L'Association pour la santé environnementale du Québec / Environmental Health Association of Québec

Toxicology: it’s not just the dose that makes the poison


Toxicology began as the science of poisons. History shows that civilizations actually used their knowledge of poisons to murder and replace numerous kings and emperors. The concept of the use of chemical substances changed in the 15th century when Paracelsus, considered the father of modern toxicology, stated, “It’s the dose that makes the poison.” He understood that for every substance there is a dose which is harmful and a dose which is therapeutic or not harmful.i


This concept has been extremely important, because of the industrial revolution and especially in the last century. People are now exposed to many different chemicals. The average person is contaminated with up to 200 chemicals starting from conceptionii iii and so knowledge of the toxicological properties of these chemicals is extremely important in order to protect public health. Toxicology has evolved from the science of poisons to include the science of safety. However, despite efforts to consolidate the published toxicity data, there are thousands of environmental chemicals for which little to no data currently exist.iv v

More than one dose?

We now know that more than one dose makes the poison, that toxins can exert different effects with different doses. For example, there are chemicals, such as plasticizers, that can interfere with hormone actions at tiny doses, yet can exhibit different effects at higher doses. This is known as a nonmonotonic vii

Size makes the poison

Toxins come in all sizes, such as the particulate matter that dominates air pollution. The smaller the size of the particulates, the deeper they can penetrate the lungs, the easier they are absorbed, and the more likely they can enter organs and cells and exert their toxic effects. Size makes the poison.viii ix

Timing makes the poison

There are different windows of increased vulnerability to toxins during our lives. Timing makes the poison too. We are vulnerable in utero, and the potential damage depends on which organ is developing the most when the exposure occurs.x Children are also more vulnerable because their organs are still developing. Pregnant women are more at risk for specific conditions such as preeclampsia.xi And seniors are more at risk too. For example, there are worse survival rates after a stroke, depending on the levels of pollution where one lives.xii

Duration makes the poison

Duration of exposure also makes the poison. We are now seeing that exposures starting in utero and early childhood increase the likelihood that in later life we will develop chronic cardiovascular, respiratory and or immunological diseases, or some cancers.xiii

Real life complex mixtures make the poison

Toxicology studies chemical exposures in the laboratory to look for the toxic dose. Real life studies are done by epidemiologists, who look for patterns of change in the population associated with chronic exposures. In real life, exposures are multiple and simultaneous, yet constantly in flux. We know that living cells function through the interactions of different molecules. Systems biology studies these biological networks,xiv xv and systems toxicology studies the perturbations in these biological networks following exposure to chemical substances.xvi One thing we know from systems toxicology is that pollution exposures can stimulate and sensitize cell surface receptors that respond to a multitude of chemicals,xvii and that developing multiple chemical sensitivities is a risk from pollution exposures.xviii

Real life – our bodies and our surroundings are contaminated with synthetic chemicals. Remember that just because a chemical is used commercially does not mean that it has been adequately tested and is safe. The best advice is to adhere to the Precautionary Principalxix and try to reduce or eliminate exposures to pollutants whenever you can. One dose might not make a poison. But multiple, simultaneous doses for your whole life likely do.

i Grandjean P. Paracelsus Revisited: The Dose Concept in a Complex World. Basic Clin Pharmacol Toxicol. 2016 Aug;119(2):126-32.

ii Environmental Working Group. Body Burden: The Pollution in Newborns; July 2005 Accessed February 14, 2021.

iii Environmental Working Group. Pollution in Minority Newborns: BPA and Other Cord Blood Pollutants; November 2009. Accessed February 14, 2021.

iv Judson R. The toxicity data landscape for environmental chemicals. Environ Health Perspect. 2009 May; 117(5): 685–695

v Silins I. Combined toxic exposures and human health: biomarkers of exposure and effect. Int J Environ Res Public Health. 2011 Mar;8(3):629-47.

vi EPA. Environmental Protection Agency. “Review of the Environmental Protection Agency’s State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors” at [Internet]. Accessed Feb 14, 2021. Available from:

vii Xu Z, Liu J, Wu X, Huang B, Pan X. Nonmonotonic responses to low doses of xenoestrogens: A review. Environ Res. 2017 May;155:199-207. doi: 10.1016/j.envres.2017.02.018. Epub 2017 Mar 10. PMID: 28231547.

viii Gillespie P, Tajuba J, Lippmann M, Chen L-C, Veronesi B. Particulate Matter Neurotoxicity in Culture is Size-Dependent. Neurotoxicology. 2013 May;36:112–7.

ix Win-Shwe T-T, Fujimaki H. Nanoparticles and neurotoxicity. Int J Mol Sci. 2011;12(9):6267–80.

x Cooper K. Early exposures to hazardous chemicals/pollution and associations with chronic disease: a scoping review. Report from the Canadian Environmental Law Association, the Ontario College of Family Physicians and the Environmental Health Institute of Canada; 2011. Accessed February 14, 2021.

xi Mendola P. Air pollution exposure and preeclampsia among US women with and without asthma. Environ Res. 2016 Apr 14;148:248-255.

xii Maheswaran R. Impact of outdoor air pollution on survival after stroke. Stroke. 2010;41:869–877.

xiii Cooper K. Early exposures to hazardous chemicals/pollution and associations with chronic disease: a scoping review. Report from the Canadian Environmental Law Association, the Ontario College of Family Physicians and the Environmental Health Institute of Canada; 2011. Accessed February 14, 2021.

xiv Kitano H. Systems biology: a brief overview. Science. 2002;295:1662–1664

xv Ma’ayan A. Complex systems biology. J R Soc Interface. 2017 Sep;14(134):20170391.

xvi Sturla SJ, Boobis AR, FitzGerald RE, Hoeng J, Kavlock RJ, Schirmer K, Whelan M, Wilks MF, Peitsch MC. Systems toxicology: from basic research to risk assessment. Chem Res Toxicol. 2014 Mar 17;27(3):314-29.

xvii Talavera K, Startek JB, Alvarez-Collazo J, Boonen B, Alpizar YA, Sanchez A, et al. Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease. Physiol Rev. 2020 Apr 1;100(2):725–803.

xviii Molot, J., 2013. 12,000 Canaries Can’t Be Wrong. Establishing the New Era of Environmental Medicine. EnviroHealth Publications, Canada.

xix Ashford NA. Implementing the Precautionary Principle: incorporating science, technology, fairness, and accountability in environmental, health, and safety decisions. Int J Occup Med Environ Health. 2004;17(1):59-67.