Organochlorines

chlorinated hydrocarbons-DDT, chlordane, aldrin, kepone. stored in body fat. non-polar, lipied soluble. hepatotoxic, nephrotoxic neurotoxic.

Carbon tetrachloride

classic and most studied hepatotoxin. can cause occupationally-related cirrhosis of the liver. injury-less common because used less insolvents, fire extinguishers and cleaning fluids. both hepatotoxin and neurotoxin. probably human carcinogen, centrilobular necrosis of the liver, acute tubular necrosis of the proximal tubes. hepatocellular carcinoma synergistically with ehtanol.

Mercury

classic symptoms include mental changes, stomatitis, and tremors. elemental mercury not absorbed well into the GI tract is readily absorbed in the lungs. 8% absorbed in the alveolia monomatic gas.

Coal tar pitch volatiles

coking, paving, roofing, Al smelting. Aromatic and PAHs Health Effects: lungs, kidneys, bladder, skin. Carcinogenic in lungs kidneys and skin

Nitrogen

considered a simple asphyxiant since it displaces oxygen and reduce oxygen concentrations below 18%.

Cotton Dust

cotton dust may contain many substances-molds, bacteria, soil, pesticides, other. health effects: difficulty breathing, tightness in chest. noticeable on first day back to work after a few days off. byssinossis (brown lung diseases) increased risk of emphysema, bronchitis

Axonopathy

degeneration of the schwann cells. demyelination can occur secondary. degeneration of the axon may follow demyelination.

Skin Disorders

dermatitis; the most prevalent occupational disease accounting for more than 40-45%. occurs in every industry and occupation since skin irritants and sensitizers are used throughout industry. alkalis, expoxies, solvents associated with dermatitis. Contact Dermatitis: Generally found in area of exposure. Occupations: magazine printers, agriculture, artists, automobile, aircraft manufacturing, mechanics.

Descriptive toxicologist

designs and conducts long term toxicity tests in lab animals.

Structural Variations

differ from malformations in that they may not adversely affect survival or death.

Additive Effects

effect two separate chemicals acting independently is additive. Organophosphates malathion and parathion.

Sensitization

enhanced response due to previous exposure.

Organic tin compounds ( Tributyl and dibutyl)

extremely toxic causing skin and mucous membrane burns.

nickel carbonyl

extremely toxic gas that is formed from nickel and carbon monozide. estimated that 30ppm for 20 minutes is lethal in humans. initial symptoms: headache and vomitting. delayed symptoms include acute pneumonitis.

Environmental Toxicologist

focuses on the study of adverse health effects in wildlife ecosystems or in exposed humans exposed to environmental pollutants.

acute poisoning remedies

gastric lavage: insertion of a tube into the stomach. activated charcoal: swallow activated charcoal poweder, adsorbs toxicant. cathartic (saline): increase stool output.

carbon monoxide

headache -most common complaint. patients with coronary disease, angina at lower than usual exercise levels with small exposure. causes a shift in the hemoglobin to oxygen dissociation curve to the left. biological half-life of carboxyhemoglobin-4 hours or 60-90 minutes with 100% oxygen via face mask. cardiac ischemia. methylene chloride (synonym dichlormethane) metabolized to CO2 in paint stripping.

Halogenated Hydrocarbons

health effects: CNS, hepatotoxins, nephrotoxins. chlorinated compounds most common. l4, CH2CL2, (CL2)2, CHCLCCL2. carbon tetrachloride CCL4 potent hepatotoxin. Mythylene chloride CH2CL2, metabolizes into CO

Ethylene Oxice

heavy industry-solvents, detergents, antifreeze. sterilizer in healthcare and other industries. volatile, explosive and reactive. health effects: hepatotoxin, nephrotoxin, neurotoxin. carcinogen causing leukemia. linked to miscarriages.

Nephrotoxins (kidney)

heavy metals: kidney vasoconstriction, block sulfhydryl groups. Halogenated alphatic solvents: carbon tetrachloride GGL4, and chloroform CHCL3 metabolized to COCL2 (phosgene). Cadmium ( a metal) classic for kidney damage. mercury, chromium, uranium.

Cobalt

implicated in asthma and the aggressive fibrosing lung disorder, hard metal disease. associated with cardiomyopathy and was once used as an additive in beer as a foam stabilizer. cobalt salts are readily absorbed from the GI tract. 80% excreted via urine, 15% in feces.

cyanide

inactivates cytochrome a3. this effectively prevents the cell from using oxygen as its electron receptor. Respiration is therefore shutdown even though there is enough oxygen available.

irritation

inflammation, congestion, edema

Stages of cancer

initiation: damage to cellular DNA (most DNA damage is repaired.) Latency period: disease remains dormant. Promotion: tumor cell growth begins. Progression:tumor tissue becomes neoplasm. (abnormal growth.) (neoplasms are normal cells with abnormal growth.

Lead exposure

irritability, acute encephalopathy abnormal spermatogenesis. neuropathy and slowing of motor skills. wrist drop when motor neuropathy is pronounced. 90% found in the bone due to similarities in charge and size lead may replace calcium in the hydroxyapetite lattice structure in the bones by and exchange absorption reaction .

Uranium

is deposited in the bone but exerts its toxic effect on the kidneys.

decaborane

less toxic of the boron

Organochlorine Insecticides (Clordane and lindane)

linked to aplastic anemia and myeloproliferative disorders.

Hexavalent chromium exposure

linked to lung cancer. pulmonary effects of chromium exposure include airway irritation, produtive cough and bronchospasm, lung cancer which is usually sqyamous cell in origin.

coal Tar pitch volatiles

lung cancer, acne folliculitis in workes with bad hygiene habits, phototoxic reactions, allergic dermatitis in animals.

Flu-like symptoms.

magnesium oxide fumes. nascent zinc oxide fume. zinc oxide fume. metal fume fever caused by exposure to freshly generated (nascent) fumes of zinc (primary) and magnesium and their oxides. copper also known to cause metal fume fever.

Solvents

major effect are CNS. lipophillic (fat loving.) seek fatty membrane of nerve. CNS effects increase with length of carbon chain. CNS effects increase with halogenated compounds, especially chorine. unsaturated compounds tend to enhance CNS depression.

Lungs

major route of exposure because they are very efficient at collecting and absorbing toxicants due to tremendous surface area. Excreted through lungs: benzene, carbon tetrachloride, carbon monoxide.

Simple diffusion

major toxicants diffuse through membranes. hydrophilli molecules may use aqueous channels.

Forensic Toxicology

medical/legal aspects of chemical exposure.

Ethylene Oxide Exposure

mixed motor-sensory peripheral neuropathy. nausea and vomiting. toxic encephalopathy. known to cause cancer in female rats and is suspected of causing cancer cancer in humans. it is flammable and presents a severe fire hazard.

Central Nervous System (CNS)

most frequently involved in systemic toxic effects. usually when a substance has an effect on the internal organs, the CNS has already experienced some effect whether it is narcosis or some other impairment.

Organic mercury

most organic mercurials are mainly excreted in the feces (up to 90%) Inorganic mercury compounds are primarily eliminated in the urine.

Alkyl Mecurials

most toxic when ingested.

FEV1/FVC Ratio

most useful in determining if a worker has an abnormal lung function. although FEV1 is a very useful measure, medical personnel get more information from the ratio FEV1/FVC.

Lead

muscular pain associated with inorganic lead toxicity. often associated with joint and muscle pain. irritability muscle pain and loss of appetite associated with both inorganic and organic lead. Corprorphyrin III are elevated in the urine. used a diagnostic testing. damages the hematopoeitic system through the system through inhibition of the heme synthesis, shortened rbc life and stimulation of the erythropoeitic system.

Cause pulmonary Edema

nickel carbonyl. phosgene nitrogen dioxide.

Facilitated distribution

no energy is expended. the substrate is not moved against a concentration gradient.

Pentaborane

noted for its ability to cause CNS effects at very low concentrations. can also cause liver and kidney damage. most toxic hydride of boron.

Aliphatic Hydrocarbons

open chain C1-16 GasesC1-4 Liquid C5-16 SolidsC16 and higher

Asbestos 2

open faced cassette sampling. commercial grade talc tends to be heavily contaminated with asbestos and sometimes silica. 6 types of fiber-serpentine group chrysotile (white asbestos). amphibole-amosite (brown asbestos) crocidolite (blue), tremolite anthophylite, actinolite, most common commercially used. crysotile, amosite and crocidolite. amphibolegroup most potent inducers of malignant mesothelioma. crocidolite-most potent carcinogen. mesothelioma-fatal tpe of caner

Organophosphates

parathion, malathion. interferes with cholinterase. causes erratic signals from nerve endings. symptoms: twitching, weakness, tremors. may be reversible if treated quickly.

Diborane

potent lung irritant

formaldehyde.

preservative in medical labs, found in building materials, used as fumigant. exposure routes: inhalation, skin absorption. health effects: sensitizing agent can immune system. nasal and lung carcinogen, lethal when swallowed. dermatitis.

colophony

produced when pine resin flux is used in soldering. occupational asthma.

Asbestosis

produces a diffuse interstitial fibrosis.

dealkylation

removal of a an alkyl group from sulfur, nitrogen or oxygen.

Mechanisms continued

removal of metallic co-factors (chelating). interfere with general cellular functions. immunosuppression or hypersensitization. chemical irritation of tissues. direct cellular toxicity.

Toxicity

route of exposure, duration of exposure, and frequency all directly affect the toxicity of a chemical in a given exposure situation.

Gauley Bridge Tunnel

several hundreds of deaths attributed to exposure to high concentrations of silica dust.

Benzene

simplest aromatic hydrocarbon. exposure routes: inhalation, skin absorption. metabolized in several steps- 60% becomes phenol. carcinogen-leukemia BEI- s=phenylmercapturic acid in urine end of shift. t,t-Muconic acid in urine end of shift.

Dose of moderately toxic chemical to produce death

slightly toxic agent produces death in a range of 5-15g/kg. very toxic 50-500mg/kg. extremely toxic 5-50mg/kg.

Hapten

smaller molecular weight compounds that react with proteins in the body to produce a substance that is antigenic ie. substance of inducing human response.

Inorganic Lead

smelters, battery production, firing ranges, lead paint removal, welding. organic lead is a neurotoxin. chronic exposures affect nervous system, decrease sperm count, accumulate in the fetus. affect mental development of children. BEI: lead in blood.

Sulfur Dioxide

strong irritant to the respiratory tract, eyes, skin and mucous membranes.

Teratogen

substance that causes birth defects in developing fetus. examples, thalidomide, ethanol, lead.

Asphyxiants

substances that prevent oxygen from reaching cells. simple asphyxiant: displaces oxygen in atmopsphere, Nitrogen, Argon, Helium.

Industries accounting for the highest percentage of cases of occupational dermatitis

synthetic resin manufacturing 8% Tanneries 4%, oil refining 3%, automobile manufacturing industry 4%

Ames Tet

test to determine mutagenicity of a substance bacteria salmonella typhimurium subjected to substance. DNA of bacteria is examined for damage.

metabolism

the transformation of chemicals in the body also known as biotransformation. make chemicals more water soluble for excretion.

Synergistic effects

total effects of separate chemicals is greater than individual effects (asbestos and smoking. )

dissolution

transport of materials through the blood to body organs such as the liver or kidneys once the particle is absorbed.

Asbestos

used in commercial fire insulation. still used in brake manufacturing. Chrysotile, amosite, crocidolite, tremolite. fibers enter the lungs causing scar tissue to form. health effects: asbestos, mesothelioma, lung cancer, 30 year latency period. ability for asbestos to make fibers (dust) is called friability.

LD50

used to determine chemical potency. as a means of comparing chemicals. to determine dose levels for future larger studies.

Liver

when the liver acts on a xenobiotic, the reactions are designed to; make compounds more polar, make the compound easier excrete, detoxify the material.

Route of exposure (producing greatest effects)

with the exception of intravenous administration, inhalation is usually the most effective followed by intrapertoneal, subcutaneous, intramuscular, intradermal oral and topical.