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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 ´ ' 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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Halogenated Alip!atic
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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Halogenated Alip!atic
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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Aromatic Hydrocar+ons
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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Aromatic Hydrocar+ons
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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Organoc!lorine #esticides
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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Organoc!lorine #esticides
Environmental Toxicology
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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Organop!osp!orus #esticides
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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Organop!osp!orus #esticides
Environmental Toxicology
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%