The International Agency for Research on Cancer (IARC) has classified acrylonitrile as "carcinogenic to humans" and talc as "probably carcinogenic to humans" in a new evaluation.
These findings, published in The Lancet Oncology, will be included in Volume 136 of the IARC Monographs. The classifications were determined by a working group of 29 scientists from 13 countries who met at the IARC in Lyon, France.
Acrylonitrile Classification
Acrylonitrile, a high production–volume chemical used primarily in manufacturing, was classified as "carcinogenic to humans" (Group 1) based on sufficient evidence for cancer in humans, sufficient evidence for cancer in experimental animals, and strong mechanistic evidence in experimental systems.
The evaluation found sufficient evidence that acrylonitrile causes lung cancer in humans, and limited evidence of elevated risk for bladder cancer. A high-quality pooled cohort study of eight facilities showed a quantitative exposure-response association for lung cancer mortality, accounting for major confounding factors and healthy worker survivor bias. Other studies, including a large case-control study, also observed associations between acrylonitrile exposure and lung cancer.
In animal studies, acrylonitrile caused:
- Forestomach squamous cell carcinoma in male and female B6C3F1 mice (gavage administration)
- Brain astrocytoma and Zymbal gland carcinoma in male and female Sprague-Dawley (SD) rats (oral administration)
- Spinal cord astrocytoma, forestomach squamous cell carcinoma, and intestinal adenocarcinoma in male SD rats (oral administration)
- Mammary gland carcinoma in female SD rats (oral administration)
- Oligodendroglioma and Zymbal gland carcinoma in male offspring of SD rats (two-generation inhalation study)
- Oligodendroglioma, extrahepatic angiosarcoma, mammary gland adenocarcinoma, and lymphohaematopoietic tumors in female offspring of SD rats (two-generation inhalation study).
Mechanistic evidence showed that acrylonitrile:
- Binds to nucleic acids, hemoglobin, and multiple tissue proteins
- Is genotoxic, inducing genetic alterations in various experimental systems
- Induces oxidative stress
- Causes immortalization and cell transformation in vitro
- Alters cell proliferation, cell death, or nutrient supply.
Talc Classification
Talc, a high production–volume mineral used in various industries, was classified as "probably carcinogenic to humans" (Group 2A) based on limited evidence for cancer in humans, sufficient evidence for cancer in experimental animals, and strong mechanistic evidence in human primary cells and experimental systems.
The evaluation found limited evidence that talc causes ovarian cancer in humans. Recent studies, including pooled cohort and case-control studies, have reported more consistent positive associations for ever-use versus never-use of talc-based body powder, with evidence of an exposure-response relationship. However, potential bias from differential exposure misclassification and confounding by asbestos contamination could not be ruled out.
In animal studies, talc caused:
- Bronchioloalveolar carcinoma, bronchioloalveolar adenoma or carcinoma (combined), malignant pheochromocytoma, benign or malignant pheochromocytoma (combined), bilateral benign pheochromocytoma, and bilateral malignant pheochromocytoma of the adrenal medulla in female SD rats (inhalation exposure)
- Benign, malignant, or complex pheochromocytoma (combined) of the adrenal medulla in male SD rats (inhalation exposure).
Mechanistic evidence showed that talc:
- Induces chronic inflammation in various tissues following different routes and exposures
- Alters cell proliferation, cell death, or nutrient supply
- Promotes anchorage-independent growth in human primary and immortalized ovarian epithelial cells
- Induces secretion of factors that promote fibroblast proliferation in human primary mesothelial cells
- Causes hyperplasia in the respiratory system of rodents exposed chronically by inhalation or acutely by intratracheal administration.
These classifications supersede previous evaluations of talc and acrylonitrile. The IARC working group's assessments were based on a comprehensive review of available evidence, including epidemiological studies, animal experiments, and mechanistic data.
The findings underscore the importance of continued research and risk assessment for these widely used substances.
All authors declared no competing interests.