3. Occupational & Environmental Toxicology

8/19/2019 3. Occupational & Environmental Toxicology

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Occupational &

EnvironmentalToxicology

Erwin P. Carabeo, M.D., FPCP

Department of Pharmacology

San Beda College of Medicine


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Occupational Toxicolgy

Chemicals found in the worplace

Ma!or emphasis of occupational to"icolgy#

$. identify agents of concern

%. identify the diseases they cause &acute ' chronic(

). define conditions under which they could be used

safely *. pre+ent absorption of harmful amounts of these

chemicals


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Workplace Regulations

PES

- permissible e"posure limits

- ha+e the power of law

- S/0

12

- threshold limit +alues

- reference points in the e+aluation of potential

worplace e"posures


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Environmental Toxicology

deals with the potentially deleterious impact of chemicals

&pollutants( on li+ing organisms

en+ironment# air, soil and water


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ADI

acceptable daily intae

daily intae of chemical from food that during an entire

lifetime appears to be without an appreciable ris

F034/


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Ecotoxicology

to"ic effects of chemical and physical agents on

populations and communities of li+ing organisms

includes the transfer pathways of agents and interactions

with the en+ironment

traditional to"icology# to"ic effects on indi+idual organism


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Toxicologic Terms

Hazard 5 ability of the chemical to cause in!ury in a

gi+en situation or setting6 assessment is based inherent

to"icity of the substance and the amounts to whichindi+iduals are liable to be e"posed

Risk 5 the e"pected fre7uency of the occurrence of an

undesirable effect arising from e"posure to chemical orphysical agent


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Toxicologic Terms

Routes o Exposure 5 route of entry of chemicals into

the body

- industrial setting# inhalational is the ma!or route of entry

- atmospheric pollutants# inhalation and transdermal

routes

- water and soil pollutants# inhalation, ingestion and

dermal contact


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Toxicologic Terms

Duration o Exposure 5 length of e"posure to

chemicals

- acute exposure# single or multiple e"posures lastingfrom seconds to $ or % days

- c!ronic exposure# multiple e"posures continuing o+er

a longer period of time


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"!emical and #!ysical "!aracteristics t!at

Determine Environmental Impact o Toxicants$

$. degradability of the substance

%. its mobility through air, water and soil

). whether or not bioaccumulation occurs

*. transport and biomagnification through foodchains


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%%%

1he pollutants that ha+e the widest

en+ironmental impact

8 are poorly degradable

8 are relati+ely mobile in air, water and soil

8 e"hibit bioaccumulation 8 e"hibit biomagnification


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ioaccumulation 5 accumulation of chemical within the

tissues of an organism that occurs when the intae of a

long-lasting contaminant e"ceeds the organism9s ability

to metaboli:e or e"crete the substance

iomagniication 5 e"ponential increase in the

concentration of a contaminant as it passes up the foodchain


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Air #ollutants


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' (a)or Air #ollutants

carbon mono"ide &C( 5 ;%<

sulfur o"ides 5 $*<

hydrocarbons 5 $*<

nitrogen o"ides 5 $*<

particulate matter 5 *<


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*ources o Air #ollutants

transportation

industry

generation of electricity

space heating

refuse disposal


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"ar+on (onoxide

colorless, odorless, tasteless and non-irritating

gas

by product of incomplete combustion

a+erage concentration in atmosphere# =.$ ppm

in hea+y traffic# > $== ppm


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"ar+on (onoxide

(ec!anism o Action

combines re+ersibly with % binding sites of

hemoglobincarbo"yhemoglobin failure of

o"ygen transport and transfer of o"ygen totissues

affinity for hemoglobin is %%=? that of %

brain and heart are the most affected


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"ar+on (onoxide

#rincipal *igns o "O Intoxication$

psychomotor impairment

headache

confusion and loss of +isual acuity

tachycardia, tachypnea syncope and coma

deep coma, con+ulsions, shoc and respiratory

failure


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"ar+on (onoxide

Treatment

for acute into"ication# remo+al from e"posure

source and maintenance of respiration

o"ygen administration#

- room air# elimination half time of C 5 )%= min

- $==< o"ygen# @= minutes

- hyperbaric o"ygen &%-) atm(# %= minutes


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*ulur Dioxide

S%

colorless irritant gas

generated by the combustion of sulfur-containing

fossil fuels


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*ulur Dioxide

(ec!anism o Action

on contact with moist membranes sulfurous

acidse+ere irritant effects on eyes, mucus

membranes and sin

inhalation of S%# bronchoconstriction


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*ulur Dioxide

"linical Eect and Treatment

irritation of the eyes, nose and throat

refle" bronchoconstriction

in asthmatics# acute asthmatic attac

no specific treatment for S%6 treatment of the

irritation of respiratory tract and asthma


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,itrogen Oxides

nitrogen dio"ide &A%(

brownish irritant gas associated with fires


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,itrogen Oxides

(ec!anism o Action

insoluble deep lung irritant capable of producing

pulmonary edema

;= ppm# moderately irritating to the eyes and

nose

;= ppm for $ hour# pulmonary edema or chronicpulmonary lesions

$== ppm# pulmonary edema and death


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,itrogen Oxides

"linical Eects

acute e"posure# irritation of the eyes and nose,

cough, mucoid or frothy sputum, dyspnea, chest

pain

clinical signs may subside in about % wees

second stage# abruptly increasing se+erity,recurring pulmonary edema and fibrotic

destruction of terminal bronchioles


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,itrogen Oxides

Treatment

no specific treatment for acute into"ication

management of deep lung irritation and

pulmonary edema# ade7uate o"ygenation and

al+eolar +entilation

drugs# bronchodilators, sedati+es and antibiotics


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Ozone

)

bluish irritant gas normally occurring in the

atmosphere

absorbent of 2 light

worplace# o:one producing de+ices for air and

water purification, high +oltage electrical

e7uipment also found in polluted urban air


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Ozone

"linical Eects

effects resemble that of radiation

=.$ ppm for $=-)= min# irritation and dryness of

the throat

>=.$ ppm# changes in +isual acuity, substernal

pain and dyspnea >=.@ ppm# impairment of pulmonary function


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Ozone

Treatment

similar to treatment of Aitrogen "ide e"posure


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*olvents


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Halogenated Alip!atic

Hydrocar+ons

used as# industrial sol+ents, degreasing agents,

cleaning agents

carbon tetrachloride, chloroform,

trichloroethylene, tetrachloroethylene, methyl

chloroform

CCl* and trichloroethylene ha+e been remo+edfrom the worplace


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Hydrocar+ons

(ec!anism o Action & "linical Eects

CAS depression6 chloroform 5 most potent

chronic e"posure# impaired memory and

peripheral neuropathy

hepatoto"icity6 CCl* 5 most potent

nephroto"icity

carcinogenicity


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Hydrocar+ons

Treatment

no specific treatment for acute into"ication

management depends on the organ system

in+ol+ed


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Aromatic Hydrocar+ons

E,-E,E

- component of premium gasoline

- acute to"ic effect# CAS depression

- %;=-;== ppm# +ertigo, drowsiness, headache

- >)=== ppm# euphoria, nausea, locomotorproblems, coma

- ;== ppm for )= min# fatal- chronic e"posure# bone marrow to"icity aplastic anemia, leuemia, lymphoma, myeloma


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TO./E,E &Methylben:ene(

- CAS depressant, sin and eye irritant,

- fetoto"ic

- at @== ppm# se+ere fatigue and ata"ia

- at $=,=== ppm# rapid loss of consciousness


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01.E,E &Dimethylben:ene(

- substitute for ben:ene in degreasing operations

- no myeloto"ic properties of ben:ene

- CAS depressant and sin irritant


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#esticides


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Organoc!lorine #esticides

DD1 &chlorophenotane(

ben:ene he"achlorides

cyclodienes

to"aphenes


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Human Toxicology interfere with acti+ation of sodium channels and

inhibition of Calcium ion transport enhanced

e"citability of neurons CAS stimulation DD1# tremors con+ulsions no specific treatment of acute into"ication increased cancer ris e"posed to halogenated

hydrocarbon pesticides# brain cancer &DDE(,testicular cancer &DDE(, non-/odgin9slymphoma


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considered as persistent chemicals because of

slow degradation

bioaccumulation in a7uatic ecosystems

induce significant abnormalities in the endocrine

balance of sensiti+e animal and bird species


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Organop!osp!orus #esticides

used to combat a wide +ariety of pets

based on compounds which were de+eloped for

use as war gases &soman, sarin and tabun(

absorbed by the sin, respiratory and tracts

undergoes rapid biotransformation


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Human Toxicology

mechanism of action# inhibition of

acetylcholinesterase accumulation of acetyl

choline6 some may ha+e direct cholinergicacti+ity

altered cogniti+e and neurologic functions

inhibition of neuropathy target esterase progressi+e demyelination of neurons

paralysis


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not considered as persistent pesticides

relati+ely unstable and breadown in the

en+ironment as a result of hydrolysis and

photolysis

small impact on the en+ironment


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"ar+amate #esticides

mechanism of action# inhibition of

acetylcholinesterase

possess the to"ic properties associated with

organophosphorus pesticides

clinical effects are of shorter duration than those

of organophosphorus pesticides considered to be nonpersistent pesticides


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otanical #esticides

pesticides deri+ed from natural sources

nicotene, rotenone, pyrethrum


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otanical #esticides

,icotene

obtained from the dried lea+es of Nicotiana

tabacum and Nicotiana rustica

rapidly absorbed from mucosal surfaces

reacts with the acetylcholine receptor of the

postsynaptic membrane depolari:ation of the

membrane treatment directed at maintenance of +ital signs

and suppression of con+ulsions


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otanical #esticides

Rotenone

obtained from Derris elliptica, D mallaccensis,

Lonchorpus utilis, L urucu

oral ingestion# irritation

con!uncti+itis, dermatitis, pharyngitis and rhinitis

can also occur

treatment is symptomatic


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otanical #esticides

#yret!rum

may be absorbed after ingestion or inhalation6

absorption from sin is not significant

not highly to"ic to mammals

CAS effects# e"citation, con+ulsions, tetanic

paralysis

treatment directed at management of symptoms6i+ermectin, pentobarbital, mephenesin


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Her+icides


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"!lorop!enoxy Her+icides

%,* Dichloropheno"yacetic acid &%,*-D(,%,*,;-

trichloropheno"yacetic acid &%,*,;-1(

used for the destruction of weeds

to"icity ratings#

* 5 human lethal dose ;= 5 ;== mg3g

) 5 human lethal dose ;== 5 ;=== mg3g

large doses# coma and generali:ed hypotonia confirmed lin with non /odgin9s lymphoma


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2lyp!osate

most widely used herbicide in the world

contact herbicide# absorbed through the lea+es

and roots

significant eye and sin irritant

ha+e little persistence and lower to"icity than

other herbicides

no specific treatment for glyphosate to"icity isa+ailable


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ipyridil Her+icides

#ara3uat 5 most important agent in this class

mechanism of action# reduction to free radical

species

to"icity rating of * &human lethal dose of ;=-;==

mg3g(

after oral e"posure# hematemesis and bloody

stools delayed to"icity# lung edema, al+eolitis and

progressi+e fibrosis


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ipyridyl Her+icides

hepatic, renal or myocardial in+ol+ement

inter+al between ingestion and death may be

se+eral wees

treatment# gastric la+age, use of cathartics,

use of adsorbents

after absorption, treatment is successful in

less than ;=< of cases


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Environmental#ollutants


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#olyc!lorinated ip!enyls

PCB9s, coplanar biphenyls

uses# heat transfer fluids, lubricating oils,

plastici:ers, wa" e"tenders and flame retardants

industrial use and manufacture was terminated

in the S in $

persist in the en+ironment# highly stable, highly

lipohilic, poorly metaboli:ed, +ery resistant todegradation, bioaccumulation in food chains

foods# ma!or source of PCB residues in humans


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#olyc!lorinated ip!enyls

occupational e"posure to PCBs# dermatologic

problems, hepatic in+ol+ement and ele+ated

plasma triglycerides

increase in +arious cancers# melanoma, breast,pancreas and thyroid

deficits in childhood intellectual function was

seen in children born to mothers who had eatenlarge 7uantities of fish contaminated with PCBs


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As+estos

has been used widely for o+er $== years

has been shown to cause progressi+e lung

disease characteri:ed by fibrotic process

higher le+els of e"posure# asbestosis

cigarette smoing increases the incidence of

asbestos caused lung cancer

other cancers# mesothelioma, colon cancer,laryngeal cancer, stomach cancer, lymphomas


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(etals


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occupational and en+ironmental poisoning

with metals is a ma!or health problem

classic metal poisons# arsenic, lead and

mercury

new occupational e"posure and poisoning#

beryllium, manganese, cadmium and

uranium


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eryllium

light alaline metal6 non sparing 7uality

uses# dental appliances, nuclear weapons,

computer components

highly to"ic by inhalation

inhalation of beryllium particles progressi+e

pulmonary fibrosis &chronic beryllium disease(

and cancer prognosis is poor


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"admium

uses# batteries, pigments, solder, tele+ision,

plating operations, semiconductors, plastics

to"ic by inhalation and ingestion

cadmium fume fe+er# acute respiratory disordercommon in welders6 shaing chills, cough, fe+er

and malaise

chronic e"posure# pulmonary fibrosis, se+ereidney damage


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T!ank you%

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3. Occupational & Environmental Toxicology