“Handle the chemicals with utmost care” –I still remember the words of my chemistry teacher from my school days. Our science students are well versed with the various chemistry experiments right from their school days. Being science teachers we caution them to be very careful in the labs and not to mess up with the chemicals, most of them as we know are toxic in nature. But is it that they are always toxic in nature or toxic above a certain concentration? That’s when the question pops up –How much is too much? Toxicity indicates how poisonous a substance is to biological organisms.
It’s a very common saying that the dose makes the poison. Many substances that we thought were harmless turn out to be toxic at a higher concentration.
Which would you prefer to drink—a cup of caffeine or a cup of trichloroethylene? Obviously the answer would be “caffeine.” Caffeine occurs naturally in coffee, tea, and chocolate. On the other hand Trichloroethylene is a common ingredient in glues, paint removers, and cleaning fluids. So, which would be better to drink? Believe it or not, caffeine is more poisonous than trichloroethylene, Caffeine at low concentrations acts as a stimulant. Asians are found to consume a larger volume of coffee, which contains low concentrations of caffeine, whereas Europeans on the other hand consume high dose of caffeine in tiny coffee cups. The latter is found to have quick results with respect to keeping a person wide awake for hours. At concentrations higher than those found in food products, caffeine can cause insomnia, dizziness, headaches, vomiting, and heart problems. Research reports show that high doses of caffeine have caused birth defects and cancer.
Even water can kill you if you drink too much too quickly. All it means is that many common substances found in food and drinks are toxic if you eat or drink large enough quantities. The amount of caffeine in a normal human diet does not cause illness, but just 50 times this amount is enough to be fatal. Trichloroethylene is less toxic over the short term than caffeine, but it is not harmless. In fact, long-term exposure may cause a variety of health problems, including cancer as well as damage to liver and kidneys.
In the early 1500's, a Swiss doctor named Philippus Aureolus Theophrastus Bombastus von Hohenheim-Paracelsus wrote: All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy. He was one of the first people to recognize that a chemical can be harmless or even beneficial at low concentrations but poisonous at higher doses. That’s why doctors insist on taking medicines in the right dosage. For example, vitamin D is an important nutrient, but taking more than the recommended dose can cause serious health problems, including kidney stones, high blood pressure, deafness, and even death.
Do we need to really worry about natural chemicals? They seem to be safer than artificial or synthetic chemicals. We manufacture synthetic compounds to use in a wide variety of products such as cleaners, deodorants, food additives, and pesticides. It is true that some synthetic chemicals cause cancer, and others are highly toxic. But it is also true that many synthetic chemicals are harmless at doses normally encountered in food, water, air, and other sources. Natural chemicals range from relatively harmless to highly toxic. Some plants and animals create toxic chemicals called toxins, either for self-defence or for assistance in catching their prey. For example, rattlesnakes, scorpions, etc., produce natural toxins that are hazardous to humans as well as to other organisms.
Scientists carry out a “dose/response” study in order to evaluate a chemical’s short-term toxicity. The word ‘dose’ refers to the total amount of a substance to which an individual is exposed through the mouth, lungs, or skin. The total dose of a chemical includes the amount of the chemical that is consumed either as itself directly or is contained in food or drinks, the amount that is being inhaled along with the air, and which gets absorbed through the skin, etc.
Exposure to a toxic chemical can be either intentional or unintentional- a smoker intentionally inhales whatever substances are contained in cigarette smoke, whereas nearby people get exposed unintentionally when they inhale second-hand smoke. The word ‘response’ refers to the changes in living things caused by exposure to a specific chemical. Typically, the higher the concentration of a toxic compound, the more powerful is the effect. Scientists study this relationship by carrying out dose/response experiments to determine the response of laboratory organisms to various doses of a test chemical.
Dose/response experiments that are carried out on test organisms are called ‘bioassays’. For each chemical, there is an intermediate range in which some individuals will be affected and others will not. In a typical dose/response bioassay, laboratory rats are fed a single dose of the chemical being tested. Some rats get an extremely high dose, and others receive doses ranging from moderate to very low. Exposure to the chemical occurs on the first day itself, but the experiment continues for 14 days in order to give the organisms’ enough time to response. At the end of this period, scientists count the number of dead rats and note any health-related responses in those that are still alive. At the highest dose, it is likely that all of the rats will be dead. At the lowest dose, most of the rats probably will survive. If the experiment has been properly designed, there should be several doses that have killed some, but not all, of the exposed rats. The end result is a number called the LD50, which stands for the lethal dose for 50% of the treated organisms. In other words, half of the rats that received the LD50 dose have died by the end of the 14-day test period. LD50s are expressed in terms of milligrams of the chemical per kilogram of body weight (mg/kg).
A cup of coffee at bedtime may have no effect on one person, yet may keep someone else awake through the whole night. Toxicity tests are based on group responses. The more individuals tested, the better the chance of accurately estimating the LD50 and of identifying low doses to which only the most sensitive individuals respond.
The more toxic the compound, the lower its LD 50. That makes sense if you think of poisons—the more poisonous a chemical is, the less it takes to kill you. For caffeine, the LD50 is roughly 200 mg in laboratory rats. For trichloroethylene, it is over 7,000 mg. This means that on average, rats can survive eating over 35 times as much pure trichloroethylene as caffeine. (This is a 14-day test and does not consider possible long-term impacts on health and survival).
For some compounds, there is a big difference in LD50 values from one species to another. Dioxin is a good example. The LD 50 for dioxin is 5,000 times higher for hamsters than for guinea pigs. There are several factors which determine how sensitive a species is towards a particular chemical. The rate at which it gets metabolized and gets absorbed into the animal’s blood, or stored in its liver, kidneys, or other tissues varies from species to species. For example, a human being would have a hard time dying from eating too much chocolate. This is not true for dogs—eating just a few chocolate bars can be fatal for dogs because they cannot digest and break down the chemicals in chocolate in the same way as humans do.
Most of the previous examples on toxicity are based on acute toxicity, i.e., the effects on single exposure. Even LD 50 experiments are designed in order to assess the short term response of test organisms to a single dose of chemicals.
For some chemicals, the same total dose can be either deadly or harmless, depending on the rate of exposure. Lead is an example of a chemical that builds up in our bodies over time rather than getting broken down or excreted. Lead poisoning has been linked with stunted growth and mental retardation in children. These are not sudden effects, but ones that develop gradually with long-term, low-level exposures to lead in air, food, and drinking water. Children living in homes with lead paint receive additional doses when they eat chips of paint or breathe dust-filled air. Even though the daily doses may be quite low, lead slowly accumulates in bones. When the concentrations become too high, lead poisoning damages the nervous system and kidneys, causing problems such as hearing loss and mental retardation.
Alcoholic drinks work the same way. A person who drinks too many drinks in a short period of time may die from acute alcohol poisoning. At the rate of only one drink per day, that same total amount of alcohol might do little or no harm. At this slower rate, most people’s livers would have time to break down the alcohol rather than allowing it to build up to harmful levels in the body.
Within limits, our bodies can break down or get rid of many types of toxic compounds before they harm our health. In recent years, people have become increasingly concerned about the effects of long-term exposure to relatively low doses of contaminants. With a healthy lifestyle let’s all convert our surroundings to a less toxic one.
- Meek M, Boobis A, Cote I, Dellarco V, Fotakis G, Munn S, Seed J, Vickers C: New developments in the evolution and application of the WHO/IPCS framework on mode of action/species concordance analysis. J Appl Toxicol 2013, 34:1– 18.
- Slikker Jr W, Andersen M, Bogdanffy M, Bus J, Cohen S, Conolly R, David R, Doerrer N, Dorman D, Gayloy D, Hattis D, Rogers J, Setzer R, Swenberg J, Wallace K: Dose-dependent transitions in mechanisms of toxicity. Toxicol Appl Pharmacol , 2004, 201:203– 225.
- . Slikker Jr W, Andersen M, Bogdanffy M, Bus J, Cohen S, Conolly R, David R, Doerrer N, Dorman D, Gaylor D, Hattis D, Rogers J, Setzer R, Swenberg J, Wallace K: Dose-dependent transitions in mechanisms of toxicity: case studies. Toxicol Appl Pharmacol 2004, 201:226– 294.
- Saghir S, Bartels M, Rick D, McCoy A, Rasoulpour R, Ellis- Hutchings R, Marty M, Terry C, Bailey J, Billington R, Bus J: Assessment of diurnal systemic dose of agrochemicals in regulatory toxicity testing – an integrated approach without additional animal use. Regul Toxicol Phar macol 2012, 63: 321– 332.