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

Explo Med. 2025;6:1001280 | h ps://doi.o g/10.37349/emed.2025.1001280 Page 1 © The Au ho (s) 2025. This is an Open Access a icle licensed unde a C ea i e Commons A ibu ion 4.0 In e na ional License (h ps://c ea i ecommons.o g/licenses/by/4.0/), which pe mi s un es ic ed use, sha ing, adap a ion, dis ibu ion and ep oduc ion in any medium o o ma , o any pu pose, e en comme cially, as long as you gi e app op ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he C ea i e Commons license, and indica e i changes we e made. 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. Publishe ’s no e Open Explo a ion main ains a neu al s ance on ju isdic ional claims in published ins i u ional a ilia ions and maps. All opinions exp essed in his a icle a e he pe sonal iews o he au ho (s) and do no ep esen he s ance o he edi o ial eam o he publishe . Re e ences Same JM, Chiu WA, Cogliano V, Jino J, K iebel D, Lunn RM, e al. The IARC Monog aphs: Upda ed P ocedu es o Mode n and T anspa en E idence Syn hesis in Cance Haza d Iden i ica ion. J Na l Cance Ins . 2020;112:30–7. [DOI] [PubMed] [PMC] 1. Baan RA, S ai K. The Monog aphs P og amme o he In e na ional Agency o Resea ch on Cance . A b ie his o y o i s P eamble. ALTEX. 2022;39:443–50. [DOI] [PubMed] 2. Schubaue -Be igan MK. In i ed Pe spec i e: Good Measu e-Assessing he Impac o Cance Haza d Iden i ica ion on Policies o Cance P e en ion. En i on Heal h Pe spec . 2023;131:121302. [DOI] [PubMed] [PMC] 3. 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