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Fact #2: People vary enormously in their reaction to toxic substances


People are incredibly different in their reactions to chemicals, allergens, drugs, diseases and a host of external stimuli. That's why the government applies safety factors to the results of animal studies when they set safe exposure limits for pollutants or contaminants in food and water. Often, however, these safety factors are not enough to protect large numbers of sensitive people.

Many factors determine how a drug, allergen, or toxic substance will affect a person - genetics, metabolism, age, sex, size, disease, diet, and environment. (Gibson and Skett, 1994). The result is vast variability in the human response to chemicals, viruses, drugs and a host of substances (up to 100,000 fold differences), most of which is influenced by factors that individuals cannot control.

Allergies

There are enormous differences between sensitive and 'immune' populations in their reaction to common allergens. Some common food allergies powerfully illustrate the point. Peanut butter can easily kill people who are allergic to it, while those who are not can eat as much as they can stand, with no effects at all. At least three people have died from peanut allergy using a knife that had been 'wiped' after making a peanut butter sandwich. About 6 tenths of one percent of the U.S. population (2 million people) is allergic to peanuts. (Sampson 2001) The same phenomenon occurs with non-lethal allergies. A recent EPA sponsored review found that sensitive individuals are up to 450 times more sensitive than the median (average) person to common allergens like ragweed and wheat flour. (Hattis 2001).

Genetic differences

The recently completed map of the human genome has revealed the tremendous genetic variability in the human population. Scientists have identified an estimated 1.4 million specific differences, or polymorphisms, in the human genetic code. Every polymorphism on a human gene is a DNA sequence that differs from one person to the next. Each of these 1.4 million polymorphisms represents a chance for a person to be at risk for a particular disease or uniquely susceptible to the harmful effects of a particular chemical (Stoneking 2001). Put another way, there are now truly 1 million ways that a person could be more or less sensitive to toxic chemicals than his or her neighbor.

Metabolism

Differences in metabolism dramatically influence the toxicity or effectiveness of chemicals and drugs. Metabolism is a function of genetically determined factors including race, age, sex,, and inherent variability (polymorphisms) as well as external factors like diet, disease-state, and exposure to chemical pollutants and heavy metals. One well-characterized genetic variable is the difference in critical metabolic enzyme levels. From 3 to 10 percent of Caucasians "do not have" or "have either low or no activity" of the enzyme (CYP2D6) that metabolizes codeine and the prescribed tricyclic antidepressants (Richelson 1997). Poor functioning, but normally occurring enzyme levels can also make individuals far more vulnerable to toxic chemical exposure. About 30 percent of the population carries a poor version of the enzyme paraoxonase which makes them 11 times more vulnerable to certain neurotoxic insecticides than people with fully functioning paraoxonase (Schettler 2000).

Natural Immunity

Individuals with a 'natural' immunity to typhoid fever are 10,000 times more resistant to the disease than the average person. These people show no symptoms when exposed to 1 billion viable salmonella typhosa organisms, whereas some people get the disease after exposure to just 10,000. (Hornwick 1970) Similarly, people with a 'natural' immunity to rotavirus (a virus causing diarrheal disease in infants and young children) are 100,000 times more resistant than the weakest person (Ward, et al. 1986). These are just two examples of the obvious fact that peoples' immune systems are enormously different, often in ways that are little understood by scientists.

Chemical absorption

Absorption in the gut may vary by orders of magnitude. While some people who eat mercury contaminated fish absorb 13% of the mercury from their stomach into their blood, others only absorb only 1% (Stern 1997). This means that if two pregnant women eat the same amount of mercury in a fish, one could deliver ten times more mercury to the brain of her developing child.

References

Gibson, G. and P. Skett, 1994, "Chapter 4: Factors affecting drug metabolism: internal factors," in Introduction to drug metabolism, London: Blackie Academic & Professional.

Hattis, D., A. Russ, R. Goble, et al., 2001, Human interindividual variability in susceptibility to airborne particles, submitted to Risk Analysis.

Hornwick, R., S. Greisman, T. Woodward, et al., 1970, Typhoid fever: pathogenesis and immunologic control, N. Eng. J. Med., 283, 686-691.

Richelson, E., 1997, Pharmacokinetic drug interactions of new antidepressants: a review of the effects on the metabolism of other drugs, Mayo Clin. Proc., 72, 835-847.

Sampson, H., 2001, Personal correspondence via email.

Schettler T, J Stein, F Reich, M Valenti. 2000. In Harm's Way: Toxic Threats to Child Development. Greater Boston Physicians for Social Responsibility. May 2000.

Stern, Alan H. 1997. Estimation of the interindividual variability in the one-compartment pharmacokinetic model for methylmercury: Implications for the derivation of a Reference Dose. Regulatory Toxicology and Pharmacology. 25. 277-288.

Stoneking M., 2001. Single nucleotide polymorphisms: from the evolutionary past . . . Nature. 409. 15 February 2001.

Ward, R., D. Bernstein, E. Young, et al., 1986, Human rotavirus studies in volunteers: determination of infectious dose and serological response to infection, J. Infect. Disease, 154, 871-880.

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last updated: march.27.2009

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