Ineffectiveness of the LD 50 test in animals when applied to humans

LightningIce, 2013
LD50 test refers to the median lethal dose of a concentration of the toxic substance that
will kill off half of the sample population it was inoculated into. est animals are fed doses
of the toxin at intervals till half the number of sample animals are dead then the! stop" and
that dosa#e is identified as the ld50. $t was made the toxicolo#! testin# standard durin# the
1%20s to seemin#l! ascertain the toxic dosa#es safe for humans after the! were tested on
animals, eradicatin# lar#e numbers of them and severel! woundin# the rest in the process.
&till used toda! to test toxicit! of man! substances in science, however the results have
often proved otherwise and this test has now been replaced b! man! other accurate non
animal alternatives.

$n the !ear 2000 '& food and dru# administration, started to approved and validate the
accurac! of man! other non animal usa#e test methods to evaluate toxicit! and the ld50
test is no lon#er a re(uirement for dru# manufacturin# approval, thus it has it been phased
out.
)efore this, man! tests were conducted whereb! batches of hi#h number of animals were
needlessl! killed onl! to discover that even when species and sex were kept constant, each
batch of test done in the same lab !ielded different ld50 results, even when done between
different labs, with the species and sex kept constant, the results between different labs
were also different with a hi#h variance. hus no ld50 test can be replicated producin# the
same ld50 value results.
*nimals var! in terms of their different health conditions, biochemical states and s!stemic
states especiall! when excessivel! traumati+ed durin# confinement and experimental
handlin#, this varies exist between individuals of other species as well. *lso if we take into
account how the effects of stress and mishandlin# in the lab wold affect their ph!siolo#ical
conditions alon# with starvations, there can be no accurac! in the test. ,urther more
#enetics, ph!siolo#ical s!stems and thus biochemical conditions cannot be the same
amon#st individuals even if of the same species. Likewise human #enetics and animal #enes
are ver! different which brin#s about different bodil! conditions and molecular states, to
expect the same toxin to work similarl! amon#st different individuals is far from accurate.
est dosa#e is calculated b! wei#ht, this would be like expectin# creatures of different
si+es to still be the same in terms of biochemical compositions or metabolic states.
*nimals are ver! frail and suffer from health inflicts after which the! fade off and die ver!
easil!, the same cannot be said for humans and it isn-t .ust about si+e and mass.

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he biochemistr! of each individual alon# with the ph!siolo#ical health state and poison
assimilation pathwa!s, en+!mes, ph!sical and ph!siolo#ical conditions and (uantum of
metabolites their concentrations and molecules involved in the toxin assimilation pathwa!s
are what makes each individual uni(ue in their capacit! to tolerate, detoxif! or die from
the poisonin#.

Ld50 tests mi#ht be a ver! loosel! #enerali+ed indicator of how the poison will affect a
particular species, but to appl! that to humans would be too inaccurate a predictor. he
ph!siolo#! of most species are alread! ver! well understood ri#ht down to the biochemical,
molecular and #enetics level. /ust knowin# the molecular composition of the toxins and
comparin# them to a ph!siolo#ical bein#0s biochemical and molecular composition will be
sufficient to understand it0s mechanism of action upon in#estion. *ll these can be
additionall! fi#ured out with aids of software and ph!sicall! testin# them out on the livin#
at the risk of harmin# health! entities isn0t .ust cruel and evil, it0s simpl! not as precise or
as clearl! defined if one came to the answer from a biochemical theoretical comparison
and understandin#.

1oison is first assimilated b! the respective #i tract units before bein# metaboli+ed and thus
affectin# the other downstream or#ans. the method of poison assimilation cross species
mi#ht be alike, but their biochemistr! within or#ans of assimilations and metabolic
pathwa!s differ. he ph and en+!mes are also varied across the species, man! lack the
same identical en+!mes that a human ph!siolo#ical s!stem has and thus even the first
assimilation state of poison break down into their basal components is alread! varied.

2an! animals bleed from their orifices, whilst under#oin# or#an dama#es and a host of
other extremel! excruciatin# health ailments before finall! d!in# off in these test, half
mi#ht also be severel! poisoned b! the time the other half dies off, the test is too
imprecise and overlooks too man! factors to be even considered safe as a toxin test
indicator to even use as a species specific #au#e.

3ith the advances in modern da! science, cell and or#an cultures are now the normal
practice. he! can be convenientl! carried out ver! accuratel! in human cell lines whereb!
results are visible in real times, with ever! sin#le molecular interaction clearl! locatable,
testable and known. he ld50 test is totall! redundant as it lacks clarit!, precision or
clearl! identified molecular outcomes that cell culture can provide. 4uman cell lines would
#ive a much more accurate test, it is also faster to do and increases both the precision,
accurac!, effectivit! and efficienc! of toxin testin#s. 5ffects of toxins can be clearl!
elucidated this wa! alon# with clinical and hospital data from poisoned victim cases.

6ell cultures in human cell lines will be a clear cut indicator if humans will suffer if the!
took somethin# unknown or deemed safe or unsafe b! the ld50 test, as such testin# in a
different species is .ust non essential. his can be further proven b! some #enerali+ed
testin#s which has shown that most toxicit! testin#s done upon animals !ield inaccuracies
of between 758 9 :08 when compared to the normal human toxic dosa#es.
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