short and long-term exposure limits = the rules and regulations set by governmental bodies

definition  from handout: legally binding limits issued by the Occupational Safety and Health Administration (OSHA).

the increasing concentration of a substance in the environment as the result of environmental peristence and physical properties (eg. lipid solubility) that leads to accumulation in biologic tissues

*** the buildiup of potentially toxic chemicals in an organism when the rate of intake exceeds the rate of elimination ***

Contaminant gets magnified as it goes up the food chain

Although the concentration of a contaminant may be virtually undetectable in water, it may be magnified hundreds or thousands of time as the contaminant passes up the food chain

the ability of a chemical agent to cause injury in a given situation or setting; the conditions of use and exposure are primary considerations

it is often a description based on subjective estimates rather than objective evaluation

the expected frequency of the occurrence of an undesirable effect arising from exposure to a chemical or physical agent

use dose-response data to estimate; also extrapolation of observed relationships between expected response at certain doses

carbon monoxide (50% of total amount of air pollutants); sulfur oxides; hydrocarbons; particulate matter (smoke particles); nitrogen oxides

1) carbon monoxide

2) sulfur dioxide

3) nitrogen oxides

4) ozone (O₃)

odorless, colorless gas that competes with oxygen for Hg

affinity of CO for Hg is more than 200-fold greater than that of oxygen

CO causes tissue hypoxia --> headache --> confusion, decreased visual acuity, tachycardia, syncope, coma, seizures, and death

collapse and syncope when 40% Hg is converted to carboxyhemoglobin --> irreversible brain damage due to hypoxia

treatment: remove source of CO and 100% oxygen; hyperbaric oxygen accelerates the clearance of carbon monoxide

is a colorless, irritating gas formed from the combustion of fossil fuels

effects: forms sulfurous acid on contact with moist mucous membranes -->conjunctival and bronchial irritation are the primary signs of exposure --> heavy exposure may lead to delayed pulmonary edema --> chronic low-level exposure = CARDIOPULMONARY DZ

Tx: removal from exposure to SO2 and relief of irritation and inflammation constitute the major tx

Nitrogen dioxide = brownish irritant gas; formed in fires and in silage on farms

MOA: NO₂ is realtively insoluble and causes deep lung irritation and pulmonary edema --> affects type I alveoli cells; at higher concentrations, affects both type I and type II alveoli cells

acute exposure signs and sx: nose, cough, mucoid or frothy sputum production, dyspnea, and chest pain

farm works in SILOS may die rapidly from acute pulmonary edema; irritation of the eyes, nose, and throat is common

Tx: nothing specific --> supportive for pulmonary edema

--> maintenance of gas exchange with adequate oxygenation and alveolar ventilation. Drug therapy may include bronchodilators, sedatives, and antibiotics

bluish irritant gas produced in air and water purification devices and in electrical fields

MOA: irritant of mucous membranes. Mild exposure produces upper respiratory tract irritation. Severe exposure can cause deep lung irritation, with pulmonary edema when inhaled at sufficient concentrations

--> concentration depends on tidal volume!

-->O₃ toxicity may result from the formation of reactive free radicals

-morphologic and biochemical changes are the result of both direct injury and secondary responses to the initial damage

Tx: There is no specific treatment --> Management depends on therapeutic measures used for deep lung irritation and noncardiogenic pulmonary edema

carbon tetracholoride

chloroform

trichlorethyene

methyl chloroform

industrial solvents, degreasing agents, and cleaning agents

• central nervous system depression
  
• liver injury
• kidney injury
• some degree of cardiotoxicity
• acute effects: nausea, vertigo, locomotor disturbances, headache, and coma
• long term exposure = peripheral neuropathy

tx: removal from exposure --> support vital signs!

• CNS depression with ataxia and coma
• long term exposure with benezen is associated with hematotoxicity
• thrombocytopenia
• aplastic anemia
• pancytopenia
• hematologic cancers, espcially leukemia

aromatic hydrocarbon

toxicities:

• excess blood cancers at current PEL
• euphoria, nausea, locomotor problems, and coma; vertigo, drowsiness, headache, and nausea
• MOST SERIOUS = bone marrow injury
• Aplastic anemia, leukopenia, pancytopenia, and thrombocytopenia

aromatic hydrocarbon

toxicity: CNS depression, skin and eye irritant, FETOTOXIC

fatigue and ataxia

10,000 ppm can produce rapid loss of consciousness

aromatic hydrocarbon

toxicity: CNS depressant

Skin irritant

they interfere with inactivation of the sodium channel in excitable membranes and cause rapid repetitive firing in most neurons

calcium ion transport is inhibited --> imparied repolarization and enchanced excitability of neurons

major effect is CNS stimulation

termor one of first manifestations --> convulsions (this is for DDT)

other drugs present immediately with convulsions

potential carcinogenic properities - endocrine pathway disruption is the possible mechanism (animal studies)

prepubertal exposure to DDT and brain cancer; also recent risk of testicular cancer; risk of non-Hodgkin's lymphoma in persons with elevated oxychlordane residues

absorbed by skin, respiratory, and GI tract; biotransformation is rapid

inhibition of acetylcholinesterase through phosphorylation of the esteratic site --> signs and sx associated with accumulation of ACh

some agents have direct cholinergic activity

can target an esterase that results in progressive demyelination of the longest nerves

Polyneuropathy: burning and tingling sensations, particularly in the feet, with motor weakness a few days later. Sensory and motor difficulties may extend to the legs and hands. Gait is affected, and ataxia may be present. Central nervous system and autonomic changes may develop even later.

inhibit acetylcholinesterase by carbamoylation of the esteratic site - sx similar to that of organophosphorus pesticides, but sx are shorter in duration with carbamates

sx range from minor intoxication to lethality

do not treat with pralidoxime

nclude nicotine, rotenone, and pyrethrum

Nicotine reacts with the acetylcholine receptor of the postsynaptic membrane (sympathetic and parasympathetic ganglia, neuromuscular junction), resulting in depolarization of the membrane

esters are extensively biotransformed

the major site of toxic action is the central nervous system; excitation, convulsions, and tetanic paralysis can occur. Voltage-gated sodium, calcium, and chloride channels are considered targets, as well as peripheral-type benzodiazepine receptors

respiratory and skin problems, neurological complaints

Chlorophenoxy Herbicides

used in agent orange

In humans, 2,4-D in large doses can cause coma and generalized muscle hypotonia. Rarely, muscle weakness and marked hypotonia may persist for several weeks.

In laboratory animals, signs of liver and kidney dysfunction

causal link between 2,4-D and non-Hodgkin's lymphoma

Paraquat is the most important agent of this class

involves single-electron reduction of the herbicide to free radical species.

human lethal dosage at 50–500 mg/kg

accumulates slowly in the lung by an active process and causes lung edema, alveolitis, and progressive fibrosis.

FREE RADICAL FORMATION!!

First signs/sx: hematemesis and bloody stools -->delayed toxicity occurs = respiratory distress and development of congestive hemorrhagic pulmonary edema

hepatic, renal, or myocardial involvement

The interval between ingestion and death may be several weeks --> Remove from GI immediately via lavage

dielectric and transfer fluids - very lipophillic, poorly metabolized, and resistant to environment degradation

bioaccumulation in food chains

carcinogeneic

teratogeneic

clinical signs: dermatologic problems (chloracne, folliculitis, erythema, dryness, rash, hyperkeratosis, hyperpigmentation), some hepatic involvement, and elevated plasma triglycerides

wasting syndrome (severe wt loss with muscle atrophy), thymic atrophy, epidermal changes, hepatotoxicity, immunotoxicity,

,3,7,8-tetrachlorodibenzodioxin (TCDD, dioxin)

one of the most toxic environmental pollutants

increased risk for cancers such as melanoma, breast, prostate

lung disease/cancer/ mesothelioma

Other cancers including colon cancer, laryngeal cancer, stomach cancer, and perhaps even lymphoma are increased in asbestos-exposed patients.

shaking chills, cough, fever, and malaise

transient pneumonia

chronic exposure = pulmonary fibrosis

severe kidney complications

halogenated hydrocarbon

anesthetic

dichlorodiphenyltrichloroethane

= organochlorine pesticide

parathion

organophosphate

paraquat

= Bipyridyl Herbicides

220 greater affinity

1000 ppm for 50% inhibition