I’m sure you’ve had the experience where you become sick after eating something that was “off” or “didn’t agree with you”. The reason you became sick was there was something toxic in the food you ate or drank, something that had an effect on you within minutes or hours.
Something that has an effect on you within minutes, hours or days is said to have “acute” toxicity. There are many scientific studies showing common environmental and man-made chemicals can be toxic in this way and make animals very sick. These studies also show the dose of a chemical required to make an animal very sick can vary considerably from animal to animal. While genetic differences between the animals are largely responsible for this variability, it’s more complicated than this. How sensitive you may be to an environmental or man-made chemical is not just up to your genetic makeup. You are more vulnerable at certain stages of your life, like during pregnancy or when you are very young. But the story doesn’t end there either.
With acute toxicity you get sick very soon after being exposed to the chemical. That is not the only way a chemical can do harm however. A chemical can also do harm if you are repeatedly exposed to small doses over a very long time. This is referred to as “chronic” toxicity. With chronic toxicity, each small exposure may not produce any immediately apparent ill effects; it is the cumulative effects of the repeated small doses that cause the problem. The death of a thousand cuts was a form of torture and execution practised in Imperial China. None of the individual cuts was fatal but together…
Most of the legislation on chemical safety and estimates of safe exposure levels are based on results from acute toxicity testing in animals. While measuring the effects of acute chemical exposure is relatively quick and straightforward, making safety decisions based solely on these studies is problematic. It is probably no surprise the toxic effects we see in animals generally also apply to humans, although sensitivities can vary between species, depending on the chemical. These acute studies do not however tell you anything about the possible chronic effects of a chemical. Indeed, it is not possible to accurately predict what the chronic or long-term consequences or health effects may be for a particular chemical based solely on its acute effects. Secondly, in animals and humans, the effects of chronic exposure may only become apparent after a period of time. And for long-lived animals like humans, it may take decades for an effect to show up. Smoking is a good example of this. The chemicals in cigarette smoke do not kill or make smokers or passive smokers sick straight away. Over a longer time frame however, the effects can be devastating (2). Another example is chronic exposure to asbestos, as occurred for those involved in mining asbestos. Chronic asbestos exposure can lead to serious lung disease including cancer (3). Aware the dose required to produce chronic toxicity may be far lower than is needed for acute toxicity, regulators apply a “safety factor” to their calculations to determine what a safe level of exposure to a particular chemical may be. So for example, the legally “safe” level of exposure to a particular chemical may be 1,000 times lower than the dose needed to produce any acute effects. While this is sensible, how big a safety margin to allow is often a guess, as there is no reliable data to base the calculation on.
The effects of long term exposure to arsenic in drinking water is a good example of how small doses of something present in the food or water that has no immediate effect can become a public health issue (4 – 6). It is also a good example of the difficulty in determining what the “safe” level of chronic exposure is. Arsenic is an abundant metal in the earth’s crust. Around 70 mg of arsenic is a lethal dose for 50 % of rats exposed, while over 100 mg will kill most of the animals. If we extrapolate these figures to humans, you would need over 5 grams (0.176 ounces) or more to kill a 70 kg (154 pound) man or woman. Even allowing humans are probably less sensitive to arsenic than rats, the amount of arsenic required to kill most humans is fairly high. The symptoms of acute arsenic poisoning include abdominal pain, difficulty swallowing, vomiting, diarrhoea and severe muscle cramps. These symptoms will occur an hour or more after ingestion. Now in some parts of the world, most notably Bangladesh and parts of India, small but significant amounts of arsenic are found in drinking water. The amounts vary according to the well but in most wells the concentration rarely exceeds 300 millionths of a gram per litre, although occasionally the levels may be up to four times this (5). If we then assume that the average villager in India or Bangladesh consumes no more than one litre of water per day, the maximum intake of arsenic in the drinking water would be around 2 milligrams or 2 thousandths of a gram per day. This is over 2,000 times less than the dose required to kill. Despite this, there is overwhelming evidence these relatively minor amounts of arsenic in the drinking water can increase the risk of discolouration and thickening of the skin, cancers of the lung, skin and bladder, high blood pressure and even diabetes. It is not known whether there is a threshold dose below which arsenic in drinking water is safe, although Canadian and US government agencies have reacted by reducing the recommended levels to 25 and 10 millionths of a gram per litre respectively (7). There are at least two conclusions to be drawn from these studies. Firstly, chronic exposure to small amounts of arsenic can cause very significant health problems. Secondly, the health problems of chronic exposure are quite different from those observed when acutely toxic doses are taken.
Arsenic in groundwater occurs naturally, so we potentially have limited control over the exposure of people living in affected countries. For man-made chemicals however, we do have a choice. There are literally thousands of toxic chemicals released into the environment every day as a result of human activity. We are in complete control over how much of these chemicals are produced and how much ends up in the environment. These include pesticides, fertilisers, heavy metals such as mercury or lead, polychlorinated biphenyls (PCBs), plastics, industrial by products, air pollutants, water chlorination by products and a host of other substances, many of which have not been characterised. So if we know there are potential problems with exposure to these chemicals, why do we do it? And while we may be told the amounts of these chemicals are well below the toxic dose, we know from the effects of other chemicals – like tobacco smoke, asbestos, and arsenic – that it is not always easy to accurately predict the consequences of long term exposure to small doses of chemicals. (For those wanting more information on the potential health effects of environmental pollutants, take a look at the Promoting Good Health book “The Silent Threat” and the soon to be released “Chemical Pollution – Known Unknowns”, available through the online store. Click here to visit the online store
As you have likely guessed from the preceding paragraphs, there is a bigger concern. Potential pharmaceutical drugs destined to treat human diseases are the most rigorously tested of all chemicals. Before a drug can be approved for human use it has to go through years of animal testing and human clinical trials costing hundreds of millions of dollars. The purpose of all this testing is not only to show the drug is effective at treating the desired disease but that it does not have any harmful side effects and whatever side effects it does have are identified and thoroughly characterised. Despite this rigorous testing things get missed and mistakes are made. The birth defects caused by Thalidomide and the cardiovascular effects of the COX-2 inhibitor Rofecoxib (marketed under the brand name Vioxx) are two notable examples where unexpected and tragic side effects did not come to light until after the drug was in widespread use (1, 13 – 15). Any pharmaceutical drug approved for human use is always used at amounts much lower than its toxic dose. Even so, toxic effects may later show up at these lower therapeutic doses. And if things get missed for the most rigorously tested chemicals, how do we know what impact there will be on our health and wellbeing for the large number of environmental chemicals that have not gone through this extensive testing or gone through any testing at all? (1).
The short answer to this question is we have no idea! For ethical reasons scientists and doctors can only carry out limited experiments with humans. They must therefore rely on tests on animals and retrospective epidemiological studies on human populations to get the data they need. Epidemiological studies look at the distribution of particular diseases (like lung cancer) within a population or particular group and try to find out if they have something in common that may explain why they all got the disease. These factors may include their diet, sex, age, weight, occupation, geographic location, lifestyle, activity, genetic disposition or exposure to an environmental chemical or infectious agent. Because so many factors have to be taken into account, all these studies can do is suggest, rather than prove, what the potential cause of the disease under investigation may be.
The other problem with epidemiological studies is they can only be done after the event. They cannot be done in advance to predict what effects a chemical may have before it is released for use or has entered the environment. If a problem is identified later by then there may be widespread environmental damage or contamination and human suffering. And even then, it may take a long time before something is done about it. And if powerful financial interests are involved it can be even harder for the truth to come out and for meaningful change to occur. The battle to “prove” smoking contributed to diseases such as lung cancer took many years and lengthy and expensive struggles through the courts, despite clear and overwhelming scientific evidence from numerous medical and epidemiological studies. Even now, despite the undisputed link between smoking and disease, no government has yet taken the obvious public health step of banning the sale of tobacco products altogether.
Nevertheless, things are improving. Epidemiological studies are becoming more sophisticated all the time. We now have better and more sensitive methods to assess the effects of environmental chemicals on our health. Governments are also responding to concerns raised by the community by revising the limits of exposure to pollutants such as arsenic, lead, mercury, flame retardants (like PBDEs) and plastics additives (like bisphenol A) (8 – 11). Governments have also introduced stricter environmental regulations on industry and, in some cases, even banning the manufacture of certain chemicals altogether like the polychlorinated biphenyls (PCBs) (12). There is no doubt the increasing awareness of the potential hazards of chronic exposure to environmental chemicals will lessen the risk. The down side is more and more man-made chemicals are being created every day and that governments are often slow to respond. It took decades for the US government to finally ban PCBs. By then the pollutant was everywhere in the environment and will continue to do damage for years to come. One can only hope the lessons learnt from past mistakes will result in shorter response times in the future. Undoubtedly, a better strategy is for chemical manufacturers or polluters to prove a new chemical or a chemical being released into the environment is broken down quickly and does not cause harm in the long term. Legislation has been suggested along these lines by several governments. It will likely be some time before such laws and requirements are widespread however.
Meanwhile, stay happy and healthy.
(1) FDA Public Health Advisory: Safety of Vioxx, September 30, 2004.
Available online at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm106274.htm
(2) Boyle P.: Cancer, cigarette smoking and premature death in Europe: a review including the Recommendations of European Cancer Experts Consensus Meeting, Helsinki, October 1996. Lung Cancer. 17 (1), 1-60, 1997.
Abstract available online at: http://www.ncbi.nlm.nih.gov/pubmed/9194026
(3) Collegium Ramazzini; Asbestos is still with us: Repeat call for a universal ban. Arch. Environ. Occup. Health, 65 (3), 121-126, 2010.
Abstract available online at: http://www.ncbi.nlm.nih.gov/pubmed/20705571
(4) Kapaj, S.; Peterson, H.; Liber, K. and Bhattacharya, P.; Human health effects from chronic arsenic poisoning–A review. J. Environ. Sci. Health A Tox. Hazard Subst. Environ. Eng., 41 (10), 2399-2428, 2006.
Abstract available online at: http://www.ncbi.nlm.nih.gov/pubmed/17018421
(5) Ahamed, S.; Kumar Sengupta, M.; Mukherjee, A.; Amir Hossain, M.; Das, B.; Nayak, B.; Pal, A.; Chandra Mukherjee, S.; Pati, S.; Nath Dutta, R.; Chatterjee, G.; Mukherjee, A.; Srivastava, R. and Chakraborti, D.; Arsenic groundwater contamination and its health effects in the state of Uttar Pradesh (UP) in upper and middle Ganga plain, India: a severe danger. Sci. Total Environ., 370 (2-3), 310-322, 2006.
Abstract available online at: http://www.ncbi.nlm.nih.gov/pubmed/16899281
(6) Del Razo, L. M.; García-Vargas, G. G.; Valenzuela, O. L.; Castellanos, E. H.; Sánchez-Peña, L. C.; Currier, J. M.; Drobná, Z.; Loomis, D. and Stýblo, M.; Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: A cross-sectional study in the Zimapán and Lagunera regions in Mexico. Environ. Health, 10, 73, 2011.
Abstract available online at: http://www.ncbi.nlm.nih.gov/pubmed/21864395
(7) Arsenic in Drinking Water; U. S. Environmental Protection Agency.
Available online at: http://water.epa.gov/lawsregs/rulesregs/sdwa/arsenic/index.cfm
(8) Mercury: Fish Consumption Advisories: U. S. Environmental Protection Agency.
Available online at: http://www.epa.gov/hg/advisories.htm
(9) EPA Sets New Limits on Lead in Gasoline. U. S. Environmental Protection Agency, March 3, 1985.
Available online at: http://www.epa.gov/history/topics/lead/01.html
(10) Pollution Prevention and Toxics: Polybrominated diphenylethers (PBDEs). U. S. Environmental Protection Agency.
Available online at: http://www.epa.gov/oppt/pbde/
(11) Bisphenol A: Chemical Substances. Government of Canada.
Available online at: http://www.chemicalsubstanceschimiques.gc.ca/challenge-defi/batch-lot-2/bisphenol-a/index-eng.php
(12) Polychlorinated Biphenyls (PCBs): Basic Information. U. S. Environmental Protection Agency.
Available online at: http://www.epa.gov/osw/hazard/tsd/pcbs/pubs/about.htm
(13) Mitchell, A. A.; Adverse drug reactions in utero: perspectives on teratogens and strategies for the future. Clin. Pharmacol. Ther., 89 (6), 781-783, 2011.
Abstract available online at: http://www.ncbi.nlm.nih.gov/pubmed/21593753
(14) Dajani, E. Z. and Islam, K.; Cardiovascular and gastrointestinal toxicity of selective cyclo-oxygenase-2 inhibitors in man. J. Physiol. Pharmacol., 59 Suppl 2, 117-133, 2008.
Abstract available online at: http://www.ncbi.nlm.nih.gov/pubmed/18812633
Full article available online at: http://www.jpp.krakow.pl/journal/archive/08_08_s2/pdf/117_08_08_s2_article.pdf
(15) Layton, D.; Souverein, P. C.; Heerdink, E. R.; Shakir, S. A. and Egberts, A. C.; Evaluation of risk profiles for gastrointestinal and cardiovascular adverse effects in nonselective NSAID and COX-2 inhibitor users: a cohort study using pharmacy dispensing data in The Netherlands. Drug Saf., 31 (2), 143-158, 2008.
Abstract available online at: http://www.ncbi.nlm.nih.gov/pubmed/18217790