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Misleading nomenclature in the IARC Monographs Programme: a straightforward solution to improve accuracy and clarity

Author: López Lázaro, Miguel
Publisher: Open Exploration Publishing
Year: 2025
DOI: 10.37349/emed.2025.1001280
Source: https://idus.us.es/bitstreams/8c56a3a1-7da9-4f14-b3e3-8753d11a2068/download
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Explo a ion o Medicine
Open Access Pe spec i e
Misleading nomencla u e in he IARC Monog aphs P og amme: a
s aigh o wa d solu ion o imp o e accu acy and cla i y
Miguel López-Láza o*
Depa men o Pha macology, Facul y o Pha macy, Uni e si y o Se ille, 41012 Se illa, Spain
*Co espondence: Miguel López-Láza o, Depa men o Pha macology, Facul y o Pha macy, Uni e si y o Se ille, 41012
Se illa, Spain. [email p o ec ed]
Academic Edi o : Alessand o O aiano, Is i u o Nazionale Tumo i di Napoli, IRCCS “G. Pascale”, I aly
Recei ed: No embe 12, 2024 Accep ed: Janua y 17, 2025 Published: Feb ua y 7, 2025
Ci e his a icle: López-Láza o M. Misleading nomencla u e in he IARC Monog aphs P og amme: a s aigh o wa d solu ion
o imp o e accu acy and cla i y. Explo Med. 2025;6:1001280. h ps://doi.o g/10.37349/emed.2025.1001280
Abs ac
The In e na ional Agency o Resea ch on Cance (IARC) Monog aphs P og amme plays an impo an ole
in cance p e en ion by iden i ying po en ial ca cinogenic haza ds. Howe e , he e minology used in
IARC’s classi ica ions and Monog aphs can con use he public, heal h p o essionals, and policymake s.
Te ms like “ca cinogenic o humans” imply causa ion, al hough classi ica ions only indica e inc eased isk
unde ce ain condi ions. Fo example, he li e ime incidence o meso helioma among i e igh e s is
app oxima ely 14 in 10,000, compa ed o 7 in 10,000 in he gene al popula ion. Despi e doubling he isk,
occupa ional exposu e as a i e igh e does no cause his ype o cance in 9,986 ou o 10,000 i e igh e s.
Howe e , he IARC concludes ha “occupa ional exposu e as a i e igh e causes meso helioma” (IARC
Wo king G oup on he Iden i ica ion o Ca cinogenic Haza ds o Humans. Occupa ional Exposu e as a
Fi e igh e . Lyon: IARC; 2023. pp. 1–730. PMID: 37963216). In addi ion, he lack o essen ial in o ma ion
abou dosage and con ex in he IARC ca cinogen lis s can lead o agen s wi h heal h bene i s unde ce ain
condi ions (e.g., sola adia ion, ed mea consump ion, app o ed d ugs) being pe cei ed as uni e sally
ha m ul, discou aging bene icial exposu es, beha io s, o ea men s. He e, I p opose enaming he g oups
o agen s classi ied by he IARC and adding basic labels o speci ic agen s o imp o e he accu acy and
in e p e abili y o he IARC classi ica ion lis s. These adjus men s do no in e e e wi h he IARC’s objec i e
o iden i ying po en ial haza ds, a e easy o implemen , and enhance accu acy and cla i y, p o iding
s onge suppo o guide cance p e en ion s a egies.
Keywo ds
In e na ional Agency o Resea ch on Cance , IARC classi ica ion, IARC g oups, IARC lis , ca cinogen,
ca cinogenesis
In oduc ion
The Monog aphs P og amme o he In e na ional Agency o Resea ch on Cance (IARC), a b anch o he
Wo ld Heal h O ganiza ion (WHO), plays a key ole in cance p e en ion by iden i ying po en ial
Explo Med. 2025;6:1001280 | h ps://doi.o g/10.37349/emed.2025.1001280 Page 2
ca cinogenic haza ds. Al hough IARC does no make policy ecommenda ions, i s classi ica ions ha e a
signi ican global impac , o en in luencing egula ions and policies. Go e nmen s wo ldwide ely on IARC
cance classi ica ions o de elop a wide ange o egula ions, such as communica ing cance haza ds, se ing
moni o ing and epo ing equi emen s, imposing usage es ic ions, and es ablishing exposu e limi s o
ca cinogens [1–3]. Fo example, in 2009, he IARC Monog aphs P og amme classi ied he use o UV-
emi ing anning de ices in G oup 1 (ca cinogenic o humans). A e his classi ica ion, es ic ions o bans
on hese de ices we e ecommended o implemen ed, and a me a-analysis showed ha he global use o
indoo anning signi ican ly dec eased ollowing hese es ic ions [4]. This example shows how iden i ying
haza ds can encou age ac ions o p e en cance [3].
As s a ed in i s p eamble, he IARC Monog aphs ocus on iden i ying po en ial ca cinogenic haza ds,
no on assessing he ac ual isk o cance in exposed indi iduals. A ca cinogenic haza d e e s o an agen
capable o causing cance unde speci ic condi ions, while cance isk measu es he likelihood o cance
occu ing a a speci ic le el o exposu e. The Monog aphs assess he s eng h o he e idence ha an agen
is a ca cinogenic haza d unde speci ic condi ions, p o iding he i s s ep in unde s anding po en ial isks
associa ed wi h ce ain agen s [1, 2, 5].
In isk assessmen , he e a e ou main s eps: haza d iden i ica ion, dose- esponse assessmen ,
exposu e assessmen , and isk cha ac e iza ion. The IARC Monog aphs ocus on haza d iden i ica ion. This
is an essen ial s ep bu does no o e a comple e isk assessmen . Al hough he Monog aphs ha e been
c i icized o no pe o ming all ou s eps [6], hei objec i e is o iden i y haza ds and encou age
egula o y bodies o conduc he ull isk assessmen s ha guide speci ic policies and p o ec ions, a ask
beyond he scope o he Monog aphs P og amme [7].
Howe e , ocusing on iden i ying po en ial haza ds wi hou unde aking a comple e isk assessmen
can lead o con usion and conce n i he indings a e no p esen ed accu a ely and clea ly. Fo example,
some agen s p o ide heal h bene i s a mode a e exposu es bu may become ha m ul a highe exposu es.
Since he Monog aphs iden i y agen s ha can po en ially cause cance unde ce ain, some imes
uncommon, condi ions, bene icial agen s a no mal exposu es can be classi ied as ca cinogenic o humans
unde he IARC p o ocol. I dosage and con ex a e no clea ly speci ied, labeling hese agen s as
ca cinogenic o humans can con use he public, heal h p o essionals, and policymake s [8].
The e minology used in he IARC classi ica ions is ano he sou ce o unnecessa y con usion and
conce n. The e m “ca cinogenic o humans” used o G oup 1 agen s implies an ine i abili y o cance
causa ion. E ymologically, ca cinogenic means “p oducing cance ” o “causing cance ”. Many dic iona ies
de ine ca cinogenic his way, which in luences how he gene al popula ion unde s ands he e m
“ca cinogenic o humans”. Fo ins ance, acco ding o he Ox o d English Dic iona y, ca cinogenic means
“ ha causes cance o induces he malignan ans o ma ion o cells”. Impo an ly, his li e al meaning is
also used in he inal e alua ion sec ion o all Monog aphs o agen s classi ied in G oup 1. Fo example,
acco ding o he IARC’s Monog aphs, “sola adia ion causes cu aneous malignan melanoma, squamous cell
ca cinoma o he skin and basal cell ca cinoma o he skin” [9], and “occupa ional exposu e as a i e igh e
causes meso helioma” [10]. These examples show ha he IARC Monog aphs o en use he e ms “causes
cance ” and “inc eases he isk o cance ” in e changeably.
The ollowing example may cla i y he dis inc ion be ween “causes cance ” and “inc eases he isk o
cance ”. Based on SEER Incidence Da a, 1975–2021, he li e ime incidence o meso helioma in he gene al
popula ion is app oxima ely 7 in 10,000 indi iduals. This es ima e de i es om an annual incidence a e o
abou 0.9 pe 100,000 people, which, accumula ed o e an a e age li espan o 80 yea s, yields a li e ime
isk o 0.072%. Fi e igh e s ha e abou wice he isk o meso helioma compa ed o he gene al popula ion
[11], esul ing in a li e ime incidence o app oxima ely 14 in 10,000 among i e igh e s. These da a indica e
ha , while being a i e igh e inc eases he isk o de eloping his cance , i does no cause i in 9,986 ou o
10,000 i e igh e s. Howe e , he IARC s a es ha “occupa ional exposu e as a i e igh e causes
meso helioma” [10]. I exposu e o an agen esul s in cance o 14 people bu no o 9,986 people, is i
accu a e o say ha exposu e o he agen causes cance ? Wouldn’ i be mo e p ecise o say ha exposu e
o he agen inc eases he isk o cance ?
Explo Med. 2025;6:1001280 | h ps://doi.o g/10.37349/emed.2025.1001280 Page 3
Using his inaccu a e and ala ming e minology migh help discou age exposu e o agen s ha a e
ha m ul in almos all scena ios, like obacco smoke. Howe e , he same e minology is also used o agen s
ha a e bene icial a ce ain doses o in speci ic con ex s. Fo example, excessi e exposu e o sola
adia ion inc eases he isk o skin cance , bu no mal sun exposu e is essen ial o p oducing i amin D,
which is i al o human heal h. When dose o con ex de e mines whe he an agen is bene icial o
ha m ul, labels like “ca cinogenic o humans” o “causes cance ” can mislead he public and discou age
bene icial beha io s, ul ima ely ha ming hei heal h. This misunde s anding has al eady occu ed. The ac
ha he IARC, he cance agency o he WHO, labels sola adia ion as “ca cinogenic o humans” has likely
led many people o a oid sunligh . Obse a ional s udies ha e shown ha a oiding sun exposu e is a isk
ac o o all-cause mo ali y [12]. A isk analysis o a p ospec i e s udy ound ha nonsmoke s who
a oided sun exposu e had a li e expec ancy simila o smoke s wi h high sun exposu e [13]. Compa ed o
hose wi h he highes sun exposu e, sun a oide s had a educed li e expec ancy o 0.6–2.1 yea s [13, 14].
The IARC a ely speci ies dose and con ex in i s lis o ca cinogens, e en hough hese ac o s a e
c ucial in de e mining ac ual cance isk. Fo example, while ed mea is classi ied as “p obably
ca cinogenic o humans” (G oup 2A), mode a e consump ion o e s high-quali y p o ein and essen ial
nu ien s such as B i amins, i on, and zinc. In egions wi h limi ed ood a ailabili y, ed mea may be a
di icul - o- eplace sou ce o hese nu ien s. Wi hou cla i ying he le el o consump ion a which ed mea
poses a isk, people migh a oid i en i ely, missing ou on i s heal h bene i s. Simila ly, se e al app o ed
d ugs a e classi ied as G oup 1 ca cinogens, e en hough hey a e s anda d ea men s o speci ic diseases
and o e signi ican heal h bene i s when used app op ia ely. These examples show ha imp ecise labels
ha lack dose and con ex may discou age bene icial beha io s, ea men s, o exposu es ha ha e posi i e
heal h e ec s.
The need o mo e accu a e e minology is e iden o a oid unnecessa y con usion and ensu e ha
people, heal h p o essionals, and policymake s make in o med decisions based on a clea unde s anding o
isk. The IARC ecognizes he need o imp o e communica ion o i s e alua ion esul s and has ecen ly
added use - iendly ea u es like “ equen ly asked ques ions” and in og aphics o explain i s classi ica ions
and he suppo ing e idence [7]. Howe e , he ongoing use o imp ecise e minology and he lack o
essen ial con ex , especially in he IARC’s classi ica ion lis o ca cinogens, will likely con inue o cause
con usion and conce n un il hese issues a e p ope ly add essed. This manusc ip p oposes a
s aigh o wa d solu ion o he IARC Monog aphs o enhance he accu acy and cla i y o i s
communica ions.
A s aigh o wa d solu ion o imp o e accu acy and p e en unnecessa y
con usion
The i s s ep o imp o e accu acy and p e en unnecessa y con usion is o ename he g oups o agen s
classi ied by he IARC Monog aphs. As shown in Table 1, G oup 1 (ca cinogenic o humans) could be
enamed as “agen s ha inc ease cance isk in humans”; G oup 2A (p obably ca cinogenic o humans) as
“agen s ha p obably inc ease cance isk in humans”; G oup 2B (possibly ca cinogenic o humans) as
“agen s ha possibly inc ease cance isk in humans”; and G oup 3 (no classi iable as o i s ca cinogenici y
o humans) as “agen s wi h insu icien o no e idence o cance isk in humans”.
Since IARC classi ica ions only indica e e idence o inc eased isk unde ce ain condi ions, hese new
g oup names emphasize cance isk a he han implying di ec causa ion. As shown in he i e igh e
example, he e m “inc eases cance isk” is mo e p ecise han “is ca cinogenic” o “causes cance ” and is
easie o mos people o unde s and, including heal h p o essionals and policymake s. The p oposed name
o G oup 3 e lec s IARC’s ecen me ging o wo ca ego ies: he o me G oup 3 (no classi iable as o i s
ca cinogenici y o humans) and he now-elimina ed G oup 4 (p obably no ca cinogenic o humans). This
change is impo an o cla i y ha no all agen s in his g oup a e suspec ed o inc easing cance isk.
The second s ep o imp o ing accu acy and educing unnecessa y con usion is o add concise labels o
speci ic agen s o p o ide essen ial con ex and minimize misin e p e a ion. A leas wo basic labels should
be used o speci ic agen s: “excessi e” o agen s whe e dose de e mines whe he he agen is bene icial o
Explo Med. 2025;6:1001280 | h ps://doi.o g/10.37349/emed.2025.1001280 Page 4
Table 1. P oposed classi ica ion sys em o imp o e accu acy and cla i y
Ca ego y Cu en classi ica ion sys em P oposed classi ica ion sys em
Ca cinogenic o humans Agen s ha inc ease cance isk in humansG oup 1
Tobacco smoke, plu onium, occupa ional
exposu e as a i e igh e , sola adia ion,
e oposide, e c.
Tobacco smoke, plu onium, occupa ional exposu e as a
i e igh e , excessi e sola adia ion, e oposide
(bene icial unde ce ain condi ions), e c.
P obably ca cinogenic o humans Agen s ha p obably inc ease cance isk in humansG oup 2A
Consump ion o ed mea , ac olein, mala hion,
e c.
Excessi e consump ion o ed mea , ac olein,
mala hion, e c.
Possibly ca cinogenic o humans Agen s ha possibly inc ease cance isk in humansG oup 2B
Radio equency elec omagne ic ields,
aspa ame, digoxin, e c.
Radio equency elec omagne ic ields, aspa ame,
digoxin (bene icial unde ce ain condi ions), e c.
No classi iable as o i s ca cinogenici y o
humans
Agen s wi h insu icien o no e idence o cance isk in
humans
G oup 3
Diazepam, co ee d inking, ea, e c. Diazepam, co ee d inking, ea, e c.
Cu en and p oposed classi ica ion sys em o agen s e alua ed in he In e na ional Agency o Resea ch on Cance (IARC)
Monog aphs, wi h examples p o ided in each g oup o show how speci ic agen s could be labeled
ha m ul, and “(bene icial unde ce ain condi ions)” o agen s whe e con ex de e mines whe he he
agen is bene icial o ha m ul. Fo agen s whe e dose and con ex do no o e any heal h bene i s, such as
obacco smoke o occupa ional exposu e as a i e igh e , no labels a e necessa y (Table 1).
The label “excessi e” could p ecede agen s ha a e bene icial a mode a e exposu es (e.g., sola
adia ion, ed mea consump ion) o cla i y ha mode a e exposu e can ha e heal h bene i s. In con as ,
he label “excessi e” would be unnecessa y o agen s lacking demons a ed heal h bene i s a mode a e
exposu es o ha can be easily subs i u ed, such as aspa ame. While aspa ame and o he agen s on he
IARC lis s migh pose cance isks only a high doses, enaming he g oups as shown in Table 1 would be
su icien o help p e en misleading headlines like “Aspa ame is a possible ca cinogen” [15]. The exis ence
o such headlines, e en in espec ed scien i ic jou nals, sugges s ha he cu en IARC g oup names can be
misin e p e ed e en by scien is s [15].
The label “(bene icial unde ce ain condi ions)” could apply o agen s ha , a no mal exposu e le els,
p o ide heal h bene i s in speci ic con ex s despi e po en ial cance isks a he same exposu e le els.
Examples include app o ed d ugs like e oposide o digoxin. Adding his basic con ex would help people
unde s and ha ce ain agen s o e heal h bene i s while ca ying a po en ial cance isk. Wi hou hese
cla i ica ions, he IARC lis s migh unin en ionally discou age he use o essen ial ea men s; o example,
e oposide and digoxin a e ac ually included in he WHO Model Lis o Essen ial Medicines (23 d lis , 2023)
[16].
Conclusions
In conclusion, he changes p oposed in his manusc ip o e a s aigh o wa d and e ec i e solu ion o he
IARC Monog aphs P og amme o enhance bo h he accu acy and cla i y o i s scien i ic communica ions. By
upda ing he classi ica ion language om “ca cinogenic o humans” o mo e p ecise e ms like “agen s ha
inc ease cance isk in humans”, he p oposed sys em educes he likelihood o misin e p e a ion while
p ese ing he IARC’s ocus on iden i ying po en ial haza ds wi hou conduc ing ull isk assessmen s. Since
“ca cinogenic haza ds o humans” can be de ined as “agen s ha inc ease cance isk in humans”, he
cu en i le, IARC Monog aphs on he Iden i ica ion o Ca cinogenic Haza ds o Humans, emains ully
consis en wi h he p oposed g oup names in Table 1. Addi ionally, adding con ex -sensi i e labels, such as
“excessi e” o “(bene icial unde ce ain condi ions)”, p o ides essen ial con ex o agen s ha o e heal h
bene i s a mode a e exposu e le els o in speci ic si ua ions. These adjus men s nei he al e he IARC’s
ounda ional mission no equi e signi ican changes, ye hey would imp o e cla i y, enhance accu acy,
and p o ide s onge suppo o cance p e en ion s a egies.
Explo Med. 2025;6:1001280 | h ps://doi.o g/10.37349/emed.2025.1001280 Page 5
Abb e ia ions
IARC: In e na ional Agency o Resea ch on Cance
WHO: Wo ld Heal h O ganiza ion
Decla a ions
Acknowledgmen s
The au ho acknowledges his esea ch eam o help ul discussions.
Au ho con ibu ions
MLL: Concep ualiza ion, In es iga ion, W i ing—o iginal d a , W i ing— e iew & edi ing.
Con lic s o in e es
The au ho decla es no con lic o in e es .
E hical app o al
No applicable.
Consen o pa icipa e
No applicable.
Consen o publica ion
No applicable.
A ailabili y o da a and ma e ials
No applicable.
Funding
No applicable.
Copy igh
© The Au ho (s) 2025.
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ep esen he s ance o he edi o ial eam o he publishe .
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