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Advisory Group recommendations on priorities for the IARC Monographs

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... Merkel cell polyoma virus (MCV) is classified as "probably carcinogenic to humans" (Group 2A); BK virus and JC virus are classified as "possibly carcinogenic to humans" (Group 2B); SV40 virus is regarded as "not classifiable as to its carcinogenicity to humans"(Group 3) [11]. Recently, evidence for the carcinogenicity of MCV has accumulated [12]. 1 The details of Baltimore system are found in refs. [13,14]. ...
... In addition, a specific CMV strain has been reported to transform human mammary epithelial cells into triplenegative breast cancer-like cells [329]. Consistent with these findings, the IARC advisory board group recently recommended CMV as a high priority agent to be evaluated for its carcinogenicity [12]. ...
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Cancer arises from the accumulation of genetic and epigenetic alterations. Even in the era of precision oncology, carcinogens contributing to neoplastic process are still an important focus of research. Comprehensive genomic analyses have revealed various combinations of base substitutions, referred to as the mutational signatures, in cancer. Each mutational signature is believed to arise from specific DNA damage and repair processes, including carcinogens. However, as a type of carcinogen, tumor viruses increase the cancer risk by alternative mechanisms, including insertional mutagenesis, viral oncogenes, and immunosuppression. In this review, we summarize virus-driven carcinogenesis to provide a framework for the control of malignant cell proliferation. We first provide a brief overview of oncogenic viruses and describe their implication in virus-related tumors. Next, we describe tumor viruses (HPV, Human papilloma virus; HBV, Hepatitis B virus; HCV, Hepatitis C virus; EBV, Epstein–Barr virus; Kaposi sarcoma herpesvirus; MCV, Merkel cell polyoma virus; HTLV-1, Human T-cell lymphotropic virus, type-1) and tumor virus-related cancers. Lastly, we introduce emerging tumor virus candidates, human cytomegalovirus (CMV), human herpesvirus-6 (HHV-6) and adeno-associated virus-2 (AAV-2). We expect this review to be a hub in a complex network of data for virus-associated carcinogenesis.
... Although their use has been progressively limited and banned in Europe during the 90 s, due to their resistance to degradation, PBDE and PBB are widespread in the environment [1]. The long-term toxic effects of PBDE and PBB in humans are not completely elucidated, but they are known to have endocrine disrupting properties and in 2019 PBDE have been included in the high-priority list of agents not previously evaluated by the International Agency for Research on Cancer (IARC) Monographs based on relevant bioassay and mechanistic studies [2,3]. ...
... PFAS are characterized by long half-lives in the biota and humans and biomonitoring studies have suggested that PFOA and PFOS, the two main PFAS representatives, are ubiquitously present in the blood of humans worldwide [5]. PFAS are strongly suspected to act as endocrine disrupting chemicals (EDCs), and PFOA has been classified by the IARC as "possibly carcinogenic to humans" (Group 2B) [3,6]. ...
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Background Brominated flame retardants (BFR) and per- and polyfluorinated alkylated substances (PFAS) are two groups of substances suspected to act as endocrine disruptors. Such substances could therefore be implicated in the occurrence of breast cancer, nevertheless, previous studies have led to inconstant results. Due to the large correlation between these substances, and the possibly non-linear effects they exert, evaluating their joint impact as mixtures on health remains challenging. This exploratory study aimed to generate hypotheses on the relationship between circulating levels of 7 BFR (6 polybrominated diphenyl ethers and 1 polybrominated biphenyls) and 11 PFAS and the risk of breast cancer in a case–control study nested in the E3N French prospective cohort by performing two methods: Principal Component Regression (PCR) models, and Bayesian Kernel Machine Regression (BKMR) models. Methods 194 post-menopausal breast cancer cases and 194 controls were included in the present study. Circulating levels of BFR and PFAS were measured by gas chromatography coupled to high-resolution mass spectrometry and liquid chromatography coupled to tandem mass spectrometry, respectively. The first statistical approach was based on Principal Component Analysis (PCA) followed by logistic regression models that included the identified principal components as main exposure variables. The second approach used BKMR models with hierarchical variable selection, this latter being suitable for highly correlated exposures. Both approaches were also run separately for Estrogen Receptor positive (ER +) and Estrogen Receptor negative (ER-) breast cancer cases. Results PCA identified four principal components accounting for 67% of the total variance. Component 3 showed a marginal association with ER + breast cancer risk. No clear association between BFR and PFAS mixtures and breast cancer was identified using BKMR models, and the credible intervals obtained were very wide. Finally, the BKMR models suggested a negative cumulative effect of BFR and PFAS on ER- breast cancer risk, and a positive cumulative effect on ER + breast cancer risk. Conclusion Although globally no clear association was identified, both approaches suggested a differential effect of BFR and PFAS mixtures on ER + and ER- breast cancer risk. However, the results for ER- breast cancer should be interpreted carefully due to the small number of ER- cases included in the study. Further studies evaluating mixtures of substances on larger study populations are needed.
... Aflatoxins such as AFB1, AFB2, AFG1, AFG2, and AFM1 are characterized as Group 1 carcinogens [85,86]. According to the IARC report, aflatoxins are annotated as mediumpriority agents with possible consideration for future evaluation regarding additional sites of cancer [176]. Several studies have confirmed the link between aflatoxins and increased risk of hepatic cancer. ...
... A bioassay in rats reported FB1 hepatotoxicity and hepato-carcinogenicity [187]. There is a recommendation for a high evaluation priority for FB1 due to substantial emerging information after the previous evaluation by the IARC Monographs [176]. There is evidence for ceramide synthase inhibition in individuals who consumed corn-based foods high in FB1 [188]. ...
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Mycotoxins are well established toxic metabolic entities produced when fungi invade agricultural/farm produce, and this happens especially when the conditions are favourable. Exposure to mycotoxins can directly take place via the consumption of infected foods and feeds; humans can also be indirectly exposed from consuming animals fed with infected feeds. Among the hundreds of mycotoxins known to humans, around a handful have drawn the most concern because of their occurrence in food and severe effects on human health. The increasing public health importance of mycotoxins across human and livestock environments mandates the continued review of the relevant literature, especially with regard to understanding their toxicological mechanisms. In particular, our analysis of recently conducted reviews showed that the toxicological mechanisms of mycotoxins deserve additional attention to help provide enhanced understanding regarding this subject matter. For this reason, this current work reviewed the mycotoxins’ toxicological mechanisms involving humans, livestock, and their associated health concerns. In particular, we have deepened our understanding about how the mycotoxins’ toxicological mechanisms impact on the human cellular genome. Along with the significance of mycotoxin toxicities and their toxicological mechanisms, there are associated health concerns arising from exposures to these toxins, including DNA damage, kidney damage, DNA/RNA mutations, growth impairment in children, gene modifications, and immune impairment. More needs to be done to enhance the understanding regards the mechanisms underscoring the environmental implications of mycotoxins, which can be actualized via risk assessment studies into the conditions/factors facilitating mycotoxins’ toxicities.
... The publication of the revised Preamble is very timely, as an expert panel recently convened by the IARC Monograph program recommended review of a broad range of old and new agents in the next five years (3,4). The expert panel considered more than 170 unique candidate agents nominated by the scientific community and general public, and those agents recommended for review are wide ranging, including breast implants, cannabis smoking, e-cigarettes, and disinfection by-products. ...
... In conclusion, according to NTP, there is now clear evidence that RFR causes cancer in experimental animals. RFR re-evaluation has also been listed as a priority by IARC [87]. There is also stronger evidence that RFR exposure is responsible for causing alteration of various sperm parameters, thus, affecting male fertility. ...
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The proliferation of cellular antennas and other radiofrequency radiation (RFR) generating devices of the last decades has led to more and more concerns about the potential health effects from RFR exposure. Since the 2011 classification as a probable carcinogen by the International Agency for Research on Cancer (IARC), more experimental studies have been published that support a causal association between RFR exposure and health hazards. As regard cancer risk, two long-term experimental studies have been recently published by the US National Toxicology Program (NTP) and the Italian Ramazzini Institute (RI). Despite important experimental differences, both studies found statistically significant increases in the development of the same type of very rare glial malignant tumors. In addition to carcinogenicity, reproductive organs might be particularly exposed, as well as sensitive to RFR. In this work, we reviewed the currently available evidence from in vivo studies on carcinogenicity and reproductive toxicity studies in order to summarize the contribution of experimental research to the prevention of the adverse effects of RFR on human health.
... Some studies suggest that RF exposure can cause cancer, and thus the International Agency for Research on Cancer classified RF EMF as a "possibly carcinogenic to humans" (Group 2B) [3]. In a recent recommendation of a periodically working Advisory Group for IARC "to ensure that the Monographs evaluations reflect the current state of scientific evidence relevant to carcinogenicity" the group recommended radiofrequency exposure (among others) for re-evaluation "with high priority" [6]. There is further no scientific support for that e↵ects on other health parameters occur at exposure levels that are below exposure guideline levels, even though some research groups have published non-carcinogen related findings after RF exposure at such levels (see [4,5]). ...
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The introduction of the fifth generation (5G) of wireless communication will increase the number of high-frequency-powered base stations and other devices. The question is if such higher frequencies (in this review, 6–100 GHz, millimeter waves, MMW) can have a health impact. This review analyzed 94 relevant publications performing in vivo or in vitro investigations. Each study was characterized for: study type (in vivo, in vitro), biological material (species, cell type, etc.), biological endpoint, exposure (frequency, exposure duration, power density), results, and certain quality criteria. Eighty percent of the in vivo studies showed responses to exposure, while 58% of the in vitro studies demonstrated effects. The responses affected all biological endpoints studied. There was no consistent relationship between power density, exposure duration, or frequency, and exposure effects. The available studies do not provide adequate and sufficient information for a meaningful safety assessment, or for the question about non-thermal effects. There is a need for research regarding local heat developments on small surfaces, e.g., skin or the eye, and on any environmental impact. Our quality analysis shows that for future studies to be useful for safety assessment, design and implementation need to be significantly improved.
... We present a fraction of the available scientific evidence to demonstrate that their categorisation is false. This is an important communication because the International Agency for Research on Cancer (IARC) has recently announced reevaluation of some of these as 'high priority' [2]. ...
... Other infectious pathogens for which evidence on causality is strengthening might be included in future estimates. These include Salmonella typhi as a cause of gallbladder cancer, malaria (Plasmodium species) as a cause of Burkitt lymphoma, Merkel cell virus causing Merkel cell carcinoma, 25 HCV causing cholangiocarcinoma, 26 and Epstein-Barr virus contributing to non-Hodgkin lymphoma and gastric cancer. ...
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Background: Infectious pathogens are strong and modifiable causes of cancer. The aim of this study was to improve estimates of the global and regional burden of infection-attributable cancers to inform research priorities and facilitate prevention efforts. Methods: We used the GLOBOCAN 2018 database of cancer incidence and mortality rates and estimated the attributable fractions and global incidence for specific anatomical cancer sites, subsites, or histological subtypes known to be associated with ten infectious pathogens classified as human carcinogens. We calculated absolute numbers and age-standardised incidence rates (ASIR) of infection-attributable cancers at the country level. Estimates were stratified for sex, age group, and country, and were aggregated according to geographical regions and World Bank income groups. Findings: We found that, for 2018, an estimated 2·2 million infection-attributable cancer cases were diagnosed worldwide, corresponding to an infection-attributable ASIR of 25·0 cases per 100 000 person-years. Primary causes were Helicobacter pylori (810 000 cases, ASIR 8·7 cases per 100 000 person-years), human papillomavirus (690 000, 8·0), hepatitis B virus (360 000, 4·1) and hepatitis C virus (160 000, 1·7). Infection-attributable ASIR was highest in eastern Asia (37·9 cases per 100 000 person-years) and sub-Saharan Africa (33·1), and lowest in northern Europe (13·6) and western Asia (13·8). China accounted for a third of worldwide cancer cases attributable to infection, driven by high ASIR of H pylori (15·6) and hepatitis B virus (11·7) infection. The cancer burden attributed to human papillomavirus showed the clearest relationship with country income level (from ASIR of 6·9 cases per 100 000 person-years in high-income countries to 16·1 in low-income countries). Interpretation: Infection-attributable cancer incidence, in addition to the absolute number of cases, allows for refined geographic analyses and identification of populations with a high infection-associated cancer burden. When cancer prevention is largely considered in a non-communicable disease context, there is a crucial need for resources directed towards cancer prevention programmes that target infection, particularly in high-risk populations. Such interventions can markedly reduce the increasing cancer burden and associated mortality. Funding: International Agency for Research on Cancer.
... Since 2016, the use of single-wall carbon nanotubes is guided by the European Union's Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulations [11]. Carbon nanotubes are high on the priority list for IARC monographs [12]. So far, one category of carbon nanotubes (MWCNT-7) [13]was classified as possibly carcinogenic to humans (IARC Group 2B) but it is evident that world-wide preventive measures have not yet been considered or taken. ...
... Considering that the majority of cases were diagnosed in patients with textured implants, the evidence linking BIA-ALCL to this type of implant surface has raised concerns about the long-term safety of these devices. In this context, breast implants have been inserted in the list of agents with high priority for evaluation by the International Agency for Research on Cancer (IARC) for the inclusion in the monographs of carcinogenic risks to humans [3]. ...
Article
Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized non-Hodgkin lymphoma of T-cell origin. Despite the low incidence of this new disease, the increasing use of breast implants for cosmetic or post-mastectomy reconstruction purposes places BIA-ALC as an emerging and compelling medical challenge. The real BIA-ALCL pathogenesis has not been fully uncovered so far, while different putative causal factors have been proposed. Breast implants with textured surfaces seem to be associated with nearly all cases of BIA-ALCL, while the real the risk of disease development has not been well estimated so far. Late onset, persistent seroma around breast implant represents the classical clinical presentation. Most of the BIA-ALCL patients presents with localized disease, which confers an excellent prognosis. Unlike other non-Hodgkin lymphomas, surgical excision of the mass has a key role in the treatment. For patients with advanced and disseminated diseases, the treatment did not differ from other types of T-cell lymphoma. For these reasons, BIA-ALCL represents an emerging disease which requires multidisciplinary team approach to well define diagnostic workup and treatment for each patient. This review article aims to summarize available data on BIA-ALCL. First, we will outline available data on BIA-ALCL epidemiology, pathogenesis, diagnostic work-up, and treatment. Second, we will point out the potential psychological implications as well as the risk of perception distortion for women with breast implants, especially for those with previous breast cancer. Lastly, we will summarize the current national recommendations regarding textured breast implants and discuss the diagnostic-therapeutic algorithm for BIA-ALCL management.
... Additionally, the U.S. Environmental Protection Agency (EPA) classified PFOA as well as two other PFAS, perfluoroctosulfonate (PFOS) and GenX, as having suggestive evidence of carcinogenic potential [2][3][4]. 6-Induces chronic inflammation Elevated white blood cells, myeloperoxidase activity, altered cytokine and/or chemokine production 7-Is immunosuppressive Decreased immunosurveillance, immune system dysfunction 8-Modulates receptor-mediated effects Receptor in/activation (e.g., ER, PPAR, AhR) or modulation of endogenous ligands (including hormones) 9-Causes immortalization Inhibition of senescence, cell transformation 10-Alters cell proliferation, cell death or nutrient supply Increased proliferation, decreased apoptosis, changes in growth factors, energetics and signaling pathways related to cellular replication or cell-cycle control, angiogenesis Incorporation of a key characteristic analysis into risk assessments is increasingly utilized by U.S. and international government agencies including IARC [8], the Integrative Risk Information System at the U.S. EPA [9], the National Toxicology Program [7] and California's Office of Environmental Health Hazard Assessment [10]. "Some perfluorinated chemicals" were also listed as a priority for IARC to review in the coming years [11]. ...
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Per- and polyfluoroalkyl substances (PFAS) constitute a large class of environmentally persistent chemicals used in industrial and consumer products. Human exposure to PFAS is extensive, and PFAS contamination has been reported in drinking water and food supplies as well as in the serum of nearly all people. The most well-studied member of the PFAS class, perfluorooctanoic acid (PFOA), induces tumors in animal bioassays and has been associated with elevated risk of cancer in human populations. GenX, one of the PFOA replacement chemicals, induces tumors in animal bioassays as well. Using the Key Characteristics of Carcinogens framework for cancer hazard identification, we considered the existing epidemiological, toxicological and mechanistic data for 26 different PFAS. We found strong evidence that multiple PFAS induce oxidative stress, are immunosuppressive, and modulate receptor-mediated effects. We also found suggestive evidence indicating that some PFAS can induce epigenetic alterations and influence cell proliferation. Experimental data indicate that PFAS are not genotoxic and generally do not undergo metabolic activation. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. While more research is needed to address data gaps, evidence exists that several PFAS exhibit one or more of the key characteristics of carcinogens.
... Unfortunately, the long-term toxic effects of these BFRs in humans are not completely known, although they are suspected to act as EDCs, since a link between exposure to BFRs and several endocrine-related diseases has been reported [11]. In 2019, PBDEs, one of the major groups of BFRs, have been included in the high-priority list of agents not previously evaluated by the International Agency for Research on Cancer (IARC) Monographs on the basis of relevant bioassay and mechanistic evidence [12]. ...
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Background: Brominated flame retardants (BFRs) are lipophilic substances with endocrine-disrupting properties. To date, only few investigations, mainly retrospective case-control studies, have explored the link between internal levels of BFRs and the risk of breast cancer, leading to conflicting results. We investigated the associations between plasma concentrations of two main groups of BFRs, PBDEs (pentabromodiphenyl ethers) and PBBs (polybrominated biphenyls), and the risk of breast cancer in a nested case-control study. Methods: A total of 197 incident breast cancer cases and 197 controls with a blood sample collected in 1994-1999 were included. Plasma levels of PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE153, BDE-154) and of PBB-153 were measured by gas chromatography coupled to high-resolution mass spectrometry. Conditional logistic regression models, adjusted for potential confounders, were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Women were aged 56 years on average at blood draw. All cases, except for one, were diagnosed after menopause, with an average age at diagnosis of 68 years. Overall, we found no evidence of an association between plasma levels of PBDEs and PBB-153 and postmenopausal breast cancer risk (log-concentrations of BFRs yielding non-statistically significant ORs of 0.87 to 1.07). The analysis showed a non-linear inverse association for BDE-100 and BDE-153 and postmenopausal breast cancer risk; nevertheless, these findings were statistically significant only when the exposure was modeled as ng/L plasma (third vs. first quintile: OR = 0.42, 95%CI = 0.19-0.93 and OR = 0.42, 95%CI = 0.18-0.98, respectively) and not when modeled as ng/gr of lipids (OR = 0.58, 95%CI = 0.27-1.25 and OR = 0.53, 95%CI = 0.25-1.17). These results were unchanged in stratified analyses by tumor hormone receptor expression or body mass index. Conclusions: Our results suggest no clear association between internal levels of PBDEs and PBB-153 and the risk of breast cancer in postmenopausal women. However, these findings need to be carefully interpreted, taking into account limitations due to the limited number of women included in the study, the lack of information concerning genetic susceptibility of cases, and the unavailability of exposure assessment during critical windows of susceptibility for breast cancer. More studies are warranted to further investigate the relationships between PBDE and PBB exposure and breast cancer risk.
... Based on evaluation of the available literature including experimental animal studies and epidemiological studies in humans, in 2011, the World Health Organization (WHO)/International Agency for Research on Cancer (IARC) classified radiofrequency electromagnetic fields (RF-EMFs) associated with cellular phone use as possibly carcinogenic to humans [7]. Recently, an advisory group of 29 scientists recommended that IARC prioritize a new review of the carcinogenicity of RF-EMF by 2024 due to mechanistic evidence of the carcinogenicity of cell phone radiation published since 2011 [8]. ...
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We investigated whether cellular phone use was associated with increased risk of tumors using a meta-analysis of case-control studies. PubMed and EMBASE were searched from inception to July 2018. The primary outcome was the risk of tumors by cellular phone use, which was measured by pooling each odds ratio (OR) and its 95% confidence interval (CI). In a meta-analysis of 46 case-control studies, compared with never or rarely having used a cellular phone, regular use was not associated with tumor risk in the random-effects meta-analysis. However, in the subgroup meta-analysis by research group, there was a statistically significant positive association (harmful effect) in the Hardell et al. studies (OR, 1.15-95% CI, 1.00 to 1.33-n = 10), a statistically significant negative association (beneficial effect) in the INTERPHONE-related studies (case-control studies from 13 countries coordinated by the International Agency for Research on Cancer (IARC); (OR, 0.81-95% CI, 0.75 to 0.89-n = 9), and no statistically significant association in other research groups' studies. Further, cellular phone use with cumulative call time more than 1000 h statistically significantly increased the risk of tumors. This comprehensive meta-analysis of case-control studies found evidence that linked cellular phone use to increased tumor risk.
... Poor oral hygiene has not been evaluated by the IARC monographs as to its carcinogenicity in humans but has recently been recommended among the priorities for future evaluation. 30 In the present study, data on three integral setting-relevant features were collected. These were frequency of tooth cleaning, cleaning implement (discussed separately below due to its different hypothesized biological mechanisms) and use of charcoal when cleaning teeth. ...
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In the African esophageal squamous cell carcinoma (ESCC) corridor, recent work from Kenya found increased ESCC risk associated with poor oral health, including an ill‐understood association with dental fluorosis. We examined these associations in a Tanzanian study, which included examination of potential biases influencing the latter association. This age and sex frequency‐matched case‐control study included 310 ESCC cases and 313 hospital visitor/patient controls. Exposures included self‐reported oral hygiene and nondental observer assessed decayed+missing+filled tooth count (DMFT index) and the Thylstrup‐Fejerskov dental fluorosis index (TFI). Blind to this nondental observer TFI, a dentist independently assessed fluorosis on photographs of 75 participants. Odds ratios (ORs) are adjusted for demographic factors, alcohol and tobacco. ESCC risk was associated with using a chewed stick to brush teeth (OR 2.3 [95% CI: 1.3‐4.1]), using charcoal to whiten teeth (OR 2.13 [95% CI: 1.3, 4.1]) and linearly with the DMFT index (OR 3.3 95% CI: [1.8, 6.0] for ≥10 vs 0). Nondental observer‐assessed fluorosis was strongly associated with ESCC risk (OR 13.5 [95% CI: 5.7‐31.9] for TFI 5+ v 0). However, the professional dentist's assessment indicated that only 43% (10/23) of participants assessed as TFI 5+ actually had fluorosis. In summary, using oral charcoal, brushing with a chewed stick and missing/decayed teeth may be risk factors for ESCC in Tanzania, for which dose‐response and mechanistic research is needed. Links of ESCC with “dental fluorosis” suffered from severe exposure misclassification, rendering it impossible to disentangle any effects of fluorosis, extrinsic staining or reverse causality.
... However, an international group of experts raised issues on the consequences on the innovation development of this "scientifically unjustified proposal" [3,76]. The authors also claimed that the proposal of re-evaluation asked by the IARC Advisory Group is still pending [77,78]. ...
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Carbon nanotubes (CNTs) and carbon nanofibers (CNFs) are erroneously considered as singular material entities. Instead, they should be regarded as a heterogeneous class of materials bearing different properties eliciting peculiar biological outcomes both in vitro and in vivo. Given the pace at which the industrial production of CNTs/CNFs is increasing, it is becoming of utmost importance to acquire comprehensive knowledge regarding their biological activity and their hazardous effects in humans. Animal studies carried out by inhalation showed that some CNTs/CNFs species can cause deleterious effects such as inflammation and lung tissue remodeling. Their physico-chemical properties, biological behavior and biopersistence make them similar to asbestos fibers. Human studies suggest some mild effects in workers handling CNT/CNF. However, owing to their cross-sectional design, researchers have been as yet unable to firmly demonstrate a causal relationship between such an exposure and the observed effects. Estimation of acceptable exposure levels should warrant a proper risk management. The aim of this review is to challenge the conception of CNTs/CNFs as a single, unified material entity and prompt the establishment of standardized hazard and exposure assessment methodologies able to properly feeding risk assessment and management frameworks.
... The 2011 IARC evaluation on carcinogenesis [62,63] has been downplayed and detracted by industry and captured agencies from the very beginning in spite of increasing evidence on harmful effects. However, IARC has decided that a new evaluation of cancer risks is top priority within a few years [100]. In this article we give some further data on the RF carcinogenesis. ...
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Some historical aspects on late lessons from early warnings on cancer risks with lost time for prevention are discussed. One current example is the cancer-causing effect from radiofrequency (RF) radiation. Studies since decades have shown increased human cancer risk. The fifth generation, 5G, for wireless communication is about to be implemented world-wide despite no comprehensive investigations of potential risks to human health and the environment. This has created debate on this technology among concerned people in many countries. In an appeal to EU in September 2017, currently endorsed by more than 400 scientists and medical doctors, a moratorium on the 5G deployment was required until proper scientific evaluation of negative consequences has been made (www.5Gappeal.eu). That request has not been taken seriously by EU. Lack of proper unbiased risk evaluation of the 5G technology makes adverse effects impossible to be foreseen. This disregard is exemplified by the recent report from the International Commission on non-ionizing radiation protection (ICNIRP) whereby only thermal (heating) effects from RF radiation are acknowledged despite a large number of reported non-thermal effects. Thus, no health effects are acknowledged by ICNIRP for non-thermal RF electromagnetic fields in the range of 100 kHz-300 GHz. Based on results in three case-control studies on use of wireless phones we present preventable fraction for brain tumors. Numbers of brain tumors of not defined type were found to increase in Sweden, especially in the age group 20-39 years in both genders, based on the Swedish Inpatient Register. This may be caused by the high prevalence of wireless phone use among children and in adolescence taking a reasonable latency period and the higher vulnerability to RF radiation among young persons.
... fumonisin B 1 (FB 1 ), FB 2 and FB 3 ), resulting in low yield and grain quality as a consequence of the FER disease [6]. From a toxicological standpoint, FB 1 is classified into group 2B as being possibly carcinogenic to humans [7]. The chemical structure of FB 1 is similar to sphingoid bases such as sphinganine and sphingosine. ...
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Fusarium ear rot (FER) caused by Fusarium verticillioides is one of the main fungal diseases in maize worldwide. To develop a pathogen-tailored FER resistant maize line for local implementation, insights into the virulence variability of a residing F. verticillioides population are crucial for developing customized maize varieties, but remain unexplored. Moreover, little information is currently available on the involvement of the archetypal defense pathways in the F. verticillioides–maize interaction using local isolates and germplasm, respectively. Therefore, this study aims to fill these knowledge gaps. We used a collection of 12 F. verticillioides isolates randomly gathered from diseased maize fields in the Vietnamese central highlands. To assess the plant’s defense responses against the pathogens, two of the most important maize hybrid genotypes grown in this agro-ecological zone, lines CP888 and Bt/GT NK7328, were used. Based on two assays, a germination and an in-planta assay, we found that line CP888 was more susceptible to the F. verticillioides isolates when compared to line Bt/GT NK7328. Using the most aggressive isolate, we monitored disease severity and gene expression profiles related to biosynthesis pathways of salicylic acid (SA), jasmonic acid (JA), abscisic acid (ABA), benzoxazinoids (BXs), and pathogenesis-related proteins (PRs). As a result, a stronger induction of SA, JA, ABA, BXs, and PRs synthesizing genes might be linked to the higher resistance of line Bt/GT NK7328 compared to the susceptible line CP888. All these findings could supply valuable knowledge in the selection of suitable FER resistant lines against the local F. verticllioides population and in the development of new FER resistant germplasms.
... In 2012, AFB 1 was classified as the Group 1 carcinogen (carcinogenic to humans) by the International Agency for Research on Cancer (IARC) (Haque et al., 2020). Further studies and conclusions by IARC and World Cancer Research Fund (WCRF) strongly supported the linkage of AFB 1 to liver cancer and other types of cancer risks (Marques et al., 2019;Claeys et al., 2020). In China, the risks of exposure to aflatoxin B 1 in foodstuffs or feeds still needed long-term supervision and control . ...
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Aflatoxins are naturally occurring high-toxic secondary metabolites, which cause worldwide environmental contaminations and wastes of food and feed resources and severely threaten human health. Thus, the highly efficient methods and technologies for detoxification of aflatoxins are urgently needed in a long term. In this work, we report the construction of recombinant Kluyveromyces lactis strains GG799(pKLAC1-Phs mnp ), GG799(pKLAC1-Plo mnp ), GG799(pKLAC1-Phc mnp ), and then the food-grade expression of the three manganese peroxidases in these strains, followed by the degradation of aflatoxin B 1 (AFB 1 ) using the fermentation supernatants. The expression of the manganese peroxidases was achieved in a food-grade manner since Kluyveromyces lactis is food-safe and suitable for application in food or feed industries. The inducible expression process of the optimal recombinant strain GG799(pKLAC1-Phc mnp ) and the aflatoxin B 1 degradation process were both optimized in detail. After optimization, the degradation ratio reached 75.71%, which was an increase of 49.86% compared to the unoptimized results. The degradation product was analyzed and determined to be AFB 1 -8,9-dihydrodiol. The recombinant strain GG799(pKLAC1-Phc mnp ) supernatants degraded more than 90% of AFB 1 in the peanut samples after twice treatments. The structural computational analysis for further mutagenesis of the enzyme PhcMnp was also conducted in this work. The food-grade recombinant yeast strain and the enzyme PhcMnp have potential to be applied in food or feed industries.
... Poor oral health, indicated by periodontal disease and tooth loss/decay, is a potentially important and preventable risk factor that involves shifts in the oral microbiome that may contribute to carcinogenesis in the esophagus. In fact, poor oral hygiene has been identified as one of the agents recommended for evaluation, with high priority for an upcoming IARC Monographs on the identification of carcinogenic hazards to humans [67]. Oral health-assessed by tooth loss; the sum of decayed, missing, or filled teeth (DMFT score); periodontal health; and oral hygiene practices (e.g., tooth brushing)-has been examined as a risk factor for ESCC in numerous epidemiologic studies [68][69][70][71][72][73][74][75][76][77][78]. ...
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Esophageal cancer (EC) is an aggressive malignant disease ranking amongst the leading causes of cancer deaths in the world. The two main histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have distinct geographic and temporal patterns and risk factor profiles. Despite decades of research, the factors underlying these geo-temporal patterns are still not fully understood. The human microbiome has recently been implicated in various health conditions and disease, and it is possible that the microbiome may play an important role in the etiology of EC. Although studies of the microbiome and EC are still in their early stages, we review our current understanding of the potential links between ESCC, EAC, and bacterial communities in the oral cavity and esophagus. We also provide a summary of the epidemiology of EC and highlight some key challenges and future directions.
... The need for a structured updated appraisal of this body of evidence is widely recognised. Non-ionising radiation (radiofrequency) is among the agents recommended with high priority for re-evaluation by the Advisory Group for the IARC Monographs during 2020-2024 (Marques et al. 2019). Two registered systematic reviews of epidemiological studies on RF-EMF and cancer are underway, focusing on exposures experienced by the general population (Farhat et al. 2020) and workers (Modenese et al. 2020). ...
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Background The World Health Organization (WHO) has an ongoing project to assess potential health effects of exposure to radiofrequency electromagnetic fields (RF-EMF) in the general and working population. Here we present the protocol for a systematic review of the scientific literature on cancer hazards from exposure to RF-EMF in humans, commissioned by the WHO as part of that project. Objective To assess the quality and strength of the evidence provided by human observational studies for a causal association between exposure to RF-EMF and risk of neoplastic diseases. Eligibility criteria We will include cohort and case-control studies investigating neoplasia risks in relation to three types of exposure to RF-EMF: near-field, head-localized, exposure from wireless phone use (SR-A); far-field, whole body, environmental exposure from fixed-site transmitters (SR-B); near/far-field occupational exposures from use of handheld transceivers or RF-emitting equipment in the workplace (SR-C). While no restriction on tumour type will be applied, we will focus on selected neoplasms of the central nervous system (brain, meninges, pituitary gland, acoustic nerve) and salivary gland tumours (SR-A); brain tumours and leukaemias (SR-B, SR-C). Information sources Eligible studies will be identified through Medline, Embase, and EMF-Portal. Risk-of-bias assessment We will use a tailored version of the OHAT's tool to evaluate the study's internal validity. Data synthesis We will consider separately studies on different tumours, neoplasm-specific risks from different exposure sources, and a given exposure-outcome pair in adults and children. When a quantitative synthesis of findings can be envisaged, the main aims of the meta-analysis will be to assess the strength of association and the shape of the exposure–response relationship; to quantify the degree of heterogeneity across studies; and explore the sources of inconsistency (if any). When a meta-analysis is judged inappropriate, we will perform a narrative synthesis, complemented by a structured tabulation of results and appropriate visual displays. Evidence assessment Confidence in evidence will be assessed in line with the GRADE approach. Funding This project is supported by the World Health Organization. Co-financing was provided by the New Zealand Ministry of Health; the Istituto Superiore di Sanità in its capacity as a WHO Collaborating Centre for Radiation and Health; ARPANSA as a WHO Collaborating Centre for Radiation Protection. Registration PROSPERO CRD42021236798.
... 22,23 Uranium at elevated concentrations in groundwater is a concern for its potential chemical toxicity, rather than its radiotoxicity. Although uranium has not yet been proven to be carcinogenic, 24 it is known to accumulate in and cause toxicity to kidneys, liver, and bones. 25 The World Health Organization prescribes drinking water limit of uranium as 30 μg L −1 . ...
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Firefighters may encounter items containing flame retardants (FRs), including organophosphate flame retardants (OPFRs) and polybrominated diphenyl ethers (PBDEs), during structure fires. This study utilized biological monitoring to characterize FR exposures in 36 firefighters assigned to interior, exterior, and overhaul job assignments, before and after responding to controlled residential fire scenarios. Firefighters provided four urine samples (pre-fire and 3-h, 6-h, and 12-h post-fire) and two serum samples (pre-fire and approximately 23-h post-fire). Urine samples were analyzed for OPFR metabolites, while serum samples were analyzed for PBDEs, brominated and chlorinated furans, and chlorinated dioxins. Urinary concentrations of diphenyl phosphate (DPhP), a metabolite of triphenyl phosphate (TPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), a metabolite of tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and bis(2-chloroethyl) phosphate (BCEtP), a metabolite of tris(2-chloroethyl) phosphate (TCEP), increased from pre-fire to 3-hr and 6-hr post-fire collection, but only the DPhP increase was statistically significant at a 0.05 level. The 3-hr and 6-hr post-fire concentrations of DPhP and BDCPP, as well as the pre-fire concentration of BDCPP, were statistically significantly higher than general population levels. BDCPP pre-fire concentrations were statistically significantly higher in firefighters who previously participated in a scenario (within the past 12 days) than those who were responding to their first scenario as part of the study. Similarly, firefighters previously assigned to interior job assignments had higher pre-fire concentrations of BDCPP than those previously assigned to exterior job assignments. Pre-fire serum concentrations of 2,3,4,7,8-pentachlorodibenzofuran (23478-PeCDF), a known human carcinogen, were also statistically significantly above the general population levels. Of the PBDEs quantified, only decabromodiphenyl ether (BDE-209) pre- and post-fire serum concentrations were statistically significantly higher than the general population. These results suggest firefighters absorbed certain FRs while responding to fire scenarios.
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Emerging studies have provided evidence on the carcinogenicity of radiofrequency radiation (RFR) from cell phones. This study aims to test the genetic susceptibility on the association between cell phone use and thyroid cancer. Population-based case-control study was conducted in Connecticut between 2010 and 2011 including 440 thyroid cancer cases and 465 population-based controls with genotyping information for 823 single nucleotide polymorphisms (SNPs) in 176 DNA genes. We used multivariate unconditional logistic regression models to estimate the genotype-environment interaction between each SNP and cell phone use and to estimate the association with cell phone use in populations according to SNP variants. Ten SNPs had P < 0.01 for interaction in all thyroid cancers. In the common homozygote groups, no association with cell phone use was observed. In the variant group (heterozygotes and rare homozygotes), cell phone use was associated with an increased risk for rs11070256 (odds ratio (OR): 2.36, 95% confidence interval (CI): 1.30-4.30), rs1695147 (OR: 2.52, 95% CI: 1.30-4.90), rs6732673 (OR: 1.59, 95% CI: 1.01-2.49), rs396746 (OR: 2.53, 95% CI: 1.13-5.65), rs12204529 (OR: 2.62, 95% CI: 1.33-5.17), and rs3800537 (OR: 2.64, 95% CI: 1.30-5.36) with thyroid cancers. In small tumors, increased risk was observed for 5 SNPs (rs1063639, rs1695147, rs11070256, rs12204529 and rs3800537), In large tumors, increased risk was observed for 3 SNPs (rs11070256, rs1695147, and rs396746). Our result suggests that genetic susceptibilities modify the associations between cell phone use and risk of thyroid cancer. The findings provide more evidence for RFR carcinogenic group classification.
Thesis
Smallholder farmers are a high-risk group for mycotoxin exposure since they often consume home-grown crops without any quality and safety control. These smallholder farms are often characterized by very typical growing-, harvest- and storage- practices. Moreover, these practices are inherent to their ethnicity. To our knowledge, no prior longitudinal comparative studies have addressed the relationship between traditional pre-, harvest, and post-harvest practices of different smallholder ethnic farmers and the contamination of maize by Fusarium verticillioides and its mycotoxins - fumonisins in different ethnic communities. Therefore, this doctoral dissertation aims to (1) uncover differences in traditional pre-, harvest, and post-harvest maize practices between two ethnic communities Ede and Kinh from the central highlands of Vietnam; (2) analyse the correlation between these traditional practices and the occurrence of F. verticillioides, and fumonisins; (3) evaluate the susceptibility of maize cultivars planted by the ethnic smallholders to F. verticillioides and lastly, (4) seek a biological control strategy against F. verticillioides. This work is timely and important because it is one of the first studies investigating the impact of ethnic customs on mycotoxin presence in the second most important staple food maize after rice in these subsistence farms. The outputs of this doctoral dissertation are a part of the blueprint towards good smallholder maize farms with high productivity, less mycotoxin contamination, and less grain loss. Optimistically, these mycotoxin mitigation strategies could be compatible with maize smallholders from other low and middle-income countries, especially Sub-Saharan Africa.
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Fumonisins are one of the most important mycotoxin classes due to their widespread occurrence and potential health threat to humans and animals. Currently, most of the research focuses on the control of fumonisin contamination in the food supply chain. In recent years, significant progress in biochemistry, enzymology, and genetic regulation of fumonisin biosynthesis has been achieved using molecular technology. Furthermore, new insights into the roles of fumonisins in the interaction between fungi and plant hosts have been reported. This review provides an overview of the current understanding of the biosynthesis and regulation of fumonisins. The ecological significance of fumonisins to Fusarium species that produce the toxins is discussed, and the complex regulatory networks of fumonisin synthesis is proposed.
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Current limits for exposures to nonionizing electromagnetic fields (EMF) are set, based on relatively short‐term exposures. Long‐term exposures to weak EMF are not addressed in the current guidelines. Nevertheless, a large and growing amount of evidence indicates that long‐term exposure to weak fields can affect biological systems and might have effects on human health. If they do, the public health issues could be important because of the very large fraction of the population worldwide that is exposed. We also discuss research that needs to be done to clarify questions about the effects of weak fields. In addition to the current short‐term exposure guidelines, we propose an approach to how weak field exposure guidelines for long‐term exposures might be set, in which the responsibility for limiting exposure is divided between the manufacturer, system operator, and individual being exposed. Bioelectromagnetics. © 2020 Bioelectromagnetics Society
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Background: There remains controversy as to whether cell phones cause cancer. We evaluated whether temporal changes in cell phone use and the incidence of glioma in Canada were consistent with the hypothesis of an increased risk. Design: We used data from the Canadian Cancer Registry to calculate annual incidence rates for glioma between 1992 and 2015. The annual number of new cell phone subscribers was determined using national industry statistics. The number of newly diagnosed gliomas was compared to the predicted number by applying risks from epidemiological studies to age-specific population estimates. Specifically, we calculated the "predicted" number of incident gliomas by determining the annual prevalence of cell phone users and years of use. These estimates were multiplied by the corresponding risk estimates to determine the predicted number of gliomas. Results: The number of cellular subscriptions in Canada increased from nil in the early-1980s to approximately 29.5 million in 2015. In contrast, age-standardized glioma incidence rates remained stable between 1992 and 2015. The application of risk estimates from i) a recent pooled analyses of Swedish case-control studies, ii) the 13 country INTERPHONE study, and iii) the Canadian data from INTERPHONE overestimated the observed number of glioma cases diagnosed in Canada in 2015 by 49%, 85%, and 63%, respectively. Interpretation: Predictions of glioma incidence counts using estimates of the relative risk of glioma due to cell phone use from case-control studies over-estimated the incidence rates of glioma in Canada. The absence of an elevation in incidence rates of glioma in conjunction with marked increases in cell phone use suggests that there may not be a causal link between cellphones and glioma.
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Recent years have witnessed an expansion of mutagenesis research focusing on experimentally modeled genome-scale mutational signatures of carcinogens and endogenous processes. Experimental mutational signatures can explain etiologic links to patterns found in human tumours that may be linked to same exposures, and can serve as biomarkers of exposure history and may even provide insights on causality. A number of innovative exposure models have been employed and reported, based on cells cultured in monolayers or in 3-D, on organoids, induced pluripotent stem cells, non-mammalian organisms, microorganisms and rodent bioassays. Here we discuss some of the latest developments and pros and cons of these experimental systems used in mutational signature analysis. Integrative designs that bring together multiple exposure systems (in vitro, in vivo and in silico pan-cancer data mining) started emerging as powerful tools to identify robust mutational signatures of the tested cancer risk agents. We further propose that devising a new generation of cell-based models is warranted to streamline systematic testing of carcinogen effects on the cell genomes, while seeking to increasingly supplant animal with non-animal systems to address relevant ethical issues and accentuate the 3R principles. We conclude that the knowledge accumulating from the growing body of signature modelling investigations has considerable power to advance cancer etiology studies and to support cancer prevention efforts through streamlined characterization of cancer-causing agents and the recognition of their specific effects.
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In recent years, there has been an increasing interest in investigating the carcinogenicity of mycotoxins in humans. This systematic review aims to provide an overview of data linking exposure to different mycotoxins with human cancer risk. Publications (2019 and earlier) of case–control or longitudinal cohort studies were identified in PubMed and EMBASE. These articles were then screened by independent reviewers and their quality was assessed according to the Newcastle–Ottawa scale. Animal, cross‐sectional, and molecular studies satisfied criteria for exclusion. In total, 14 articles were included: 13 case–control studies and 1 longitudinal cohort study. Included articles focused on associations of mycotoxin exposure with primary liver, breast, and cervical cancer. Overall, a positive association between the consumption of aflatoxin‐contaminated foods and primary liver cancer risk was verified. Two case–control studies in Africa investigated the relationship between zearalenone and its metabolites and breast cancer risk, though conflicting results were reported. Two case–control studies investigated the association between hepatocellular carcinoma and fumonisin B1 exposure, but no significant associations were observed. This systematic review incorporates several clear observations of dose‐dependent associations between aflatoxins and liver cancer risk, in keeping with IARC Monograph conclusions. Only few human epidemiological studies investigated the associations between mycotoxin exposures and cancer risk. To close this gap, more in‐depth research is needed to unravel evidence for other common mycotoxins, such as deoxynivalenol and ochratoxin A. The link between mycotoxin exposures and cancer risk has mainly been established in experimental studies, and needs to be confirmed in human epidemiological studies to support the evidence‐based public health strategies.
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Acrylamide is a suspected human carcinogen formed during high-temperature cooking of starch-rich foods. It is metabolised by cytochrome P450 2E1 to its reactive metabolite glycidamide, which forms pre-mutagenic DNA adducts. Using the human TP53 knock-in (Hupki) mouse embryo fibroblasts (HUFs) immortalisation assay (HIMA), acrylamide- and glycidamide-induced mutagenesis was studied in the tumour suppressor gene TP53. Selected immortalised HUF clones were also subjected to next-generation sequencing to determine mutations across the whole genome. The TP53-mutant frequency after glycidamide exposure (1.1 mM for 24 h, n = 198) was 9% compared with 0% in cultures treated with acrylamide [1.5 (n = 24) or 3 mM (n = 6) for 48 h] and untreated vehicle (water) controls (n = 36). Most glycidamide-induced mutations occurred at adenines with A > T/T > A and A > G/T > C mutations being the most common types. Mutations induced by glycidamide occurred at specific TP53 codons that have also been found to be mutated in human tumours (i.e., breast, ovary, colorectal, and lung) previously associated with acrylamide exposure. The spectrum of TP53 mutations was further reflected by the mutations detected by whole-genome sequencing (WGS) and a distinct WGS mutational signature was found in HUF clones treated with glycidamide that was again characterised by A > G/T > C and A > T/T > A mutations. The WGS mutational signature showed similarities with COSMIC mutational signatures SBS3 and 25 previously found in human tumours (e.g., breast and ovary), while the adenine component was similar to COSMIC SBS4 found mostly in smokers' lung cancer. In contrast, in acrylamide-treated HUF clones, only culture-related background WGS mutational signatures were observed. In summary, the results of the present study suggest that glycidamide may be involved in the development of breast, ovarian, and lung cancer.
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IARC Monographs are globally-recognized assessments of carcinogenicity published by International Agency for Research on Cancer and directed to national authorities as a contribution to public health. Currently, though not constraining the scope of studies examined, Monographs are declared to involve only hazard identification: a scenario which then dictates that overall evaluations involve a single sentence referencing only the likelihood of carcinogenicity. Consequently, for notable evaluations, commentators explain what particular Monographs encompass, sometimes indicating which national authority might act. However, upon examination, IARC Monographs cannot be recognized as only hazard identification because they include assessment of specified circumstances of exposure, document levels of exposure to particular agents and identify organ site(s) for tumours. Comparisons with assessments of carcinogenicity made by US National Toxicology Program and by World Cancer Research Fund indicate that Monographs represent a singular methodology, not precisely aligned with hazard identification or risk assessment. Hence, all key findings relevant to public health in particular Monographs may be prominently and accessibly communicated. Where currently documented, these findings specifically include situation(s) resulting in highest exposure and known or likely tumour site(s). Correspondingly-less reliance on commentators, and greater insight by the wider community, may be further achieved by WHO, in consultation with IARC, describing the type of national authority relevant to particular evaluations, this information being complementary to relevant Monographs. No changes in the scope, structure or content of Monographs are necessitated by such proposals. Examples of key findings, and the relevant national authority, are provided in respect of several notable Monographs.
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Objectives: Pyrethroid insecticides have been linked with multiple health outcomes. One study reported an association with increased all-cause and cardiovascular mortality. Given the widespread use of pyrethroids, these findings warrant confirmation. We explored associations of permethrin/pyrethroid use with overall and cause-specific mortality among 50 665 licensed pesticide applicators in the Agricultural Health Study. Methods: At enrolment (1993-1997), participants self-reported information on permethrin/pyrethroid use. Information on causes of death came from linkage with death registries through 2016. We used Cox proportional hazards models to estimate HRs and 95% CIs with adjustment for potential confounders. Results: Over an average 21 years of follow-up, 19.6% (9,955) of the cohort died. We found no clear evidence that ever-use of permethrin/pyrethroid was associated with elevated overall mortality or with mortality from most causes examined. There was suggestive evidence, based on a small number of deaths among those exposed, for elevated pyrethroid-associated mortality from some neurological, respiratory and genitourinary diseases in the overall sample and from lung cancer among never-smokers. Conclusion: Although based on mortality, which is also affected by survival, rather than incidence, these findings are biologically plausible, and future investigations in other populations may be warranted.
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Mycotoxins are increasingly considered as micropollutants in the environment. Fumonisins, as one of the most important mycotoxins, cause potential health threats to humans and animals due to their ubiquitous contamination on cereals, fruit, vegetables and other environmental samples around the world. However, the contribution of fumonisins to the interaction of fungi with plant hosts is not still fully understood. Here, we investigated the effect of fumonisin B1 (FB1) on the infection of Fusarium proliferatum on banana fruit and the underlying mechanisms from the host perspective. Our results found that FB1 treatment increased the aggressiveness of F. proliferatum on banana fruit and inhibited the defense ability of banana fruit via decreasing phenylalanine ammonia lyase (PAL), β-1,3-glucanase (GLU) and chitinase (CHI) activities. Meanwhile, FB1 accelerated cell death, indicated by higher relative conductivity, MDA content and higher transcripts of cell death-related genes. FB1 treatment resulted in higher hydrogen peroxide (H2O2) content possibly due to MaRBOHs induction. These consequences accelerated the ROS-dependent cell death, which subsequently result in reduction of disease resistance of banana fruit. Additionally, energy metabolism and MaDORN1s-mediated eATP signaling might involve in FB1-meidiated suppression of banana defense responses. Collectively, results of the current study indicated that FB1 contamination triggered the cell death of banana peel, subsequently instigating the invasion and growth of F. proliferatum on banana fruit. In summary, for the first time, we demonstrated a previously unidentified role of fumonisins as a potential virulence factor of F. proliferatum in modulating fruit defense response, which provides new insight on the biological roles of fumonisins.
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Background Aspartame is one of the world’s most widely used artificial sweeteners and is an ingredient in more than 5000 food products globally. A particularly important use is in low-calorie beverages consumed by children and pregnant women. The Ramazzini Institute (RI) reported in 2006 and 2007 that aspartame causes dose-related increases in malignant tumors in multiple organs in rats and mice. Increased cancer risk was seen even at low exposure levels approaching the Acceptable Daily Intake (ADI). Prenatal exposures caused increased malignancies in rodent offspring at lower doses than in adults. These findings generated intense controversy focused on the accuracy of RI’s diagnoses of hematopoietic and lymphoid tissue tumors (HLTs). Critics made the claim that pulmonary lesions observed in aspartame-exposed animals were inflammatory lesions caused by Mycoplasma infection rather than malignant neoplasms. Methods To address this question, RI subjected all HLTs from aspartame-exposed animals to immunohistochemical analysis using a battery of markers and to morphological reassessment using the most recent Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria. Findings This immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in 92.3% of cases. Six lesions originally diagnosed as lymphoma (8% of all HLTs) were reclassified: 3 to lymphoid hyperplasia, and 3 to chronic inflammation with fibrosis. There was no evidence of Mycoplasma infection. Interpretation These new findings confirm that aspartame is a chemical carcinogen in rodents. They confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies. These findings are of great importance for public health. In light of them, we encourage all national and international public health agencies to urgently reexamine their assessments of aspartame’s health risks - especially the risks of prenatal and early postnatal exposures. We call upon food agencies to reassess Acceptable Daily Intake (ADI) levels for aspartame. We note that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame’s carcinogenicity to humans.
Article
Background Systematic evaluation of literature data on the cancer hazards of human exposures is an essential process underlying cancer prevention strategies. The scope and volume of evidence for suspected carcinogens can range from very few to thousands of publications, requiring a complex, systematically planned, and critical procedure to nominate, prioritize and evaluate carcinogenic agents. To aid in this process, database fusion, cheminformatics and text mining techniques can be combined into an integrated approach to inform agent prioritization, selection, and grouping. Results We have applied these techniques to agents recommended for the IARC Monographs evaluations during 2020–2024. An integration of PubMed filters to cover cancer epidemiology, key characteristics of carcinogens, chemical lists from 34 databases relevant for cancer research, chemical structure grouping and a literature data-based clustering was applied in an innovative approach to 119 agents recommended by an advisory group for future IARC Monographs evaluations. The approach also facilitated a rational grouping of these agents and aids in understanding the volume and complexity of relevant information, as well as important gaps in coverage of the available studies on cancer etiology and carcinogenesis. Conclusion A new data-science approach has been applied to diverse agents recommended for cancer hazard assessments, and its applications for the IARC Monographs are demonstrated. The prioritization approach has been made available at www.cancer.idsl.me site for ranking cancer agents.
Article
Exposure to endocrine-disrupting chemicals, like Polybrominated diphenyl ethers (PBDEs), is suspected of playing a role in the occurrence of breast cancer. Moreover, there is growing evidence that food chemical contaminants, especially lipophilic ones such as PBDEs, could interact with different components of the diet. The objective of the present study was to assess the association between dietary intake of PBDEs and breast cancer risk in the French E3N cohort study, and to investigate the potential modification of this association by vegetable oil consumption. The study included 67 879 women. Intakes of eight PBDEs were estimated using food consumption data from a validated semi-quantitative food frequency questionnaire, and food contamination levels measured by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES). Cox proportional hazards models were used to estimate Hazard Ratios (HR) and 95% Confidence Intervals (CI) for the association between total PBDEs dietary intake and breast cancer risk. Interaction measures for vegetable oil consumption were estimated on both additive and multiplicative scales. The women were followed for a maximum of 21.4 years, and 5 686 developed an incident breast cancer. A positive linear trend was highlighted between dietary intake of PBDEs in quintile groups and breast cancer risk, borderline with statistical significance (p-trend=0.06, HRQ5vsQ1 and 95%CI: 1.09 [0.99;1.20]). Interaction measures for vegetable oil consumption were significant in both additive and multiplicative scales. Higher effect sizes of the association were highlighted in high consumers of vegetable oil, i.e. ≥4.6 g/day (HRQ5vsQ1 and 95%CI: 1.23 [1.08; 1.40]), and almost no effect were found in low consumers (HRQ5vsQ1 and 95%CI: 0.97 [0.86; 1.10]). Highlighting such interactions between nutrients and chemicals is crucial to develop efficient dietary recommendations to limit the negative health effects associated with exposure to food chemical contaminants.
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Background: Identifying cancer hazards is the first step towards cancer prevention. The IARC Monographs Programme, which has evaluated nearly 1000 agents for carcinogenic potential since 1971, typically selects agents for hazard identification on the basis of public nominations, expert advice, published data on carcinogenicity, and public health importance. Objectives: Here we present a novel and complementary strategy for identifying agents for hazard evaluation using chemoinformatics, database integration and automated text mining. Discussion: To inform selection among a broad range of pesticides nominated for evaluation, we identified and screened nearly 6000 relevant chemical structures, thereafter systematically compiled information on 980 pesticides, creating chemical similarity network maps that allowed cluster visualization by chemical similarity, pesticide class, and publicly available information concerning cancer epidemiology, cancer bioassays, and carcinogenic mechanisms. For the IARC Monograph meetings that took place in March and June 2015, this approach supported high priority evaluation of glyphosate, malathion, parathion, tetrachlorvinphos, diazinon, DDT, lindane, and 2,4-D. Conclusions: This systematic approach, accounting for chemical similarity and overlaying multiple data sources, can be used by risk assessors as well as researchers to systematize, inform and increase efficiency in selecting and prioritizing agents for hazard identification, risk assessment, regulation or further investigation. This approach could be extended to an array of outcomes and agents, including occupational carcinogens, drugs, and foods.
International Agency for Research on Cancer
International Agency for Research on Cancer. Preamble to the IARC Monographs. 2019. https://monographs.iarc.fr/wp-content/ uploads/2019/01/Preamble-2019.pdf (accessed April 16, 2019).
Sixtieth Session of the IARC Governing Council
International Agency for Research on Cancer. Sixtieth Session of the IARC Governing Council, GC/60/13. 2018. http://governance.iarc.fr/GC/ GC60/En/Docs/GC60_13_CoordinationWHO. pdf (accessed April 12, 2019).