ENVIRONMENTAL AND OCCUPATIONAL TOXICANTS

DEFINITION OF TERMS: CARBON MONOXIDE

 TOXICOLOGY:  CO
 The study of how natural or synthetic cause undesirable  Colorless, odorless, tasteless, non-irritating gas
effects in living organism  Byproduct of incomplete combustion
 OCCUPATIONAL TOXICOLOGY  Average concentration in the atmosphere: 0.1 ppm
 Deals with chemicals in the workplace  In heavy traffic: may exceed 100 ppm
 Identify agents of concern
 Define the conditions leading to their safe Define the Mechanism of Action
conditions leading to their safe use  Combines reversibly with the oxygen-binding sites of
 Prevent absorption of harmful amounts hemoglobin
 Guidelines: threshold limit values (TLV)  Has an affinity for hemoglobin about 220 times that of oxygen
 ENVIRONMENTAL TOXICOLOGY  Carboxyhemoglobin – product formed, cannot transport oxygen;
 Deals with the potentially deleterious impact of chemicals interferes with the dissociation of oxygen from remaining
(pollutants in the environment) on living organisms oxyhemoglobin  reducing transfer of oxygen to tissues
 Environment – includes all surroundings (air, water, soil)
 Air pollution, chemicals used in agriculture, foo processing, Clinical Effects
etc  Principal signs of intoxication: hypoxia & progress in sequence:
 Guidelines: Acceptable Daily Intake (ADI) 1. psychomotor impairment
2. headache & tightness in the temporal area
TOXICOLOGIC TERMS 3. confusion & loss of visual acuity
 HAZARD 4. tachycardia, tachypnea, syncope, coma
 The ability of a chemical to cause injury in a given situation 5. deep coma, shock, convulsions, respiratory failure
or setting
 To assess  need knowledge on the chemical’s inherent Treatment
toxicity and amounts to which individuals are liable to be  Acute intoxication:
exposed  removal from exposure
 RISK  maintenance of respiration
 The expected frequency of the occurrence of an undesirable  administration of oxygen
effect arising from exposure to a substance
 Estimation of risk  use of dose-response data &
SULFUR DIOXIDE
extrapolation from the observed relationships to the
expected responses at doses occurring in actual situations  SO2
 ROUTES OF EXPOSURE  Colorless, irritant gas
 Route of entry into the body differs indifferent exposure  Generated primarily by the combustion of sulfur-containing fossil
situations fuels
 Industrial setting – inhalation is the major route of entry
 Other routes: transdermal (important route), oral ingestion Mechanism of Action
(minor)  On contact with membranes, SO2 forms sulfurous acid_severe
 DURATION OF EXPOSURE irritant effects on the eyes, mucous membranes and skin
 Acute exposure – a single or multiple exposures occurring  Approx 90% of inhaled SO2 is absorbed in the URT
over 1 or 2 days  Exposure to 5 ppm for 10 minutes leads to increased resistance
 Chronic exposure – multiple exposures continuing over a to airflow in humans
longer period of time
 Occupational setting – both acute and chronic may occur Clinical Effects & Treatment
 Chemicals in the environmental exposure – chronic exposure  Signs & symptoms of intoxication: irritation of the eyes, nose,
throat reflex bronchoconstriction
ENVIRONMENTAL IMPACT  Severe exposure  delayed onset pulmonary edema
 Prediction is based on the following properties of chemical  Chronic exposure  aggravation of chronic cardiopulmonary
agents: disease
 Degradability  Treatment is non-specific; therapeutic maneuvers to address
 Mobility through air, water and soil respiratory tract irritation
 Bioaccumulation
 Biomagnification NITROGEN OXIDES
 BIOACCUMULATION  NO2
 The accumulation of toxic chemicals in living things through  Brownish, irritant gas
consumption of food or water  Associated with fires; also formed from fresh silage
 BIOMAGNIFICATION
 The process by which a contaminant, which may be hardly Mechanism of Action
detectable in water, may be magnified or concentrated as it  Deep lung irritant, may cause pulmonary edema
passes up the food chain  Type I alveoli chiefly affected in acute exposure
 Exposure to:
AIR POLLUTANTS  25 ppm – irritating to some individuals
 Five major substances that account for 98% of air pollution:  50 ppm – moderately irritating to eyes, nose
 Carbon monoxide – 52%  50 ppm for 1 hour – pulmonary edema, subacute or chronic
 Sulfur oxides – 14% pulmonary lesions
 Hydrocarbons – 14%  100 ppm – pulmonary edema, death
 Nitrogen oxides – 14%
 Particulate matter – 4% Clinical Effects
 Major sources:  Acute exposure  irritation of eyes & nose, cough, mucoid or
 Transportation frothy sputum production, dyspnea, chest pain
 Industry  Clinical signs may subside in 2 weeks
 Generation of electric power  Patient may pass into a 2nd stage of abruptly increasing severity,
 Space heating w/recurring edema & fibrotic destruction of terminal bronchioles
 Waste Disposal  Therapeutic measures employed for the management of deep
lung irritation and non-cardiogenic pulmonary edema
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OZONE
 O3
 Bluish irritant gas, occurs normally in the atmosphere (important
absorbent of UV light)
 In the workplace: can occur around high-voltage electrical
equipment, ozone-producing devices used for air & water
purification
 An important oxidant found in polluted urban air
Clinical Effects & Treatment
 Irritant of mucous membranes; causes shallow rapid breathing,
decrease in pulmonary compliance
 Mild exposure  Upper respiratory tract irritation
 Severe exposure  deep lung irritation, pulmonary edema
 O3 toxicity may result from the formation of reactive free
radicals
 Exposure to
 0.1 ppm for 10-30 mins  irritation & dryness of the throat
 > 0.1 ppm  changes in visual acuity, substernal pain,
dyspnea
 > 0.8 ppm  impaired pulmonary function
 Airway responsiveness & inflammation observed in humans
 Therapeutic measures employed for the management of deep
lung irritation and non- cardiogenic pulmonary edems
SOLVENTS
 Solvent – a substance, usually a liquid, that can dissolve other
substances
1. Halogenated Aliphatic Hydrocarbons
2. Aromatic Hydrocarbons
HALOGENATED ALIPHATIC HYDROCARBONS
 Agents used as industrial solvents, degreasing agents, cleaning
agents
 Carbon tetrachloride
chloroform
trichloroethylene
tetrachloroethylene (perchloroethylene)
1,1,1-trichloroethylene (methyl chloroform)
ORGANOCHLORINE INSECTICIDES
 Classified into 4 groups:
1. DDT (chlorophenothane) & its analogs
2. Benzene hexachlorides
3. Cyclodienes
4. Toxaphenes
 Are aryl, carbocyclic, or heterocyclic compounds containing
chlorine substituents
 Can be absorbed through skin, by inhalation or oral ingestion
Human toxicology
 Interfere with inactivation of the sodium channel in excitable
membranes, cause rapid repetitive firing in neurons
 Calcium ion transport is inhibited
 Major effect is CNS stimulation
 Tremor (DDT) or convulsion may be the first sign of intoxication
Environmental Toxicology
 Persistent chemicals
 Degradation is slow compared with other insecticides
 Bioaccumulation (particularly in aquatic ecosystems)
 Presence or organic matter in soils favors adsorption onto soil
particles; poor adsorption in sandy soil
ORGANOPHOSPHOROUS INSECTICIDES
 Utilized to combat a large variety of pests
 Absorbed by the skin, respiratory & gastrointestinal tracts
 Biotransformation is rapid
Human Toxicology
 Inhibition of acetylcholinesterase, accumulation of acetylcholine
 Exposure to high concentrations  altered neurologic &
cognitive functions, psychological symptoms
 Phosphorylation of neuropathy target esterase  delayed
neurotoxicity (polyneuropathy, paralysis & axonal degeneration)
Environmental Toxicology
 Not considered to be persistent pesticides
 Relatively unstable and break down in the environment

Mechanism of Action & Clinical Effects CARBAMATE INSECTICIDES

 Depressants of the CNS in humans (chloroform most potent)  Inhibit acetylcholinesterase by carbamoylation of the esteratic
 Chronic exposure to tetrachloroethylene  impaired memory, site
peripheral neuropathy  Toxic properties similar to organophosphates
 Hepatotoxicity ( carbon tetrachloride most potent)  Clinical effects are of shorter duration than those of
 Nephrotoxicity – carbon tetrachloride, chloroform, organophosphates
trichloroethylene  Not persistent pesticides
 Management of toxicity depends on organ involved
BOTANICAL INSECTICIDES
AROMATIC HYDROCARBONS
 Derived from natural sources: nicotine, rotenone, pyrethrum
Benzene  Nicotine is rapidly absorbed from mucosal surfaces
 Widely used, used as an intermediate in the synthesis of other  Nicotine reacts with the acetylcholine receptor of the
chemicals postsynaptic membrane, resulting in depolarization
 Acute toxic effect: depression of the CNS  Toxic doses  stimulation rapidly followed by blockade of
 Exposure to: transmission
 7500 ppm for 30 mins_fatal  Rotenone produces gastrointestinal irritation with oral ingestion
 3000 ppm_euphoria, nausea, locomotor problems, coma  Conjunctivitis, dermatitis, pharyngitis, rhinitis can occur
 250-500 ppm_vertigo, drowsiness, headcahe, nausea  Treatment is symptomatic
 Chronic exposure: injury to the bone marrow_aplastic anemia,  Pyrethrum has six known insecticidal esters
leukopenia, pancytopenia, or thrombocytopenia  Synthetic pyrethroids account for 30% of insecticide usage
worldwide
Toluene (methylbenzene)  May be absorbed after inhalation or ingestion; skin
 CNS depressant absorption not significant
 Exposure to:  Esters are extensively biotransformed, not highly toxic to
 800 ppm_severe fatigue, ataxia mammals
 10,00 ppm_rapid loss of consciousness  Major site of action: CNS
 Chronic effects: not clear  Excitation, convulsions, tetanic paralysis can occur
 Targets are: voltage-gated sodium, calcium & chloride channels,
peripheral-type benzodiazepine receptors
INSECTICIDES
 Symptomatic treatment employed
1. Organochlorine Insecticides
2. Organophosphorous Insecticides
3. Carbamate Insecticides HERBICIDES
4. Botanical Insecticides 1. Chloryphenoxy Herbicides
2. Bipyridyl Herbicides

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CHLORYPHENOXY HERBICIDES  Widely distributed initially to soft tissues:
 2,4-Dichlorophenoxyacetic acid (2,4-D);  bone marrow, brain, kidney, liver, muscle,
2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) and their salts &  gonads  subperiosteal surface of bone bone matrix
esters are the major compounds used to kill weeds  Crosses the placenta
 2,4-D in large doses  coma, generalized muscle hypotonia  Multisystemic toxic effects mediated by multiple modes of
 2,4,5-D  coma may occur, less evident muscular dysfunction action:
 inhibition of enzymatic function
 interference with the action of essential cations
BIPYRIDYL HERBICIDES
 disturbance of cellular redox status
 Paraquat is the most important agent  alteration of the structure of cell membranes & receptors
 MOA: single-electron reduction of the herbicide to free radical  Nervous system
species  Blood
 Clinical effects: oral exposure_Gastrointestinal irritation  Kidneys
(hematemesis, bloody stools)  Reproductive organs
 delayed toxicity_respiratory distress, congestive  Gastrointestinal tract
hemorrhagic pulomonary edema with widespread cellular  Cardiovascular system
proliferation
 hepatic, renal, myocardial involvement
 Interval between ingestion and death may be several weeks

Treatment
 Prompt removal of paraquat in the GIT:
 use of gastric lavage, cathartics, adsorbents to prevent
further absorption
 Success of treatment in fewer than 50%

ENVIRONMENTAL POLLUTANTS
1. Polychlorinated biphenyls
2. Endocrine disruptors

POLYCHLORINATED BIPHENYLS
 PCBs, coplanar biphenyls
 Used as dielectric & heat transfer fluids, plasticizers, wax
extenders, flame retardants
 Use has been terminated but persist in the environment
 Highly stable, highly lipophilic, poorly metabolized, very resistant
to environmental degradation, bioaccumulate in food chain
 Food is the major source in humans

Clinical effects
 Effects on human reproduction & development, carcinogenicity
have yet to be established
 Polychlorinated dibenzo-p-dioxins (PCDDs) or Dioxins,
Polychlorinated dibenzofurans (PCDFs): unwanted byproducts of
improperly controlled combustion processes, contaminants of
the environment

ENDOCRINE DISRUPTORS
 Phytoestrogens, mycoestrogens, industrial Phytoestrogens,
mycoestrogens, industrial chemicals such as organochlorine,
PCBs chemicals such as organochlorine, PCBs
 Estrogen-like or anti-androgenic properties Estrogen-like or anti-
androgenic properties
 Increasing environmental contamination, Increasing
environmental contamination, bioaccumulation

HEAVY METALS
1. Lead
2. Arsenic
3. Mercury

LEAD
 Lead poisoning is one of the oldest occupational and
environmental diseases
 Lead continues to have widespread application: production of
storage batteries, metal alloys, solder, glass, plastics, ceramics
 Low-level lead exposure

Pharmacokinetics
 Inorganic lead is slowly but consistently absorbed via the
respiratory and GI tracts
 Organic leads well absorbed through the skin
 Most common cause of industrial poisoning – lead dust
 Non-industrial exposure – primary route of exposure is intestinal
 Lead is bound to erythrocytes

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