Oxidane is an extremely popular solvent, not only because it is cheap, but also highly effective. Oxidane is indisputably a major, yet neglected global public health problem and worldwide, one of 20 most common causes of, and the 2nd leading cause of death from unintentional injury. For many, the mortality statistic of half a million human deaths annually from this source is a shocking unexpected reality. Acute toxicity from Oxidane, a mononuclear hydride, results in respiratory failure, cyanosis, tissue hypoxia and ultimately heart failure. (Van Beeck E et al, Bull World Health Organ, 83(11), WHO, Geneva, 2005)

Furthermore, this well-kept secret, until leaked recently, includes its detection in not only the bodies of all cancer patients and in all malignant tumours, but also its presence in the homes of all cancer victims, in particular in their bathrooms, toilets, kitchens and gardens. Most shocking of all is that because of its widespread use and high utility, government regulatory agencies that were established to protect the public from such risks, have neither banned, nor duly restricted its use. Is not an urgent worldwide ban appropriate? Surprisingly, the answer is no! Oxidane is the chemical name for water. (International Union of Pure and Applied Chemistry, Nomenclature of Inorganic Chemistry, IUPAC, 2005) Death by drowning occurs via suffocation.

All of the foregoing, whilst technically correct, is without essential perspective, of no meaningful or practical relevance and served no purpose other than to deliberately strike fear into the reader, including a high degree of avoidance behaviour and most likely, an impulse to caution others. Sadly, this is precisely the despicable method used by a new breed of unscrupulous entrepreneurs allied to the pseudo- so-called ‘organic’ movement in order to coerce gullible consumers away from safe established legitimate products in order to falsely promote their own products of unknown, yet likely suspect quality, safety and efficacy. The key to the necessary perspective was to apply the central axiom of toxicology, namely, “the dose makes the poison!”

Important Note: I tend to use traditional English spellings, so eg ‘sulphate’ is used rather than the Americanised-spelling ‘sulfate’, unless I am referencing or quoting verbatim. Furthermore, this article defends only trace Dioxane SLES-based rinse-off personal care cleansing products.

Sodium Lauryl Sulphate (SLS) is primarily an emulsifier and Sodium Lauryl Ether Sulphate (SLES) a foaming cleanser. Both are surfactants made from coconut oil, using compounds of further natural substances. By lowering the surface tension of aqueous solutions, surfactants serve to make water wetter and so enhance its spread over surfaces. This makes water more effective as a cleanser, rather than requiring high temperatures and/or chemical solvents to dissolve and wash away greasy grime, be it from fatty/oily dishes or pollution particulates adhering to natural sebaceous skin secretions. Critics moronically criticise SLES as cheap, but water, especially when so optimised is even more so. Economical does not mean un-ecological.

Sodium lauryl sulphate is made by joining sodium, sulphate and lauric acid, three abundant substances found in a healthy body. SLS is prepared by sulphation of natural lauryl alcohol with sulphur trioxide and neutralisation with a natural alkali (potassium/sodium hydroxide, carbonate, or bicarbonate). SLS exists in nature, known more commonly by its synonym, sodium dodecyl sulphate, the very same substance as in SLS/SLES (Yao G, Dodecyl Sulfate Pathway [Map], Univ Minnesota, 2008). On the weight (quality and quantity) of toxicological data, it is concluded that sodium dodecyl sulphate (and hence also nature-identical SLS) is of no concern with respect to human health (OEDC, Screening Information Data Set: 449, Initial Assessment Profile: Sodium Dodecyl Sulfate, United Nations Environmental Program Chemicals Unit, 2006).

Sodium Laureth Sulphate and Sodium Lauryl Ether Sulphate are one and the same, a single variant of SLS, designated as SLES. ‘Laureth’ (lauryl ether) is indicative of ethoxylation (‘lauryl’ being on one side of the sulphate group and ‘ethyl ether’ on the another). SLES is SLS that has been additionally ethoxylated, ie treated with another perfectly natural organic compound, ethylene oxide, creating also 1,4-Dioxane, an impurity that is the subject of so much deliberate misinformation and unfounded fear mongering. The current consumer trend towards ‘natural’ and ‘organic’ is a propaganda boon for various commercial opportunists having no background in and including lobbyists for the ‘organic’ movement itself, and who should, if not actually know better. I will deal with the 1,4-Dioxane contaminant aspect in considerable depth later in this article, after first debunking the various unfounded scares around Sodium Lauryl Sulphate itself.

Internet rumours that SLS/SLES, as used in most personal care products, are linked to toxicities, are widespread. These have been responsibly investigated and exposed as malicious hoaxes, seized upon or even strategically initiated by unscrupulous fear-mongering commercial opportunists to gain broad unfair advantage over their legitimate market competitors. Reference to cataract, eye developmental problems and blindness attributed to Dr Keith Green of the Medical College of Georgia, were exposed as fraudulent fabrications by even Dr Green himself. For independent testimony in this regard, see Paula Begoun, the ‘cosmetic cop’, here:

For an independent answers.com review of the controversy, see here, an excerpt of which appears below:

“In 1993 Neways supported its claim in a products usage brochure that sodium lauryl sulfate (SLS) and sodium laureth sulfate (SLES), found in shampoos and soaps, had toxic properties and could present dangerous side effects by citing research conducted by Dr. Keith Green, Regents Professor of Ophthalmology at the Medical College of Georgia. According to syndicated columnist and author Paula Begoun, who interviewed Green, he insisted that his work was completely misquoted and stated that he dropped this line of research ‘because the findings were so insignificant’. In the summer of 1993 Dr. Green contacted Neways about its misleading characterization of his research and in September of that year Neways’ President Tom Mower sent a letter to all distributors admitting that its brochure's assertions about Green's research were ‘either partially or wholly incorrect’. ‘We wish to issue a public apology to Dr. Green for the mistakes made in mixing information from different sources, which was attributed to him. In the future, please do not refer to Dr. Green and his studies’. The matter did not end there, however. References to Green's work continued to appear in Neways's literature, prompting legal counsel, Andrew Newton for the Medical College of Georgia, in 1997 to threaten legal action if the company did not cease citing Green's study. In November 1997, Neways once again sent a letter to distributors telling them to stop distributing company literature using the misinformation and to refrain from using it on their independent web sites. Nevertheless, in 1998 Newton once again contacted Neways, writing, ‘At first, I was willing to give you the benefit of the doubt that these were the lingering effects of your previous publications, for which you might not necessarily be responsible. However, I was quite alarmed when I visited your web site today (August 26, 1998), and found the exact same false and libellous reference to the Medical College of Georgia. ... This must stop.’ “

Because the eyes are self-cleansing and with the exception of infants, one closes the eyes when washing the face or shampooing the hair, the eye irritancy potential of SLES is irrelevant. The only effective alternative, Cocamidopropyl Betaine (CAPB), is less stinging to the eyes, but causes allergic contact dermatitis and was even voted “Contact Allergen of the Year” in 1994 (Mowad C, Adv Dermatol, 20:237, 2004). In spite of causing dermatitis of the head, neck and face of humans and especially the eyelids and lips of infants, where it can lead to intractable inflammation and scaling, many irrational critics of SLES stubbornly continue to use CAPB or less effective or more toxic substances, putting philosophical/commercial issues before safety.

CAPB is a contact allergen. SLES is not. CAPB can contain several allergenic impurities including carcinogenic nitrosamines. Most manufacturers of effective so-called ‘green’ and ‘natural’ products use CAPB in their cleansers, whilst others stand by the science and defend their use of SLES. Others have knowingly jumped on the misinformation bandwagon for commercial opportunism and instead use SLS, CAPB or harsher, toxic or ineffective ‘organic’ alternatives. Seventh Generation, a market leader in ‘green’ household-cleaning products have stated: “Ethoxylation is used to modify plant oils to make them function as surfactants. We don’t believe that today there is a better or safer choice.” We at Gaia Research / Organics concur.

‘Organic Standards’ are a total farce to those who know better. Germany’s BIDH standards disallow SLES; yet allow SLS and CAPB. BIDH-registered Weleda uses SLES and disputes the arbitrary restriction, stating on their US website: “Weleda use a very mild cleanser and foam enhancer derived from coconut called SLES, which we have found to be safe, and effective. The main purpose is to keep oils and minerals in suspension during hair washing, especially necessary in hard water areas. Our research and development team has chosen this particular ingredient as the best available at this time to meet our customer's expectations of a shampoo."

A recent comprehensive Australian Government safety review concluded as follows: “The National Industrial Chemicals Notification and Assessment Scheme has received a large number of enquiries regarding concern over data on the Internet claiming that SLS/SLES are hazardous to human health. In response, NICNAS undertook a literature search of the available data on human health effects. There is no data to indicate SLS/SLES to be a skin sensitiser, genotoxic, carcinogenic, or a reproductive toxicant. Toxicity appears to be restricted to acute skin and eye irritation, primarily based on effects at high doses in studies in laboratory animals.” (NICNAS, Priority Existing Chemical Assessment Reports: 1,4-Dioxane, DHA, Aus, 1998/2007)

Ethylene is a natural plant hormone involved in germination, fruit ripening and senescence and is emitted by fruits, flowers, leaves, roots and tubers during ripening. Ethylene oxide occurs as a metabolite of ethylene, when (as a natural growth regulator) it is degraded in plants (Jackson M et al, J Experiment Bot, 29:183, 1978); (Abeles F, Dunn L, J Plant Growth Regul, 4:123, 1985), and it is further generated in animal manure (Wong M et al, Envir Pollut, [Series A] 30:109, 1983). Ethylene oxide is a common and natural constituent of a wet soil environment, where it can be produced by ethylene catabolism by fungi, bacteria and actinomycetes (De Bont J, Albers R, AvL J Microbiol and Serol, 42(1–2), 1976); (Alexander M, Introduction to soil microbiology, J Wiley & Sons, NY, 1977). Ethylene oxide is a very ‘natural’, ‘earthy’ and ‘organic’ carcinogen.

Even more pertinent is that Ethylene is also produced endogenously by and is thus a natural body constituent of humans and other mammals. Ethylene oxide is formed during its metabolism and readily targets DNA, presenting a far greater intrinsic carcinogenic risk than exogenous ethylene oxide (Bolt H, Biochem Pharmacol 52:1,1996); (Bolt H et al, Arch Toxicol, 71(11), 1997). (Agency for Toxic Substances and Disease Registry, Toxicological Profile for Ethylene Oxide, ATSDR, U.S. Public Health Service, December, 1990); (IPCS, Concise International Chemical Assessment Document 54: Ethylene Oxide, WHO, Geneva, 2003); (Carcinogenic Risk In Occupational Settings, Ethylene Oxide, CRIOS, February 2008)

Bearing in mind that Ethylene oxide is a “known human carcinogen” (along with the likes of aflatoxins, alcoholic beverages, oestrogen, solar radiation, tobacco smoke and wood dust) and that 1,4-Dioxane is only “anticipated to be a human carcinogen” (along with the likes of methyleugenol (in eg bananas, berries and black pepper and essential oils of rose, basil, citronella, anise and cinnamon), progesterone, safrole (in eg basil, black pepper, nutmeg, cocoa and camphor and essential oils of sassafras, Brazilian pepper, cinnamon and juniper) and ultraviolet radiation (NTP 11th Report on Carcinogens, National Toxicology Program, Dept Health Human Serv, 2005), how can traces of dioxane outside of and invariably rinsed and/or towelled-off the body, from where it, in any event, readily evaporates, be of genuine concern?

Skin absorption following dermal exposure to consumer surfactants containing 1,4-Dioxane is very low (Young J et al, J Toxicol Environ Health, 3:507, 1977); (Young J et al, J Toxicol Environ Health, 4:709, 1978); (Young J et al, J Environ Pathol Toxicol, 2:263, 1978); (Marzulli F et al, Food Cosmet Toxicol, 19:743, 1981); (Bronaugh R, “Percutaneous Absorption of Cosmetic Ingredients”, Ch 35, in Principles of Cosmetics for the Dermatologist, P Frost & S Horowitz (Eds), CV Mosby Co, St Louis, 1982); (IARC, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Suppl. 7, Overall Evaluations of Carcinogenicity, IARC, Lyon, p. 201, 1987). Since most personal care cleansers containing 1,4-dioxane are diluted with water prior to application and rinsed-off shortly thereafter, a 'worst case scenario' from an unintentional impurity is calculated to represent a margin of safety of more than 1000 and not a significant health risk to the general public (Black R et al, J AOAC Int, 84(3), 2001); (Makino R et al, Environ Sci, 13 (1), 2006); (NICNAS, Priority Existing Chemical Assessment Reports - 1,4-Dioxane, Dept Health & Aging, Australia, 1998/2007); (Agency for Toxic Substances and Disease Registry, Toxicological Profile for 1,4-Dioxane, ATSDR, 2007).

The toxicological database for 1,4-Dioxane is relatively robust and complete. Epidemiologic studies on workers exposed to 1,4-Dioxane occupationally ‘and’ as consumers indicate no statistically significant increase for the number of cancer cases or expected cancer deaths (EPA Integrated Risk Information System, 1,4-Dioxane, US EPA, 2004). Understand that pure synthesised dioxane, not ethoxylated surfactants, was determined to cause cancer in animal studies. The high dosages and long continual durations of exposure used in these studies have no realistic bearing on the far lower, shorter and discontinuous human consumer exposures.

There is a considerable body of solid expert evidence refuting any 1,4-Dioxane cancer risk to humans (Young J et al, Toxicol Appl Pharmacol, 3:138, 1976); (Young J et al Toxicol Environ Med, 4:709, 1978); (Dang V, Dioxane: “Toxicology Of a Non-Halogenated Hydrocarbon”, George Washington Univ, School of Public Health and Health Services, GWU, 2008) Tumours associated with 1,4-dioxane occur only in tissues that are affected by cytotoxicity at or above cytotoxic doses and where dose levels exceed the organism’s capacity to adequately oxidise 1,4-Dioxane, which only then can accumulate and produce cytotoxicity via a metabolic pathway in tissues with a propensity for enzyme induction (eg the liver). Enzyme induction after metabolic overloading is conceived as a threshold phenomenon and tumours arise from enforced cell proliferation rates in susceptible organs. Since this does not occur in humans in occupational settings, it cannot occur in consumers. (Kociba R et al, Toxicol Appl Pharmacol, 30:275, 1974); (Stickney J et al, Regul Toxicol Pharmacol, 38(2), 2003); (Agency for Toxic Substances and Disease Registry, Toxicological Profile for 1,4-Dioxane, ATSDR, 2007).

The media often give the wrong impression when potential cancer-causing agents are reported, which is extrapolated to produce cancer in the general public. Determining whether a chemical is a human carcinogen requires evidence from both valid and unbiased epidemiological studies ‘and’ animal bioassays. While short-term tests are helpful in decision-making, they are not as predictive as once believed. (Furst A, Intl J Toxicol, 9(1), 1990) Updated models based on more data and stronger science, provide a better understanding of 1,4-dioxane in mice, rats, and humans and a more scientifically sound basis for extrapolating data to human equivalent doses. A comparison of cancer risk estimates suggests significant overestimation of the potential cancer risk from 1,4-dioxane and critical review of the scientific literature indicates that a formal re-evaluation of the carcinogenic potency of 1,4-dioxane is warranted. (Stickney J et al, Regul Toxicol Pharmacol, 38(2), 2003); (Sweeney L et al, Toxicol Sci, 101(1), 2008)

Water is the most likely media to contain significant quantities of 1,4-Dioxane (Hartung R, Health and environmental effects assessment for 1,4-dioxane, Gelman Sciences, Ann Arbor, Mich, 1989). 1,4-Dioxane biodegrades slowly in and persists in both water and in soils, where it adsorbs weakly, but will move quickly into groundwater, where higher concentrations exist than in ambient air. Exposure to 1,4-dioxane in tap water through inhalation during showering can result in even higher exposures than from ingestion of drinking water. Because 1,4-Dioxane is miscible in water, it is not bio-concentrated in plants, aquatic organisms, or animals, although bio-accumulation may occur in plants by transpiration. (1,4-Dioxane, ATSDR, 2007) This raises the logical question of 1,4-Dioxane levels in foodstuffs, where it interestingly occurs not only as an industrial contaminant via soil, air and water, but also as a natural organic constituent.

As is often the case, in spite of no systematic scientific effort to determine the extent of its natural occurrence, 1,4 Dioxane has been reported to be present as a natural constituent in several foods, including ripe tomatoes, peppers, coffee and condiment herbs and spices, as well as in seafood, cooked meat, fried chicken and deep fry oil (within the range of 2ppm – 15ppm 1,4-Dioxane common in SLES), indicative of the likelihood of a wide range of natural occurrence, of particular interest in plants and food cooking and processing methods, largely unknown sources of exposure at present. The 1,4-Dioxane in tomatoes, especially vine-ripened tomatoes, extends also to their juices, purees, and pastes. (Chung T et al, Agric Biol Chem 47: 343, 1983); (Netherlands Org Appl Sci Res & Natl Inst Public Health Environ, ‘Risk Assessment: 1,4-Dioxane’, Ministry of Public Health, The Netherlands, 1999); (Nishimura T et al, J Health Sci, 50(1), 2004); (Agency for Toxic Substances and Disease Registry, Toxicological Profile for 1,4-Dioxane, ATSDR, 2007)

1,4-Dioxane, whether synthesised naturally by plants, fungi or animals (incl humans) or artificially, is identically biodegraded as a source of carbon by soil micro-organisms in a pathway leading to ethylene glycol and various acids (Bernhardt D, Diekmann H, Appl Microbiol Biotechnol, 36(1), 1991); (Parales R et al, Appl Environ Microbiol, 60(12), 1994); (Nakamiya K et al, Appl Environ Microbiol, 71(3), 2005) or failing this, is directly taken up as Dioxane by plants (Kelly S et al, Water Res, 25(16), 2001), so even in organic soils and plant materials (yet not crude oil/petroleum) we have these identical toxicants cycling naturally. 1,4-Dioxane concentration is higher in leaves and lower in roots, with the stem in between, unless this is of larger volume, in which case it concentrates the bulk of Dioxane. About 30% of the available Dioxane is removed from soil by plants via the roots over a week and accumulates mainly in the leaves, from which it is slowly lost to the air via transpiration. (Ying O, J Hydrol, 266(1-2), 2002)

We spend fortunes minimising carcinogenic agents created by industry, such as ammonia, formaldehyde and 1,4-Dioxane, yet these chemicals are created within our own bodies, without any help from outside forces such as polluting industry, but rather as normal by-products of both human physiological and symbiotic metabolism. (Orient J, Ch 12 in: Standard Handbook of Environmental Science, Health, and Technology, J Lehr (Ed), McGraw-Hill, NY, 2000) 1,4-Dioxane has been measured in expired air from healthy humans and attributed to normal human metabolic processes, and in some cases concentrations have been significantly higher than in urban ambient air samples from industrial cities in the USA (Conkle J et al, Arch Environ Health, 30(6), 1975); (Krotosznski B et al, J Anal Toxicol, 3:225, 1979); (Agency for Toxic Substances and Disease Registry, Toxicological Profile for 1,4-Dioxane, ATSDR, 2007).

Professor James Trefil (University of Virginia), a physicist and science textbook/communications author/editor (eg The Laws of Nature, 2002; The Nature of Science, 2003; Encyclopedia of Science and Technology, (as editor) 2004; Why Science?, 2007) has pertinently pointed out that regulatory authorities restrict these very same chemicals as petrochemical pollutants at less than one-ten thousandth of the levels that these occur naturally in our blood and intestinal gasses, and that if our metabolism were to be equally as tightly regulated, we would in fact be out of regulatory compliance by a factor of approximately 10,000 (James Trefil, Human Nature: a blueprint for managing the earth – by people – for people, Times Books, NY, 2004).

An example of nonlinear pharmacokinetics that influences toxicity, including carcinogenesis, is 1,4-dioxane. Studies have shown that in rats treated for 2-years with drinking water containing dioxane, only in doses exceeding those necessary to cause severe hepatic and renal pathology, was 1,4-Dioxane carcinogenic. Only in the high dose group (1000ppm) over 2-years, was there increased tumour incidence. (Kociba R et al, Toxicol Appl Pharmacol, 30:275, 1974) In the absence of continuous tissue damage, no tumours result. Exposure to SLES with 1,4-Dioxane does not pose a non-cancer or cancer risk, even to children. (Voluntary Children’s Chem Eval Program, Pilot Submission: 1,4-Dioxane, VCCEP, Sapphire Group, 2007)

A rare study of the pharmacokinetics and metabolism of dioxane in ‘human volunteers’ following exposure to 1,4-Dioxane vapour, revealed that repeated exposures to 50ppm for 8-hours daily, would never accumulate above concentrations attained after a single 8-h exposure, as long as the concentration of dioxane was 50ppm or less. It was concluded that even repeated occupational exposure of humans at the threshold limit value of 50ppm would not cause adverse effects. (Braun W, Waechter J, J Anim Sci, 56:235, 1983) This exposure level is impossible to achieve with any ethoxylated cleanser, even an improbable non-purified 300ppm concentration, due to insurmountable headspace air dilution and volatisation-limiting respiratory absorption safety factors inherent in even intensive usage patterns. In reality, no consumer will be directly exposed to even 1ppm respiratory dioxane from ethoxylated cleansers, and then only for the total duration of all daily exposures whilst washing hands, bathing and/or showering.

In a recent 13-week oral toxicity study in rats and mice by researchers at the Japan Bioassay Research Center of the Japan Industrial Safety and Health Association, 1,4-dioxane was administered in drinking water and effects noted primarily between 10,000ppm and 25,000ppm. A no-observed-adverse-effect-level (NOAEL) was set at between 4000ppm in mice and 1,600ppm in rats between the species and sexes and determined at 640 ppm for both. (Kano H, J Toxicol Sci, 33(2), 2008) Again, in reality, no consumer using any ethoxylated cleanser is going to accidentally ingest even 1ppb of 1,4-Dioxane during routine product use.

To place parts per million (ppm) and parts per billion (ppb) concentrations into realistic relative perspective, consider that 1ppm is the equivalent of 1-second in 11½ -days and 1ppb, 1-second in 32 years. A worst case scenario from use of a full strength ethoxylated SLES cleanser with little of its 1,4-Dioxane impurities effectively removed, would contain a likely maximum of some 180ppm, the concentration equivalent of losing normal sleep for 1-hour in 2-years. Even the heaviest use of such impure SLES, would not result in effective skin or mucosal (alimentary or lung) permeation and absorption of Dioxane in excess of a mere insignificant 1ppm, the concentration equivalent of losing normal sleep for only 20-seconds in 2-years - generally less 1,4-Dioxane than from the daily consumption of a tomato puree- or paste- based meal. A more realistic average consumer’s 1,4-Dioxane exposure concentration would be 1ppb, equivalent to losing normal sleep for a mere 1-second in 94 years – about a single daily serving of tomato.

Given the high-dose direct continuous exposures needed to induce toxicity in animal studies compared with the low and temporary exposures of consumers, it is simply impossible for there to be at any risk whatsoever from trace impurities of 1,4-Dioxane from an ethoxylated rinse-off cleanser such as SLES, or even all possible combined exposures to 1,4-Dioxane, without daily drinking a bottle of shampoo or cleanser or injecting a functional application amount of it. Anyone claiming otherwise is a political strategist with a hidden agenda (blind organic lobbyist), a mischievous troublemaker creating a false scare for commercial expediency, an ignoramus or a silly scammed sucker. I state this with conviction as a long-time organic food gardener with pioneering botanical pesticide expertise, 30-years as an independent natural health researcher and with a 15-year background in formulating pioneering natural health/personal care products.

The Calfornia Attorney General’s Office enforces Proposition 65. Any individual purporting to be acting in the public interest may trigger Proposition 65 action, including district attorneys, consumer advocacy groups, private citizens and law firms. Penalties per violation can be as high as $2,500/day and so run into millions of Dollars without even a defendant’s awareness. In early 2008, the Organic Consumers Association, a vested interest lobby group conspiring against competition from petrochemical inputs, announced via press releases, the detection in ‘organic’ personal care products containing SLES, of trace residues of 1,4-Dioxane, a fact known for 30 years. A situation in which a self-serving OEHHA, rather than the state or national treasury keeps the financial penalties bar for 25%, which accrues to the plaintif as a ‘bounty hunter’, but exempts the legislating and adjudicating state itself from prosecution for violations, would not be tolerated by a credible court anywhere else in the world in modern times, clearly illustrating the populist punitive cowboy politics involved, albeit well-intentioned by the citizenry.

Significantly, albeit open to much legal interpretation and considerable scientific controversy, “all businesses are also exempt from the warning requirement if the exposures they cause are so low as to create no significant risk of cancer”. For a carcinogen, the "no significant risk level” is defined as exposure that would result in not more than one excess case of cancer in 100,000 individuals exposed thereby over a 70-year lifetime. The OEHHA develops guidance levels for determining whether a cancer warning is necessary. Most oddly, businesses with less than 10 employees and even more contentious, ‘government agencies’ are ‘exempt’. The “safe harbour” levels tend to err massively on the side of caution, but do not preclude the use of alternative levels if demonstrable as scientifically valid, though a stubborn, illiberal, inflexible and narrow mind-set prevails regarding challenges from modern toxicological science that might threaten their traditional authorative comfort zone, eg their injunction that “the absence of a carcinogenic threshold dose shall be assumed”, where a threshold clearly applies.

Other scientifically and morally indefensible ‘exemptions’ to Proposition 65 are “naturally occurring chemicals in foods” and more recently, “where chemicals are produced by cooking necessary to render the food palatable or avoid microbiological contamination”, as a result of political lobbying to avoid a standoff that might otherwise have reformed many harmful practices, yet this exemption was ushered in to bypass a sticky problem for both sides, in spite of relatively higher cancer burdens from listed chemicals from these sources than many condemned intentional and incidental man-made chemicals. These blatant double standards place citizens at unreasonable risk from ‘natural chemicals’ of a far more prolific and insidious nature. A listed chemical was previously considered “naturally occurring only to the extent that the chemical did not result from any ‘known’ human activity” and “only to the extent that it was not avoidable by ‘good’ agricultural / manufacturing practices”, but the cooking exemption places even this qualification in jeopardy. The phrase “naturally occurring” has been interpreted by radical plaintiffs to mean that a chemical cannot be present in food from ‘any’ human activity.

In 1988, OEHHA’s predecessor, the Health and Welfare Agency, had already promulgated an exception, which provided that human consumption of a food shall not constitute an ‘exposure’ to a listed chemical in food to the extent that the person responsible for the exposure can show that the chemical is ‘naturally occurring’ in the food. A chemical was thus declared to be ‘naturally occurring’ if it is “a natural constituent of a food or if it is present in a food, solely as the result of absorption or accumulation of the chemical, which is ‘naturally present’ in the ‘environment’ in which the food is raised, or ‘grown’, or obtained”. Consider this along with the qualification: “only to the extent that it is not avoidable by ‘good’ agricultural / manufacturing practices” and the food exemptions reappear as legitimate legal candidates for warning labels. Clearly, an inconsistency was known to exist and a solution thought to have been found via said exemptions, failing which all grocers and most other vendors would have been required to post a warning label on most, if not all, food products. Such warnings would thereby have been diluted to the point of meaninglessness and, perhaps correctly, might have defeated the initiative. However, this situation is already exists with many listed anthropogenic (man-made or caused) carcinogens and toxins, hence another stop-gap exemption on carcinogens produced by cooking and heat processing, to keep the initiative manageable. A challenge is imminent.

What now of ‘known’ ‘organic farming’ practices that inevitably increase the natural production of endogenous defensive plant toxins thousand-fold in organic produce? A California Court has already ruled that the regulation’s drafters intended only exempting chemicals in food that are the result of “uncontrollable human activity”. Exemptions, especially in light of the ‘controllable’ organic paradox, go to the heart of the purpose of the act and needs to be tested in court. Recall that tomatoes, especially vine-ripened tomatoes, and all their concentrated juices, purees and pastes contain increasing concentrations of 1,4-Dioxane. Significantly and perhaps fortuitously, California is not only the tomato growing, but is also the organic farming capital of America. Tomatine, another ‘natural’ chemical toxin in tomato is present at 36mg/100g tomato (360ppm) in a regular tomato, a concentration that is much closer to the acutely toxic level than are man-made pesticide residues (Jadhav S et al, CRC Crit Rev Toxicol 9:21, 1981). Neither tomatine, nor its aglycone, tomatidine, an anti-fungal steroid-like molecule, has been tested in rodent cancer bio-assays (Ames B et al, Chapter 3 in Hikoya Hayatsu and Veikko Sorsa, ‘Mutagens in Food: Detection and Prevention’, CRC Press, 1990).

There is a tendency for non-scientists to think of chemicals as being only synthetic and toxic, as if natural chemicals were not also toxic at some dose. One consequence of disproportionate concern over tiny traces of synthetic manmade pesticides is that plant breeders are developing plants for the ‘organic’ food market that are highly pest resistant, ie are ‘high in natural toxins’. See my treatise on this counter-intuitive paradox here. Moreover, a regulatory agency, in the absence of express authority in the statute itself, cannot by regulation, adopt exemptions to the statute. Where a statute does empower an administrative agency to adopt regulations, these must be consistent with the statute, and must effectuate its purpose. Administrative regulations that alter or amend the statute or enlarge or impair its scope are void and courts not only may, but it is their obligation to strike down such regulations. I foresee a big showdown over the arbitrary exemptions and glaring exclusions from the listed chemicals and would have full confidence in defeating a challenge of a warning violation, were I subject to Californian statutes.

The OEHHA has established a “No Significant Risk Level” (NSRL) for 1,4-Dioxane of 30µg/day over a life-time based on data from the late 1970’s using a standard, linearised, multistage procedure, but more recent data and toxicological analysis suggest that OEHHA’s NSRL is a substantial under-estimate and much higher doses are also likely to represent no significant risk of cancer (Stickney J et al, Regul Toxicol Pharmacol, 38(2), 2003); (most of the other Dioxane references cited above). This OEHHA NSRL is ultra-conservative, archaic, scientifically tenuous and many-fold overly stringent. Based on modern procedures and data, ethoxylated SLES-based cleansers result in much smaller doses/effective permeation/absorption levels and risk than estimated for said purpose, additional toxicological arguments in defense of such products are not presented, other than to point out that no self-respecting other international or national regulator anywhere else in the world considers such traces of 1,4-Dioxane to be a real threat.

Claims of a cancer risk from trace residues of 1,4-Dioxane in ethoxylated cleansers are simply ridiculous; since this would require drinking or exclusively inhaling entire SLES products on an ongoing basis, for which insane deviation from intended use, no formulator or manufacturer could conceivably be held responsible. International regulators have dismissed the importance of 1,4-Dioxane as a health issue, based on the low concentrations/dilutions involved, the evaporation thereof and the miniscule fraction that penetrates the skin and is absorbed. On a basis of the considerable current scientific data against all, including reasonable worst-case usage patterns, it can only be concluded that the presence of 1,4-Dioxane is of no toxicological significance in rinse-off / dry-off ethoxylated cleansers, or in terms of the currently contentious, State of California’s Proposition 65, a “no significant risk level” (NSRL) must apply.

Dr Joe Schwarcz, a chemistry professor at McGill University in Montreal, Canada and director of McGill’s Office for Science and Society, has pointed out that though some personal care product ingredients may be contaminated by 1,4-dioxane, a known carcinogen, the practical relevance of this is highly suspect. Not only does he invoke the pivotal credo of toxicology, attributed to Paracelsus in the sixteenth century, that “only the dose makes the poison” (a point apparently still not grasped by many ignorami several centuries later), but further points out that not only might tiny doses of toxins not be dangerous: they may even be good for us! This revolutionary concept, known as "hormesis", contends that traces of toxins can reliably stimulate beneficial protective mechanisms, whilst posing no risk of real harm whatsoever.

To skip to the short version, click here.

Schwarcz relates how Edward Calabrese, now a professor of toxicology at the University of Massachusetts and recognised as the world authority on exposure to trace chemicals, originally got interested this phenomenon, when as an undergraduate he became involved in a project to investigate the amount of herbicide needed to stunt the growth of plants. To his surprise, the plants actually grew more vigorously after being sprayed with the chemical, which it turned out, was improperly prepared and was far more diluted than intended. Thousands of publications now document dramatically different, including totally opposite, even practical effects from very low concentrations of even the most potent toxins (are they still?) compared with their quantified toxicity at higher doses. (Schwarcz J, Toxins and Your Good Health, Arts Opin 3(4), 2004)

The scientific axiom “Sola dosis facit venemum” (the dose makes the poison), whilst a profound truism, does not address the shape of the curve linking both ends of the exposure scale. Paracelsus did, however, also note that toxic substances could be beneficial in small quantities and progressive modern toxicologists revived this concept nearly 30-years ago (Stebbing A, ‘Hormesis - the stimulation of growth by low levels of inhibitors’, Sci Total Environ 22(13), 1982). It was Hugo Schulz’s linking of hormesis to the controversial practice of homeopathy that brought him fame and infamy, but also, due to ideological perspectives, prevented the fledgling hormetic dose–response theory from receiving an open hearing within the confines of medical science and its later disciples, toxicology and risk assessment. Surprisingly, despite his later controversial standing in the biomedical sciences, Hugo Schulz was nominated half a century later in 1931 for the Nobel Prize based on his original 1887/1888 medical hormesis publications.

Harmful agents may induce toxicity, but all organisms respond to damage signals with a coordinated series of temporally mediated repair processes. Hormesis is an overcompensation following an initial disruption in homeostasis, a rebound effect representing a reparative process that slightly overshoots the original homeostatic set point, resulting in a modest low-dose stimulatory response, generally allocated highly efficiently during the reparative process. Hormesis epitomises whichever benefits are gained from resources allocated for repair activities in excess of what is needed. This advantage can pre-adapt the organism against damage from subsequent and greater exposure within a limited time frame and assure that repair is accomplished adequately and timeously. Possible natural mechanisms are multiple, eg enzymes that repair damaged DNA, immune response stimulation, and apoptotic elimination of damaged cells, which, if not initiated early and adequately, can lead to development of cancer.

It is generally accepted that there can be numerous changes to organisms following exposure to a chemical, be it beneficial, adaptive, early manifestations on a continuum to toxicity, overt toxicity, or several of these in combination. This applies to man-made and natural chemicals. Under hormetic conditions, low doses can prompt temporary dissociation from homeostatic equilibrium and a degree of over-compensation. Potentially toxic phyto- and anthropogenic- chemicals can at hormetic doses, protect plants and animals, including humans, from not only their own kind, but also each other. Higher doses can push organisms beyond the limits of kinetic or dynamic recovery, the classical object of toxicological research and regulatory activity. As knowledge and power are interrelated in precautionary culture, hormetic responses are by default regarded as irrelevant, even though its consideration would improve public health policy.

Constraint of hormetic responses at 30 - 60% greater than controls indicates a highly conserved strategy. Biological systems do not even have to be damaged for hormetic benefit, if directly stimulated (Calabrese E, Baldwin L, Hum Exp Toxicol 21:91, 2002). One can safely be stressed daily by a vast array of chemical or other stimuli and thereby induce hormetic mechanisms that prevent disease processes and enhance health outcomes. It appears that to optimise health, biological systems need to be routinely stressed, in conformance with the hormetic dose response parameters. (Mattson M, Cheng A, Trends Neurosci, 29(11), 2006) It is common wisdom that an infant benefits from earlier rather than later exposure to the world at large and that without such challenges is unlikely to cope as well with sudden delayed exposure. This is the hormetic principle in action and extends into adulthood until somehow severely constrained.

The toxicological database of hormetic dose response studies contain thousands of hormetic dose–response relationships across thousands of agents over a broad spectrum of chemical classes, physical agents and biological models, including plants, viruses, bacteria, fungi, insects, fish, birds, rodents, and primates/humans. The modern father of hormesis, Edward Calabrese (after Rudolph Verchow, Hugo Schulz and Anthony Stebbing) correctly ridicules the old paradigm and its adherents and has submitted and successfully published, an ‘Obituary’ for the concept of the Threshold Dose–Response Model, which has so long dominated toxicology and outlived its utility to (poorly) predict low-dose responses, thus: “After a long illness, the Threshold Dose–Response Model (TM) died following a recent publication in Toxicological Sciences, which determined that TM lacked ability to predict responses in the low-dose zone”. (Calabrese E, “Threshold Dose--Response Model--RIP: 1911 to 2006”, Bioessays, 29(7), 2007)

Hypothesising cancer risk at even low dose ambient exposures is questionable, especially in light of much experimental evidence indicating protective effects of low doses (Ricci P, MacDonald T, Human Exp Toxicol, 26(11), 2007). Regulators should rethink their 'when in doubt, keep it out' linear toxicological approach and take hormesis seriously, which might well be the 'brake' for the looming 'collision' with scientific reality (Hanekamp J, Bast A, Hum Exp Toxicol, 26(11), 2007). The hormetic dose–response is far more common than the threshold and linear no threshold dose–response models used by government regulatory agencies in the establishment of exposure standards. Understanding and acceptance of hormesis has the potential to profoundly affect the practice of risk assessment, especially with carcinogens. (Calabrese E, Crit Rev Toxicol, 38(5), 2008); (Calabrese E, Ageing Res Rev, 7(1), 2008)

The dominant regulatory culture of risk-aversion engenders a policy culture that is most easily served with the old linear approach to toxicity. The enlightened hormetic toxicology scientific community (understanding that the most fundamental shape of the dose-response curve is neither threshold nor linear, but J/U-shaped) from an impressive and broad range of disciplines, are not only already actively integrating the discipline, but are also increasingly educating fellow scientists and challenging and the resisters of change by intellectually prescribing to regulators (obstinate in their government awarded authority) as to how they ought to timeously adapt to the evolution of science in society’s interest, a principle so fundamental to it being called ‘science’ in the first place. (Calabrese E et al (59 co-authors), Toxicol Appl Pharmacol, 222(1), 2008)

The key factor in the hormesis concept is not the chemical, but the organism, the response being the organism’s overcompensation to a disruption in homeostasis. Therefore, any agent can induce a hormetic response. This does not infer that all chemicals will be hormetic for all endpoints, but rather that biological systems respond in a hormetic manner to signals that indicate stress, toxicity, or disruptions in homeostasis. It is now known that low doses of antiviral, antibacterial, and anti-tumour drugs can may be hormetic for the disease-causing organisms and enhance the growth of potentially harmful viruses, bacteria and malignant cells, possibly harming the patient. Fortunately, in assessments of immune responses to date, approximately 80% of hormetic responses assessed for clinical implications have been rated as being beneficial to humans. (Calabrese E, Critical Review, ‘Hormesis: “Why it is Important to Toxicology and Toxicologists”, Environ Toxicol Chem, 27(7), 2008)

The US EPA and copy-cat regulatory agencies use a model for carcinogens in risk assessment that cannot be validated for a low level of estimated risks. Conversely, hormetic low dose responses can be readily tested, assessed for accuracy and validated, but is more difficult. Some tumour promoters and/or metabolites acting via inhibition of cell-to-cell communication have been reported to enhance opposite protective activity at lower doses, showing the biphasic dose–response features of hormesis (Zeilmaker M, Yamasaki H, Cancer Res, 46:6180, 1986). A common example of major practical importance in this regard, is that of hydrogen peroxide (Mikalsen S, Sanner T, Carcinogenesis 15:381, 1994). It is confirmed from the dose-response relationships produced by the 24,000-animal US-Government (ED01) study, that genotoxic carcinogens can also induce hormetic effects (Bruce R et al, Fundam Appl Toxicol, 1:26, 1981) – though the word ‘hormetic’ was not used at the time. Xenoestrogens also display hormetic dose responses. (Calabrese E, Critical Review, Environ Toxicol Chem, 27(7), 2008)

It is appropriate that risk characterisation of non-genotoxic (epigenetic) carcinogens, eg 1,4-Dioxane be treated differently to genotoxic carcinogens. At toxic doses, Dioxane increases lipid peroxidation, a potential mechanism of cell damage and precursor of carcinogenicity. However, lower dose 1,4-Dioxane metabolites paradoxically act as antioxidants (Pawar S, Mungikar A, Bull Environ Contam Toxicol, 15(6), 1976). Epigenetic carcinogens require a threshold dose to elicit harmful effects, so a Margin of Safety approach is generally recommended. Because dermal exposure to 1,4-Dioxane is unlikely to contribute significantly to body burden, a margin of safety is calculated as an ‘inhalation’ NOAEL of 111ppm. In view of the relatively small amounts in ethoxylated personal care products, health risks to industry and end-users are considered low. (NICNAS, Priority Existing Chemical Assessment Reports - 1,4-Dioxane, Dept Health & Aging, Australia, 1998/2007) Epigenetic carcinogens are known to act in a hormetic fashion in rigorously designed rodent carcinogen bioassays (Fukushima S et al, Carcinogenesis, 26:1835, 2005); (Kinoshita A et al, J Toxicol Pathol, 19:111, 2006).

1,4-Dioxane is known to exhibit immune-system stimulating hormetic dose-responses (Kitchen K, Brown J, “Dose-response relationship for… 49 rodent carcinogens” Toxicol, 88(1-3), 1994); (Calabrese E, Biological Effects of Low Level Exposures, 3(3), 1995); (Calabrese E, Baldwin L, Regul Toxicol Pharmacol, 28(3), 1998); (Calabrese E, Crit Rev Toxicol, 35(2&3), 2005); (Ricci P, MacDonald T, Hum Exp Toxicol, 26(11), 2007); (Pers Comm, Calabrese E, 29-7-2008) and plant growth stimulation (Morre D, Hum Exp Toxicol 17(5), 1998). While not suggesting that 1,4-Dioxane be deliberately used in personal care products for this purpose, I am of the informed opinion that even in any conceivable worst-case scenarios of consumer exposure via ethoxylated cleansers, the insignificant amounts of any trace contaminant 1,4-Dioxane actually impacting cellularly and/or physiologically on even the most vulnerable individuals, eg infants, would not only represent no possible risk at all, but rather, would serve to act hormetically to exert a modest beneficial immune stimulating effect, if indeed anything at all.

Aging is primarily the result of a failure of maintenance and repair mechanisms. Stimulation of these pathways via a variety of the hormetic stressors is reported. Hormesis is a promising approach for modulating aging and age-related diseases via modest stimulation of various cellular and biochemical functional characteristics of human skin fibroblasts. (Rattan S, J Geroltol A Biol Sci Med Sci, 59(7), 2004). Beneficial effects include the maintenance of a favourable stress protein profile, reduction in the accumulation of oxidatively and glycoxidatively damaged proteins, stimulation of the proteasomal activities for the degradation of abnormal proteins, improved cellular resistance to other stresses, and enhanced levels of cellular antioxidant ability. (Rattan S et al, Acta Biochem Pol, 51(2), 2004) The progression of cellular ageing can be slowed without upsetting the regulatory mechanisms of the cell cycle by using the body’s intrinsic capacity for self-maintenance and repair, where via such protective low dose toxin hormetic effects, the quality of life of cells in terms of their structural and functional integrity can be improved without pushing them cells into a potentially carcinogenic hyper-proliferative mode. (Rattan S, EMBO Report 6 (Special Issue), Europ Molec Biol Org, 2005)

Progressive accumulation of molecular damage to human skin fibroblasts and keratinocytes, a hallmark of cellular aging, is thus amenable to targeted biological hormetic interventions and preventions (Rattan S, “Principles of Ageing and the Practice of Anti-ageing Therapies”, Asian J Exp Sci, 20(1), 2006). Application of hormesis as an anti-aging approach is gaining wide recognition and acceptance. Various chemical stressors, including oxidants, both synthetic and natural (such as Hydrogen Peroxide and 1,4-Dioxane) are reported to delay aging and prolong life in various systems, under which circumstances they are classified as hormetins. (Rattan S, Ali R, Ann NY Acad Sci, 1100:424, 2007); (Rattan S, Ann NY Acad Sci, 1114:1, 2007) Almost all antioxidants show hormetic dose response and become pro-oxidants above certain doses. Furthermore, in some cases such as alpha lipoic acid and coenzyme Q10, it is their pro-oxidant activity in producing hydrogen peroxide, which induces defensive responses, which are the basis of their ultimately beneficial effects (Linnane A et al, Biogerontol, 8:445, 2007)

Hormesis appears to be a common phenomenon in dermatology. Skin is an excellent hormesis candidate due to its repertoire of inflammatory and immuno-modulating cytokines, hormones and vitamins, and its unique responses to ultraviolet light, toxins, and injury. More focus should be redirected from looking only at adverse effects at high levels of exposure to characterizing the complex beneficial biological effects at low levels of exposure (Thong H, Maibach H, Cutan Ocul Toxicol, 26(4), 2007); (Thong H, Maibach H, Dose Response 6(1), 2008). Molecular mechanisms facilitating hormetic effects comprise of a cascade of stress response maintenance and repair pathways. Although the extent of immediate hormetic effects after exposure to a particular stress may only be moderate, chains of events following initial hormesis can lead to biologically amplified effects that may be much larger, synergistic and pleiotropic. The consequence of hormetic amplification is increased overall cellular and systemic defense capacity. Exposure to low doses of potentially harmful agents can have a variety of anti-aging and longevity-extending hormetic effects. (Rattan S, Am J Pharmacol Toxicol, 3(1), 2008)