Alcohol, used as a herbal extractive solvent (tincture) or a preservative in skin-care products is not strictly natural. It is artificial, indeed synthetic, even if the raw materials are potatoes or grains and sugars and yeasts, since it is not harvested from within nature, but rather is synthesised via a man-made industrial laboratory process that is optimised under controlled conditions that do not spontaneously exist in nature. At best, it may be nature-identical. Dr Hauschka hypocritically malign the safer nature-identical parabens, yet acknowledge having 7-12% alcohol in their skin-care products, a concentration simply never occurring in nature and significantly toxic to skin cells.

Alcohol is bacteriostatic and fungistatic at 10% and reliably bactericidal and fungicidal at 30 and 35% respectively (Victor Lorian [Editor], Antibiotics in Laboratory Medicine, Lippincott Williams & Wilkins, Philadelphia, USA, 2005). Even at such high concentrations, alcohol lacks the residual antimicrobial activity that is prerequisite to ensuring consumer protection from microbial decomposition of their higher ‘organic’ content and toxic byproducts thereof. Due to its high volatility and eventual metabolism in the skin (to more toxic compounds), once alcohol-preserved products are applied to the body, efficacy against microbes is relatively short-lived, yet dermal cytotoxicity persists. Such products dry the skin and must be formulated with inappropriately heavy occlusive emollients such as castor oil and/or lanolin (more suited to ointments) to retard evaporation and mask the presence of dying and dead skin.

Let us evaluate the skin cytotoxic potential of alcohol (whatever its source, but restricted to ethyl alcohol - hereafter referred to as alcohol, as used by e.g. Dr Hauschka and other so-called natural / organic manufacturers). When alcohol was tested for toxicity in dose response measurements on histocultured skin exposed to various concentrations of alcohol for five minutes and the cell types (epidermal, dermal, and follicle cells) within the intact skin were observed for toxicity, it was determined that before alcohol exposure, most of the cells were viable, but subsequent exposure to alcohol caused more epidermal and dermal cells to be nonviable with increasing concentration of alcohol, which killed cells independent of type (Li L et al, Proc Natl Acad Sci USA, 88:1908, 1991).

Alcohol is a significant penetration-enhancer through an otherwise normal skin barrier, primarily due to the extraction of intercellular lipids from the stratum corneum. Compromised skin barrier function increases susceptibility for damage of the skin and permeability by other chemicals. (Smith E and Maibach H, Percutaneous Penetration Enhancers, CRC Press, 1995); (de Haan P et al, In: Pieter van der Valk & Howard Maibach (Eds.), The Irritant Contact Dermatitis Syndrome, Informa Health Care, 1996) Substances applied to the skin can diffuse across the protein/lipid barrier into keratinocytes below. Facial skin is even more permeable, which is of consequence because many alcohol-containing cosmetics, creams, lotions and gels are commonly regularly applied to the face. (Neuman M et al, Alcohol, 26(3), 2002) Ethanol can be a skin allergen in immediate and delayed hypersensitivity by external or internal exposure and can produce subjective irritation, irritant contact dermatitis and non-immunologic contact urticaria (Ophaswongse S, Maibach H, Contact Dermatitis, 30:1, 1994)

In recent experiments, erstwhile collaborators of mine (Dept Clinical Pharmacology, Dermatology & Medicine, Sunnybrook and Women’s Health Sciences Centre, Canada) exposed human skin cells to 40 mM of alcohol (average blood alcohol concentration of an adult after 3 glasses of wine - much less than the quantity deliberately formulated into many cosmetics, in particular so-called ‘organic’ products and hence an increasingly common occurrence). Alcohol-exposed cells released pro-inflammatory cytokine tumour necrosis factor-alpha, which initiated disruption of mitochondrial membrane potential and cell death. Electron microscopy revealed that alcohol exposed human skin cells, even at very low concentrations caused organelle damage, condensed chromatin, decreased cell size and increased apoptotic bodies (cellular suicide). (Neuman M et al, Alcohol, 26(3), 2002)

Psoriasis and eczema are associated with excessive alcohol exposure (Higgins E, du Vivier A, Alcohol and the Skin, Alcohol Alcohol, 27(6), 1992). Canadian collaborators of mine investigated whether alcohol plays a role in the pathogenesis of psoriasis by up-regulating humoral pro-inflammatory cytokines and concluded that in normal human skin cells, toxicity and psoriasis-causing inflammatory responses are enhanced by a concentration as low as 40 mM alcohol (Shear N, Skin Pharmacol Skin Physiol, 12(1-2), 1999). Furthermore, paradoxically, alcohol concentrations below levels that induce cytotoxicity (0.1–0.5%), may be immuno-suppressive by inhibiting the inflammatory response and thereby impairing associated cellular immune responses to infectious challenge, thereby increasing the risk of infection for several hours (Saeed L et al, J Immunol, 173(10), 2004).

There are several mechanisms by which alcohol is cytotoxic. Some involve direct cytotoxic action of alcohol itself, without being metabolised, primarily via the generation of oxygen radical intermediates and free radicals (Mufti S et al, Alcohol Alcohol, 28(6), 1993); (Kosaka T et al, Acta Medica Okayama, 50(3), 1996). The most toxic action of alcohol results from its even more toxic metabolite, acetaldehyde (approximately 30 times more toxic), which is produced from alcohol by several enzymes in human skin (Milton K, Integrat Comparat Biol, 44(4), 2004). Somewhat reduced toxicity might result from further breakdown of acetaldehyde (which is related to formaldehyde) to acidic toxic oxidation transition products, including carboxylic acids. If acetaldehyde is not eventually efficiently converted into acetic acid (the acid in vinegar), severe toxicity can result. (Cheung C et al, Toxicol, 184(2-3), 2003)

Researchers have detected important classes of enzymes involved in the biotransformation of both alcohols and aldehydes in human skin (Cheung C et al, Biochem Biophysic Res Comm, 261(1), 1999), that present skin sensitisation hazards with potency relative to the extent of metabolism in the skin. Alcohol dehydrogenase (ADH) enzymes catalyse the interconversion of alcohols and aldehydes and convert aldehydes to acids. Aldehyde dehydrogenase (ALDH) enzymes/catalyse the oxidation of aldehydes to carboxylic acids. The enzymes are present in human skin, predominantly in the epidermis and appendages (sebaceous glands and hair follicles). These enzymes in human skin have toxicological significance i.r.o. the metabolism of xenobiotic (topically applied solvent tincture and preservative) ethyl alcohol and the resultant aldehydes. (Cheung C et al, Toxicol, 184(2-3), 2003)

The enzymatic breakdown of alcohol results in the generation of the toxic reactive molecule, acetaldehyde and as a byproduct, highly reactive oxygen radicals that interact with lipid molecules in cell membranes and via lipid peroxidation, generate additional reactive molecules, especially malondialdehyde and 4–hydroxy–2–nonenal. These interact with proteins, lipids and DNA to form adducts (hybrids) that impede the normal functions of proteins and induce harmful immune responses. These effects can lead to cellular dysfunction, cell damage and cell death. (Tuma D et al, Dangerous By-products of Alcohol Breakdown – Focus on Adducts, NIAAA, NIH-USA, Oct 2004)

Collagen, the major protein in connective tissue (including the skin and loss of which results directly in wrinkles), is one protein preferentially damaged by alcohol aldehydes. Cross-linking is a process by which “molecular bridges” are formed between “reactive sites” on different molecules. Acetaldehyde induced cross-links tie up affected molecules and interfere with their normal vital functions, which may even be completely blocked. This process of cross-linking is largely responsible for the visible age-related changes in human skin that make it inflexible, sagging, wrinkled and dry. (Fowkes S, Smart Drug News, 5(5), 1996); (Tuma D et al, NIAAA, 2004)

Alcohol exposure is highly conducive to the generation of oxygen free radicals and the subsequent attack of fragile polyunsaturated lipids, thereby producing cytotoxic lipid peroxidation products. Aberrations in phospholipid and fatty acid metabolism, changes in cellular redox state, disruptions of the energy state, and increased production of reactive oxygen metabolites are implicated in cellular damage resulting from both acute (occasional) and chronic (ongoing) exposure to alcohol. Non-oxidative metabolism of alcohol is furthermore an additional toxic mechanism by which alcohol affects membrane structure and compromises cell function. (Baker R, Kramer R, Ann Rev Pharmacol Toxicol, 39(1), 1999); (Corey S et al, In Vitro Cellular & Develop Biol – Anim, 40(3), 2004)

Alcohol exposure can be directly involved in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which form an environment favourable to oxidative stress. ROS and RNS play an important role in alcohol cytotoxicity via DNA damage, lipid peroxidation and protein modification. Alcohol-induced oxidative stress is linked to the metabolism of ethanol involving both microsomal and mitochondrial systems. Alcohol exposure results in the depletion of GSH levels and decreases antioxidant activity. It elevates malondialdehyde, hydroxyethyl radical and hydroxynonenal protein adducts. These cause the modification of all biological structures and consequently result in serious malfunction of cells and tissues. (Das S, Vasudevan D, Life Sci, 81(3), 2007)

It is difficult to differentiate between the tumour-promoting and cancer-causing effects of alcohol and acetaldehyde, the biological breakdown product of alcohol. They share similar mechanisms, but the latter is 30 times more toxic.

Alcohol can generate oxygen radical intermediates and free radicals, leading to lipid peroxidation, which promotes tumours (Mufti S et al, Alcohol Alcohol, 28(6), 1993). Observations from experimental carcinogenesis and clinical studies indicate that though it cannot initiate carcinogenesis by itself, alcohol acts as a tumour promoter. Alcohol is cytotoxic and the injury induced may cause cell atrophy or cell death and sometimes, subsequent cell proliferation, culminating in some facet of neoplastic development. Studies suggest that long-term alcohol exposure favours malignant development of chemically induced lesions. Thus, alcohol has can play an active role where carcinogenesis stimulus are further developed by a dysplastic proliferative response and possibly an increase in malignancy. (Ronald Watson, Alcohol and Cancer, CRC Press, 1992); (Cederbaum A, BioFactors, 8(1-2), 1998)

Ethyl alcohol is a very potent radiomimetic agent, producing chromosome aberrations comparable to those induced by ionizing radiation. A concentration of 0.12 per cent alcohol produces a small increase over controls, and 0.25 per cent induces a substantial increase. A concentration of only 0.5 per cent alcohol was equivalent to about 20 rad/day of chronic gamma radiation, or an accumulated dose of 75 rad. To put this in perspective, the Atomic Energy Commission maximum permissible dose for radiation workers is a mere 0.1 rad per week, and for the general public, a miniscule 0.01 rad per week. (Sax K, Sax H, Proc Nat Acad Sci USA, 55(6), 1966) Serious shit! DNA reactions with alcohol occur under physiological conditions in the presence of activating agents such as free radicals and exposure to UV or visible light. (Fraenkel-Conrat H, Singer B, Proc Natl Acad Sci USA, 85:3758, 1988)

The European Chemicals Bureau has proposed the classification of alcohol as a mutagen (ECBI/74/95-Add 3) under the Dangerous Substances Directive (67/548/EEC) and the German Commission for the Investigation of Health Hazards of Chemical Compounds classified it as a Category 2 Mutagen. The genetic effects are mostly due to the metabolite acetaldehyde, produced in the liver and skin. (Phillips B, Jenkinson P, Mutagenesis, 16(2), 2001) Alcohol has been demonstrated to be carcinogenic for various organs and tissues and must be considered a multipotential carcinogenic agent (Soffritti M, et al, Annal N Y Acad Sci, 982(1), 2002).

Alcohol itself is not a carcinogen but under certain conditions is a co-carcinogen and/or tumour promoter. Alcohol exposure inhibits natural killer (NK) cell activity and reduces NK cell number. A major impact of alcohol on the immune system favouring tumour development is undisputed. (Pöschl G, Seitz H, Alcohol Alcohol, 39(3), 2004) Alcohol may also stimulate carcinogenesis by inhibiting DNA methylation (Seitz H, Stickel F, Nat Rev Cancer, 7(8), 2007). Experimental alcohol exposure results in increases in VEGF mRNA and its receptor protein levels in mammalian melanoma, with significantly increased melanoma growth (triple tumour weight) (Tan W et al, Cancer Biol Ther, 6(8), 2007).

Acetaldehyde is produced by the oxidation of ethyl alcohol in the body, including in the skin of humans. Mere micromolar concentrations of acetaldehyde, causes a wide range of cytopathic effects associated with multistep carcinogenesis. Acetaldehyde cytotoxicity causes comparatively higher genotoxicity and inhibits DNA repair more readily than other major aldehydes in tobacco smoke, automotive emissions and the manufacturing of plastics. (Grafström R et al, Carcinogenesis, 15(5), 1994) According to the International Agency for Research on Cancer there is sufficient evidence for acetaldehyde as a carcinogen in experimental animals (Acetaldehyde. Monograph: Evaluating the Carcinogenic Risk of Chemicals to Humans, Vol. 36, IARC, Lyons, France, 1995).

Acetaldehyde is genotoxic, inducing gene mutations, clastogenic effects, and sister-chromatid exchanges in mammalian cells in the absence of exogenous metabolic activation. There is indirect evidence from in vitro and in vivo studies to suggest that it can induce protein-DNA and DNA-DNA cross-links (Rieger R, Michaelis A, Biol Zent, 679: 1, 1960); (Cortes F et al, Mutat Res, 171(2-3), 1986); (de Fouw J, Acetaldehyde, Environmental Health Criteria 167, International Programme on Chemical Safety, UNEP / ILO / WHO, 1995)

Alcohol and acetaldehyde have both been implicated in carcinogenic and other cytopathologic processes. These reactions are of biological concern because they can occur in dilute aqueous solution under physiological conditions (such as alcohol preservation of skin / body care products). (Fraenkel-Conrat H, Singer B, Proc Natl Acad Sci USA, 85:3758, 1988) Acetaldehyde reacts with and causes DNA damage. Since it is reactive with the amino residue, it can also react with proteins, amino acids and RNA molecules. Acetaldehyde causes cancers in animals and tumours, if not cancer, in humans. (Matsuda T et al, Nucleic Acid Res, 26(7), 1998)

The metabolism of alcohol leads to the generation of acetaldehyde and free radicals. Acetaldehyde is carcinogenic and mutagenic, binds to DNA and proteins, results in hyper-proliferation and is predominantly responsible for alcohol-associated carcinogenesis. It causes mutations and gross chromosomal aberrations and interferes with the DNA repair machinery. Acetaldehyde also binds rapidly to cellular proteins and DNA, resulting in morphological and functional cellular impairment. Binding to DNA triggers replication errors and/or mutations. These acetaldehyde-associated effects occur at concentrations as low as 40 µmol/l, which are similar to concentrations observed in human saliva following alcohol ingestion (and topical exposure). (Pöschl G, Seitz H, Alcohol Alcohol, 39(3), 2004).

Acetaldehyde is however even more toxic than alcohol, but may, under favourable circumstances, be more safely oxidized to acetate by aldehyde dehydrogenase. However, alcohol exposure carcinogenesis involves these same enzymes, the acetaldehyde formed in the first step being the major culprit, constituting a reactive compound that forms covalent complexes with proteins and DNA and thus may act as a mutagen. Alcohol can also induce the cytochrome P450 enzyme that work with alcohol dehydrogenase to oxidize alcohol. This enzyme also forms dangerous reactive oxygen species that can activate environmental pro-carcinogens into carcinogenic forms. (Goodsell D, The Oncologist, 11(9), 2006) Acetaldehyde is one of 13 carcinogens accounting for approximately 23% of the carcinogenic effects of tobacco smoking (Sanner T, Dybing E, ‘Carcinogens in Tobacco Smoke and Quantitative Risk’, The Toxicologist, 96(1), 2007).