23.1.

PRINCIPLESOF TOXICOLOGY
23.1.1.
3.1. Introduction
has
Tpe termm toICology has
b icology
been
ison, Greck word derived from ihe
poiso
miT study of loricum Laln and Cteek
log SCENCE mean1ng arrow
poison ard toxicum
noIsons living
organisns.
on TOycotogy can be detned
Traditionally
and Latm word
enobiotics science of poiso whch toxicology can be literally as study of
or

th the includes interacton ofdefincd stud of

physiologicalCOmpartments of mammas exogenus agents
NMa
hieu Joseph
Bonaventur
the father of modern 187-1853, Spaniard atend1ng a

alogy,in 1815 detailing aboutloxicology

the
He wrotc his
first
phiy stcian
book adverse effects on
general
is

of
The chemical exposurc o epenmenlal animals chemical
hvided into the tollowing four classes by the to
d1tferent chemieals has been
1) Acute: It can be deTined as toxicologists:
eposure to a
chermcal for not more than 24 hours
Sub-Acute: Il can be delined as repeated
month or lesser. exposure a chemical for about to
1

)Sub-Chronic: It can be defined as

exposure to a chemical for I to 3 months
4) Chronic: It can be defined as
exposure to a chemical for more than 3 months
23.1.2. Acute Toxicity
)The word acute refers to short duration with respect to the eftect or
exposure.
In
experimental toxicology. it is defined as such studies in which the dosing
ISdone either once in a day or
multuple times but from I day irrespective of
the total study duration which might extend to 2 weeks.
) In clinical medicine. it refers to severe and sudden effect having rapid onset
ol action. It studies the effect of single dose on a specific anmal species

r o r the first time J.W. Trevan in 1927 introduced LDo to conduct the acute
In this testing. the test product is administered at
OXICIty study on rats.
uierent doses for 14 days after which the biochemical. pathological,
recorded and all the motalities
SOTOgical and morphological changes are
are also recorded. LD%
UScd by the test substance duning the expenment
studies.
s theretfore used as an indicator of acute toxICIty
within 24 hours as an acute
Usual single dose or multiple doses given
a
are
the expOsure
almost within hours after
PSure whose toxicity occurs
6 as acute exposure.
AOSure for short duration is known
 kogy
Acute ENfect: Fast pard acton'reac tion, taking place within quant.
u e timeline 0 < hours < 14 days) alier the administration of a l e
doage or when eipused to some u t of
radiation. single
S) Acute systemic testing an be descnbed by guidelines of
c
Organisa
sation
tconomic Cooperation and Development (OECD). for
Acute Dermal Tocity
(OtcD Toa:)
) Acute Inhalation tovucity (COECD TGa).
Fiued dose proxedure (OECD TGa0).
Acute Toxuc Class method (OECD TGa23). and
vCp-and-Dow a Proedure (OECD TG:)
9)
ED: It is the edian effective dose. ic, the dose tor which
half (s0%.
the animals exh1bit an ettect (E) and halt of the animals exhibit
k) of
The effect may be defined as a specitic tONIC cvent e-g-. tremors) and
sometimes defined as lethality i
(LDo). Other subscipts may be used
o
designate the percentage of animals
affected. For
example, the ED
ED are the doses at which 0* or W* o the animals, and
demonstrate the effect. respectivel

23.1.3. Sub-Acute Toxicity

1) Sub-acute toxucity studies are conducted as

determining the dosage

levels that has to be used in chronic and for ange-finding studies
studies for duration of 6 months to 2 years and up to ) sub-chronic
days, respectively.
2)These studies are conducted tor duration of weeks in order
the to evaluate
potential adverse ettects of a new drug.
3) They help in supportung the initial clinical tnal phases where the
duration might vary from I to 4 week treatment
4)
Progression and regression of
drug-induced lesions can be assessed by these
studies but the duration generally remains insufficient tor identifying all the
secondary etfect that might anse during long-term clinical use or
carcinogenicity testing or chronic toxicity studies during

23.1.4. Chronic Toxicity

) Chronic toxicity indicates
specific organ system damage which results in the
development of a serious recognisable disease due to
damage. However, in this case damage from subcl1nical
long-term cumulative
exposure builds up
slowly to result in curmulative damage. till the damage exceeds the threshold
level.
)
Eventually, the organ remains no longer normal functional due to severe
damage, thereby resulting in many different types of chronic toxic
3)
Examples of chronic ettects.
toxicity
1)
Long term(several years) ethanol
ingestion in alcoholics result in
Cirrhosis, i
) Several years of lecad
exposure in workmnen causes disease. kidney
11) Long term
cigarette smokers develop chronic bronchitis, and
I)
Pulmonary fibrosis, also known as black lung disease develops in co
miners when exposed for longer times.