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Fact and Fiction

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Fiction #1: 'You'd have to drink 500 bathtubs to get a dose that caused any harm in animal studies.'


There are a number of reasons that this statement is not true:

  • It's not just the dose, it's the timing. Low doses of certain chemicals at specific days of fetal development can cause permanent problems that often only manifest later in life. The same dose at a different time may have no measurable effect at all.
  • Tiny doses are often toxic to some people. Recent EPA funded research found that some people are 10,000 times more sensitive than the average (median) person to certain forms of air pollution (Hattis 2001).
  • We are all exposed to mixtures of hundreds of chemicals, and no one knows the dangers of these mixtures in our blood. Not only that, no one can ever know. To test just 100 chemicals in combinations of 3 would require 162,000 tests. And that is just for one effect, say cancer. For nervous system toxicity, it would take another 162,000. For endocrine effects, yet another 162,000. And so on.
  • Sometimes low doses are more toxic than high doses, yet this type of study is almost never conducted. Low dose toxicity appears especially true for chemicals that effect the endocrine (hormone) system. In one recent study an estrogenic chemical caused enlarged prostates in rats at 2 ppb, but had the opposite effect at 200 ppb (Welshons et al 1999). A study with common pyrethroid insecticides induced hyperactivity in rats at doses up to 0.7 mg/kg but no hyperactivity at a dose 60 times higher (42 mg/kg) (Schettler et al 2000, pg 83). The reason appears to be that at higher doses defense mechanisms kick in. Health effects linked to low dose chemical exposures in animals (but not found at high doses) include increased prostate size, premature onset of cyclicity (menstruation), increased uterine weight, and hypersensitive immune system responses (vom Saal et al 1997, vom Saal et al 1995, Gray et al 1989, Halling and Forsberg 1993, Fan et al 1996). Industry almost never does tests to determine low dose effects, so when they say low doses cause no effects in animals, it is almost always because they haven't looked.
  • People are often more sensitive to toxic substances than test animals. Animal tests missed the toxic dose of PCB's by 10,000 times (Rice et al 1996). The dose that caused permanent loss of IQ was only found through tracking of injured children. In another recent survey, humans were shown to be up to 200 times more sensitive than animals to 21 chemicals known to cause birth defects (Klaassen 1996).
  • Chemicals are almost never studied for toxic effects at low doses. Animal tests are conducted at high doses for reasons of statistical power. This bias, while necessary, has created a dearth of knowledge of possible low dose effects, particularly on systems known to be sensitive to well-timed tiny doses of chemicals, such as the developing brain, nervous system, and endocrine (hormone) system.
  • Low dose effects can be easily missed by standard high dose animal studies (assuming that the tests have been done at all). A low dose effect that occurs in just one out of every 1,000 people could be missed completely by animal studies which use only 500 animals at relatively high doses. An effect that occurred in 1 in 1,000 people would injure 270,000 people in the U.S. population.

Humans are effected by low doses of chemicals.

  • It takes just 40 parts per billion (the equivalent of 1 drop in 15 bathtubs of water) of the hormone MIS to produce male sexual organs in the human embryo (Josso 1993). Put another way, it takes 40 ppb of MIS to terminate vaginal development in an embryo, the seminal event in the development of a male instead of a female child.
  • PCBs at just 5 parts per billion in maternal blood during fetal development can cause adverse brain development, and attention and IQ deficits that appear to be permanent (Schettler et al. 2000). Five parts per billion is equivalent to one drop of water in 118 bathtubs.
  • Dioxin causes a significant change in the sex ratio of children born to men who have just 80 parts per trillion of the chemical in their blood (Mocarelli 1996 & 2000). Men father nearly twice as many girls as boys when their blood levels of dioxin reach the equivalent of just one-drop of dioxin in 7,400 bathtubs.
  • Low doses of lead cause learning deficits in children, but the same dose has no effect on adults. Just 10 mg per deciliter, or 100 ppb (the equivalent of 1 drop in 6 bathtubs) in the blood of a two year old can cause a significant decrease in IQ in adolescence and adulthood (CDC 1997).
  • A 5/1,000ths ounce chip of lead paint can put child in the emergency room with lead poisoning (Calculated based on CDC 1997 & EPA 1998).
  • And while it not a toxic effect, our sense of smell illustrates the exquisite sensitivity of the human brain. People can detect maple furanone at 1 part per quadrillion, or one drop in 590 million bathtubs of water (Leffingwell 1991).

References

Fan F, D Wierda, KK Rozman. 1996. Effects of 2,3,7,8-tetrachlorodizenzo-p-dioxin on humoral and cell-mediated immunity in Sprague-Dawley rats. Toxicology 106(1-3):221-228.

Gray LE, J Ostby, J Ferrell, G Rehnberg, R Linder, R Cooper, J Goldman, V Slott, J Laskey. 1989. A dose-response analysis of methoxychlor-induced alterations of reproductive development and function in the rat. Fundam. Appl. Toxicol. 12:92-108.

Halling A, JG Forsberg. 1993. Acute and permanent growth effects in the mouse uterus after neonatal treatment with estrogens. Reprod. Toxicol. 7(2):137-153.

Hattis, D, et al., 2001, Human interindividual variability in susceptibility to airborne particles, Risk Analysis, in press.

Josso, N, et al., 1993, Anit-Mullerian hormone: the Jost factor, Recent Progress in Hormone Research, 48, 1-60.

Klassen, CD, ed. 1996. Casarrett & Doull's Toxicology. The Basic Science of Poisons. Fifth ed. The McGraw-Hill Companies, Inc.

Leffingwell, J and D Leffingwell, 1991, GRAS flavor chemicals - detection thresholds, Perfumer & Flavorist, 16, 3-19.

Mocarelli P, P Brambilla, P Gerthoux, et al., 1996, Change in sex ratio with exposure to dioxin [letter], The Lancet 348, 409.

Mocarelli, P, et al., 2000, Paternal concentrations of dioxin and sex ratio of offspring, The Lancet, 355, 1858-1863.

Rice D., A. Evangelista de Duffard, R. Duffard, et al., 1996, Lessons for neurotoxicology from selected model compounds: SGOMSEC joint report, Environ. Health Perspect., 104, 205-215.

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.

US Centers for Disease Control and Prevention, 1997, Facts on Lead, http://www.cdc.gov/nceh/lead/guide/1997/docs/factlead.htm.

US Environmental Protection Agency, 1998, Risk Analysis to Support Standards for Lead in Paint, Dust, and Soil: Volume 1, EPA 747-R-97-006.

Vom Saal FS, BG Timms, MM Montano, P Palanza, KA Thayer, SC Nagel, MD Dhar, VK Ganjam, S Parmigiani, WV Welshons. 1997. Prostate enlargement in mice due to fetal exposure to low doses of estradiol and diethylstilbestrol and opposite effects at high doses. Proc. Natl. Acad. Sci. USA 94:2056-2061.

Vom Saal FS, SC Nagel, P Palanza, M Boechloer, S Parmigianai, WV Welshons. 1995. Estrogenic pesticides: Binding relative to estradiol in MCF-7 cells and effects of exposure during fetal life on subsequent territorial behaviour in male mice. Toxicol. Lett. 77:343-350.

Welshons W, SC Nagel, KA Thayer, BM Judy, FS vom Saal. 1999. Low-dose bioactivity of xenoestrogens in animals: fetal exposure to low doses of methoxychlor and other xenoestrogens increases adult prostate size in mice. Toxicol Ind Health 15(1-2):12-15.

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last updated: march.27.2009

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