1. IntroductionThe correlation between exposure to chemical compounds and the onset of cancer pathologies has long been the subject of study in toxicology, epidemiology, and medicine. Various international organizations, including the International Agency for Research on Cancer (IARC) and the European Chemicals Agency (ECHA), classify and assess ch... (Read the full Tiiip)
1. IntroductionThe correlation between exposure to chemical compounds and the onset of cancer pathologies has long been the subject of study in toxicology, epidemiology, and medicine. Various internat ...
The correlation between exposure to chemical compounds and the onset of cancer pathologies has long been the subject of study in toxicology, epidemiology, and medicine. Various international organizations, including the International Agency for Research on Cancer (IARC) and the European Chemicals Agency (ECHA), classify and assess chemical compounds based on their hazards, including their potential carcinogenicity. The goal of this report is to provide an overview of some commonly used or industrially relevant chemical compounds and the possible cancer risks associated with them.
2. Carcinogen Classification
IARC classifies carcinogenic substances into distinct groups:
Group 1: Carcinogenic to humans (sufficient evidence).
Group 2A: Probably carcinogenic to humans (limited evidence in humans but sufficient evidence in animals).
Group 2B: Possibly carcinogenic to humans (limited evidence in humans and in animals).
Group 3: Not classifiable as to its carcinogenicity to humans.
Group 4: Probably not carcinogenic to humans (rare in this classification).
This classification is constantly updated based on new scientific findings.
3. Chemical Compounds of Industrial and/or Environmental Relevance
3.1. Benzene
Origin: Used as an industrial solvent, present in petroleum products, and formed by the incomplete combustion of organic material.
IARC Classification: Group 1 (carcinogenic to humans).
Main health effects: Chronic exposure to benzene is associated with the onset of leukemias (particularly acute myeloid leukemia), lymphomas, and other hematological disorders.
Mechanism of action: Reactive metabolites (e.g., benzene epoxide) can damage DNA and alter the production of hematopoietic cells.
3.2. Formaldehyde
Origin: Used in everyday products (resins, adhesives, plywood, cosmetics) and released during combustion processes.
IARC Classification: Group 1.
Main health effects: High-concentration exposure is associated with an increased risk of nasopharyngeal cancer and possible neoplasms of the upper respiratory tract.
Mechanism of action: It can form cross-links with proteins and nucleic acids, causing mutations and genetic instability.
3.3. Asbestos
Origin: A generic name for a group of natural fibrous minerals (chrysotile, crocidolite, amosite, etc.), historically used as thermal and acoustic insulation.
IARC Classification: Group 1.
Main health effects: Pleural and peritoneal mesothelioma, lung cancer, and other pulmonary diseases (asbestosis).
Mechanism of action: Asbestos fibers, once inhaled, can cause oxidative stress, chronic inflammation, and DNA damage in lung cells.
3.4. Polycyclic Aromatic Hydrocarbons (PAHs)
Origin: By-products of the incomplete combustion of organic materials (coal, oil, wood). Also present in cigarette smoke and in foods cooked at high temperatures.
IARC Classification: Some PAHs are classified in Group 1 (e.g., benzo[a]pyrene).
Main health effects: They can induce tumors in various organs (skin, lungs, gastrointestinal tract).
Mechanism of action: PAHs can be metabolized into reactive intermediates that form adducts with DNA, causing mutations during cell replication.
3.5. Vinyl Chloride
Origin: Mainly used in the production of PVC (polyvinyl chloride).
IARC Classification: Group 1.
Main health effects: Hepatic angiosarcoma (a rare liver cancer), with possible effects on other organs through prolonged exposure.
Mechanism of action: The reactive metabolite chloroethylene oxide can damage DNA in liver cells.
3.6. Nitroso Compounds (Nitrosamines)
Origin: Can form during certain food production processes, in tobacco smoke, and in specific industrial processes.
IARC Classification: Some nitrosamines (e.g., N-nitrosodimethylamine, NDMA) are classified as Group 2A or 2B, while some are in Group 1, depending on their chemical structure.
Main health effects: Liver, gastric, and esophageal cancers.
Mechanism of action: Highly reactive intermediate metabolites can interact with DNA, causing point mutations and multiple lesions.
3.7. Dioxins (e.g., TCDD)
Origin: By-products of industrial combustion processes and certain synthetic chemical processes.
IARC Classification: TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) is classified in Group 1.
Main health effects: Increased risk of tumors in various organs (liver, lymphatic system), as well as endocrine and immunological alterations.
Mechanism of action: Acts primarily through the AhR (Aryl hydrocarbon Receptor), modulating gene expression and potentially promoting abnormal cell proliferation.
4. General Mechanisms of Chemical Carcinogenesis
DNA Damage (Initiation): Many chemicals require metabolic activation to become electrophilic metabolites capable of binding to DNA (adduct formation). If these lesions are not repaired, they can result in cancer-causing mutations.
Promotion: Some substances, though not mutagenic per se, can promote the proliferation of already-mutated cells, favoring clonal expansion.
Progression: Further mutations and genetic instability lead to the formation of malignant cells, capable of invading tissues and metastasizing.
This multistep process (initiation, promotion, and progression) is known as “multistage carcinogenesis.” Individual susceptibility, genetic predisposition, dose, and duration of exposure play a critical role in the onset of oncological disease.
5. Factors Influencing Risk
Dose and duration of exposure: Higher contaminant concentrations and prolonged exposure increase the risk of developing cancer.
Route of exposure: Inhalation, ingestion, or dermal contact can differently affect the absorption and toxicokinetics of a substance.
Environmental conditions: The use of personal protective equipment (PPE), proper workplace ventilation, and effective chemical waste disposal systems are essential to reduce risk.
Individual factors: Genetic susceptibility, lifestyle habits (smoking, diet, alcohol), and pre-existing health conditions.
6. Conclusions
Assessing the carcinogenic risk associated with chemical compounds requires an interdisciplinary approach involving toxicology, epidemiology, molecular biology, and occupational medicine. Understanding the mechanisms of action, combined with cohort studies and experimental analyses, is essential to establish safe exposure limits and adopt appropriate preventive measures.
The compounds discussed in this report (benzene, formaldehyde, asbestos, PAHs, vinyl chloride, nitrosamines, dioxins) are only some of the most well-known examples, but many other substances are currently under evaluation. In the interest of public health, it is crucial that regulations (at both national and international levels) keep pace with the scientific evidence in order to minimize the risk of cancer associated with exposure to hazardous chemicals.
Endocrine disrupters
Synthetic chemicals that can reach and alter normal endocrine homeostasis act by reversibly modulating hormonal activity or causing damage. Since the endocrine system is by nature sensitive and dynamically modulated on a dose-response basis, it is important to focus on the quantity of substances that could cause damage to the system.
Endocrine disrupters(EDS) are defined by the World Health Organisation as ‘an endocrine disruptor is an exogenous substance or mixture that alters function(s) of the endocrine system and consequently causes adverse health effects in an intact organism, or its progeny, or (sub)populations’.
Among the most common endocrine disruptors, pesticides are the most widespread, and since 1939, the year DDT was discovered, the chemical industries have massively produced a myriad of substances to defend us from insects, rodents, fungi, weeds and pests (2).
In addition to their immediate and direct danger, pesticides can remain on the ground, exerting their action, for a long time, penetrate the soil polluting water, settle in vertebrates and invertebrates and, through the latter, trace their action back to predators.
Some endocrine disruptors can act on DNA, others can disrupt reproductive development, and others have a link to prostate cancer, but studies are sometimes conflicting because age, sex, duration of exposure and, as we said before, quantities play a role as co-factors.
Parabens are preservative chemical compounds that have been the subject of attention in the scientific literature as possible endocrine disruptors (particularly propylparaben and butylparaben), i.e. with the possibility of damaging the hormone-producing glands in our bodies, particularly in the breasts. The 2004 study by Darbre et al. showed that parabens remain in our bodies as intact esters (2). Following this study, some of the scientific literature in 2005 and 2006 cast doubt on Darbre's conclusions and claimed they were limited. However, both the US FDA and the European SCCP authorised in 2006 the use of a single paraben in cosmetic products at a concentration of 0.4% and the use of total parabens at a concentration of 0.8%. However, there is no shortage of studies that consider the restrictions unnecessary: M. G. Kirchhof et al. in 2013 found that parabens are among the safest and most well-tolerated preservatives and that current data do not support drastic regulations or personal exposure restrictions. In 2014 Darbre published an additional study showing how parabens can cause DNA damage, and in 2017 another study on the relationship between parabens, endocrine regulation of energy metabolism, and adipose tissue structure. (3).
The alternative is represented by natural products.
(1) Tabb MM, Blumberg B. New modes of action for endocrine-disrupting chemicals. Mol Endocrinol. 2006 Mar;20(3):475-82. doi: 10.1210/me.2004-0513.
Abstract. Endocrine-disrupting chemicals (EDC) are commonly considered to be compounds that mimic or block the transcriptional activation elicited by naturally circulating steroid hormones by binding to steroid hormone receptors. For example, the Food Quality Protection Act of 1996 defines EDC as those, that "may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen, or other such endocrine effect as the Administrator may designate." The definition of EDC was later expanded to include those that act on the estrogen, androgen, and thyroid hormone receptors. In this minireview, we discuss new avenues through which xenobiotic chemicals influence these and other hormone-dependent signaling pathways. EDC can increase or block the metabolism of naturally occurring steroid hormones and other xenobiotic chemicals by activating or antagonizing nuclear hormone receptors. EDC affect the transcriptional activity of nuclear receptors by modulating proteasome-mediated degradation of nuclear receptors and their coregulators. Xenobiotics and environmental contaminants can act as hormone sensitizers by inhibiting histone deacetylase activity and stimulating mitogen-activated protein kinase activity. Some endocrine disrupters can have genome-wide effects on DNA methylation status. Others can modulate lipid metabolism and adipogenesis, perhaps contributing to the current epidemic of obesity. Additional elucidation of these new modes of endocrine disruption will be key in understanding the nature of xenobiotic effects on the endocrine system.
(2) Andersen HR, Vinggaard AM, Rasmussen TH, Gjermandsen IM, Bonefeld-Jørgensen EC. Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro. Toxicol Appl Pharmacol. 2002 Feb 15;179(1):1-12. doi: 10.1006/taap.2001.9347.
Abstract. Twenty-four pesticides were tested for interactions with the estrogen receptor (ER) and the androgen receptor (AR) in transactivation assays. Estrogen-like effects on MCF-7 cell proliferation and effects on CYP19 aromatase activity in human placental microsomes were also investigated. Pesticides (endosulfan, methiocarb, methomyl, pirimicarb, propamocarb, deltamethrin, fenpropathrin, dimethoate, chlorpyriphos, dichlorvos, tolchlofos-methyl, vinclozolin, iprodion, fenarimol, prochloraz, fosetyl-aluminum, chlorothalonil, daminozid, paclobutrazol, chlormequat chlorid, and ethephon) were selected according to their frequent use in Danish greenhouses. In addition, the metabolite mercaptodimethur sulfoxide, the herbicide tribenuron-methyl, and the organochlorine dieldrin, were included. Several of the pesticides, dieldrin, endosulfan, methiocarb, and fenarimol, acted both as estrogen agonists and androgen antagonists. Prochloraz reacted as both an estrogen and an androgen antagonist. Furthermore, fenarimol and prochloraz were potent aromatase inhibitors while endosulfan was a weak inhibitor. Hence, these three pesticides possess at least three different ways to potentially disturb sex hormone actions. In addition, chlorpyrifos, deltamethrin, tolclofos-methyl, and tribenuron-methyl induced weak responses in one or both estrogenicity assays. Upon cotreatment with 17beta-estradiol, the response was potentiated by endosulfan in the proliferation assay and by pirimicarb, propamocarb, and daminozid in the ER transactivation assay. Vinclozolin reacted as a potent AR antagonist and dichlorvos as a very weak one. Methomyl, pirimicarb, propamocarb, and iprodion weakly stimulated aromatase activity. Although the potencies of the pesticides to react as hormone agonists or antagonists are low compared to the natural ligands, the integrated response in the organism might be amplified by the ability of the pesticides to act via several mechanism and the frequent simultaneous exposure to several pesticides.
Abstract. Purpose of review: The purpose of this review was to summarise current evidence that some environmental chemicals may be able to interfere in the endocrine regulation of energy metabolism and adipose tissue structure. Recent findings: Recent findings demonstrate that such endocrine-disrupting chemicals, termed "obesogens", can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and as ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing the retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer.
