Ethics Toxicity Ecotoxicity Persistence Bioaccumulation and Green Chemistry

Ethics, Toxicity, Ecotoxicity, Persistence, Bioaccumulation and Green Chemistry Terry Collins Central Catholic High School, September 21, 2005, Pittsburgh PA

Western Civilization is not sustainable as it is currently constituted — flawed technologies are an important component of the sustainability dilemma

“Altered Nature of Human Action” “All previous ethics…[have been based upon the premises]…that the human condition, determined by the nature of man and the nature of things, was given once for all; that the human good on that basis was readily determinable; and that the range of human action and therefore responsibility was narrowly circumscribed. … [But] with certain development of our powers the nature of human action has changed, and … [given rise to] … a whole new dimension of ethical relevance for which there is no precedent in the standards and canons of traditional ethics. ” The Imperative of Responsibility: Finding an Ethics for the Technological Age, Hans Jonas, U. Chic. Press, 1984

The altered, always enlarged nature of human action, with the magnitude and novelty of its works and their impact on man’s global future, raises more issues for which past ethics, geared to the direct dealings of man with his fellow men within narrow horizons of space and time, has left us unprepared. A new reflection on ethical principles—including such that, for lack of application, could hitherto remain silent—is required for coping with those issues. The Imperative of Responsibility: Finding an Ethics for the Technological Age, Hans Jonas, U. Chic. Press, 1984

The lengthened reach of our deeds moves responsibility, with no less than man’s fate for its object, into the center of the ethical stage. Accordingly, a theory of responsibility, lacking so far, is set forth for both the private and the public sphere. Its axiom is that responsibility is a correlate of power and must be commensurate with the latter’s scope and that of its exercise. For its discharge today, therefore, we need lengthened foresight, that is, scientific futurology. The Imperative of Responsibility: Finding an Ethics for the Technological Age, Hans Jonas, U. Chic. Press, 1984

Even at its best, however, such an extrapolation from presently available data will always, in certainty of prediction, fall short of the causal pregnancy of our technological deeds. Consequently, an imaginative “heuristics of fear” replacing the former projections of hope, must tell us what is possibly at stake and what we must beware of. The magnitude of those stakes, taken together with the insufficiency of our predictive knowledge, leads to the pragmatic rule to give the prophecy of doom priority over the prophecy of bliss. The Imperative of Responsibility: Finding an Ethics for the Technological Age, Hans Jonas, U. Chic. Press, 1984

What we must avoid at all cost, is determined by what we must preserve at all cost, and this in turn is predicated on the “image of man” we entertain. Formerly, this image was enshrined in the teachings of revealed religions. With their eclipse today, secular reason must base the normative concept of man on a cogent, at least persuasive, doctrine of general being: metaphysics [the branch of philosophy that examines the nature of reality] must underpin ethics. Hence, a speculative attempt is made at such underpinning of man’s duty to himself, his distant posterity, and the plenitude of terrestrial life under his dominion. That attempt must brave the veto of reigning analytical theory against all attempts of this kind and indeed cannot hope for more than a tentative result. But dare it we must. A philosophy of nature is to bridge the alleged chasm between scientifically ascertainable “is” and morally binding “ought”. The Imperative of Responsibility: Finding an Ethics for the Technological Age, Hans Jonas, U. Chic. Press, 1984

The thus-gained conception of objective imperatives for man in the scheme of things enables us to discriminate between legitimate and illegitimate goal-settings to our Promethian [boldly creative or defiantly original in behavior or actions] power (a distinction encompassing but surpassing that between realistic and unrealistic goals). This discrimination is elaborated in assessing the potentials of “progress” up to the most ambitious idea of it— contemporary utopianism as represented by the Marxian alliance with technology. Against the immodesty of its goals, which maximize the inherent dangers of overstraining nature, the more modest and fitting goal is set to save the survival and humanity of man from the excesses of his own power. The Imperative of Responsibility: Finding an Ethics for the Technological Age, Hans Jonas, U. Chic. Press, 1984

“A whole new dimension of ethical relevance” The Imperative of Responsibility: Finding an Ethics for the Technological Age, Hans Jonas, U. Chic. Press, 1984 • Today, because of science and technology, individual power projects into both time and space much further than ever before. • Ethics is about the forces that guide human action. Science, especially chemistry, has become completely intertwined with human action. Accurate analysis of any human action in the developed world is impossible absent an examination the influence of chemistry on that action, from the way we communicate, educate ourselves, feed ourselves, protect our health, and even to the way we procreate. • Ethical principles need to be reinterpreted to recognize the reality of the vast power we now have over life and the environment because of science and technology. • Thus, chemistry is inextricably intertwined with ethics! A healthy education in chemistry should contain a significant analysis of sustainability ethics.

The idea that our civilization is not sustainable, now broadly accepted in a growing consensus, implies that someone is responsible for fixing things. If unsustainable technologies are part of the problem, the technical leadership is clearly responsible for fixing this part. • The leadership must first ask, for each identified problem, if solutions are conceivable. • If the answer is affirmative, the responsibility of the leadership translates into a duty to engage energetically in finding the solutions. • If the answer is negative, their responsibility translates into a duty to alert the civilization to move away from the dependence that is undermining it.

The Fundamental Green Chemistry Concept Risk = f 1(exposure) f 2(hazard) Paul Anastas and John Warner

To teach green chemistry properly, green chemists must develop an adequate understanding of toxicity and ecotoxicity [of f 2(hazard)] and incorporate this into the basic course material of chemistry. T, J. Collins, The Importance of Sustainability Ethics, Toxicity and Ecotoxicity in Chemical Education and Research, Green Chemistry, 2003 (August), G 51 -G 52

Safe Energy New chemistry for solar-to-electrical or solar-tochemical energy conversions Renewable Feedstocks The Chemical Goals for Sustainability Pollution Reduction Economical feedstocks for chemical and polymer industries from plants Move the elemental composition of technology closer to biochemistry to eliminate persistent environmentally mobile pollutants

Solar Stirling Engines

Solar Stirling Engines

Solar Stirling Engines

The stakes of failing to address toxicity and ecotoxicity are incredibly high.

• Decrease in anogenital distance among male infants with prenatal phthalate exposure, Shanna Swan et al. , Environmental Health Perspectives on-line May 27, 2005 • Exposure to methoxychlor and vinclozolin produces male reproductive problems down 4 generations, Michael Skinner et al. , Science 2005, 308, 1391 -1392 • Perinatal exposure to low levels of the environmental anti-androgen vinclozolin alters sex-differentiated social play and sexual behaviors in the rat, Vincent Markowski, et al. , Environmental Health Perspectives, 2005, 113, 700 -707 • Use of di(2 -diethylhexyl)phthalate-containing medical products and urinary levels of mono(2 diethylhexylphthalate) in neonatal intensive care units, Howard Hu et al. , Environmental Health Perspectives, on-line, June 10, 2005.

Exposure to anti-androgen, Flutamide Percentage of offspring affected 100 Males with areolae 75 Hypospadias 50 25 16 Courtesy of J. Peterson Myers Small prostate Abnormal seminal vesicles Abnormal bladder 17 18 19 Day of exposure after conception Paul Foster and Martha Harris, Toxicol Sci, 2005, 1591

How might chemists learn how to avoid known toxicity/ecotoxicity in the design of new products and processes? • Historical analyses building from the anecdotal, to the epidemiology, to the molecular level understanding — importance. • Toxicity testing as an integral component of chemical research — guidance. • More interdisciplinary research involving chemists and toxicologists — synergy. • An outright rejection of “spin” — obligation.

Discovery of Lead Toxicity “Sweet Poison” Josef Eisinger Natural History, 7/96 Goslar The Bastion of Ulm

Evidence belies the idea that Pb is part of the natural human intake!

Lead Poisoning May Have Doomed Beethoven A house painter affected by chronic lead poisoning. Wasted muscles and wrist-drop are tell-tale symptoms of lead poisoning.

Lead Industry Advertises through Children The cover of the National Lead Company’s trade magazine conveys the message that children can be encouraged to use lead paint safely on toys. (Dutch Boy Painter, December 1928) “Deceit and Denial”, Markowitz and Rosner

Lead Industry Advertises through Children Even after WWII, lead was promoted as a boon to children. Here, National Lead tells parents that lead solder is not a problem, even in canning evaporated milk meant for babies. (Saturday Evening Post, February 23, 1946) “Deceit and Denial”, Markowitz and Rosner

Some People of Lead “Deceit and Denial”, History Markowitz and Rosner • Felix Wormser, General Secretary Lead Industries Association (LIA) from 1928 to 1947, led the industry’s battle against negative publicity. • Joseph Aub, Harvard University Lead Researcher supported by LIA, regularly underplayed lead paint toxicity. • Robert Kehoe, University of Cincinnati Kettering Labs physiologist who helped formulate the lead industries position on toxicity of Pb. Et 4—Aub and Kehoe dominated lead toxicity research for three decades from the 1920 s. • Herbert Needleman, academic pediatrician at Children’s Hospital in Philadelphia, later psychiatrist at Harvard and then University of Pittsburgh, leader in showing toxic effects of low level lead in children.

Metabolism of Lead in Humans Environmental Toxicology: Biological and Health Effects of Pollutants, 2 nd Edn. Ming-Ho Yu, CRC Press, Boca Raton 2005 Lead ingested (20 -400 mg/day) Skeleton (90%) t 1/2 ≈ 25 years (Estimate: 20– 400 mg/day) GI tract (≈92% adult, ≈75% children) Lead inhaled (≈8% adult, ≈25% children, perhaps 50%) Blood Lungs Soft tissues (liver, brain, pancreas, kidneys, bone marrow) t 1/2 ≈ 40 days Kidney Feces Urine Lead is a systemic poison

National BLLs BLL above 10 mg/d. L (% children) Casarett and Doull’s Toxicology: the basic science of poisons, 6 th Edn. Curtis D. Klassen, Mc. Graw-Hill, New York, 2001 Age of residence (year built) Nearly a million US children are at risk from lead poisoning (BLLs > 10 mg. d. L-1) and specific groups of children are at greatest risk.

Biological Effects of Lead Environmental Toxicology: Biological and Health Effects of Pollutants, 2 nd Edn. Ming-Ho Yu, CRC Press, Boca Raton 2005 • in plants, Pb inhibits electron transport in corn mitochondria, depresses respiratory rate in germinating seeds, and inhibits various enzyme systems. • Pb has a high affinity for the sulfhydryl group (–SH). Enzymes with function dependent upon the –SH group may be inhibited by mercaptide formation leading to inactivation. 2 RSH + Pb 2+ ® RS–Pb–SR + 2 H+ eg’s: adenyl cyclase: catalyzes conversion of ATP to cyclic AMP needed in brain neurotransmission, aminotransferase involved in transamination, important in protein metabolism • in mammals, Pb 2+ can compete with Ca 2+ for entry at the presynaptic receptor — because Ca 2+ evokes release of acetylcholine (ACh) across the synapse, inhibition induces a decreased end-plate potential. The miniature end-plate potential release of sub-threshold levels of ACh is increased. • adverse effects on nucleic acids leading to decreased or increased protein synthesis. • Pb decreases aminoacid acceptance by t. RNA and the ability of t. RNA to bind to the ribosome • Pb causes dissociation of ribosomes • Pb inhibits ALAD and ferrochelatase — both involved in heme biosynthesis — ferrochelatase catalyzes the incorporation of Fe 2+ into protophyrin IX

Scheme of Heme Biosynthesis Showing Sites Where Pb Has an Effect Casarett and Doull’s Toxicology: the basic science of poisons, 6 th Edn. Curtis D. Klassen, Mc. Graw-Hill, New York, 2001 Cytoplasm Mitochondrion Pb Heme + Fe 2+ Cytochrome C Pb Succinyl Co. A + glycine Fe 2+ ALA synthetase ALA-S Protoporphyrin IX Ferrochelatase + Pb Heme Oxidase microsomal Bilirubin + Fe Copro III Coproporphyrinogen oxidase Coproporphyrinogen III Uroporphyrinogen I d-aminolevulinic acid (ALA) Pb ALA dehydratase ALA-D Porphobilinogen (PBG) Pb Site of Pb inhibition

Reproductive Toxicology of Lead Principles of Toxicology. Karen F. Stine & Thomas M. Brown, CRC Press, Boca Raton 1996 MALE • Pb 2+ (also Cd 2+) are well known reproductive toxicants — exposure has been associated with infertility and chromosomal damage in sperm. • Cd 2+ can cause testicular necrosis, probably by decreasing blood flow to the testes. • Other male reproductive toxicants include: – ethanol, which causes delay in testicular development and may effect supporting cells – the pesticides, kepone and DDT, the solvent, CS 2, and tobacco smoke (smokers have a higher % of abnormal sperm cells than non-smokers). FEMALE • Pb poisoning associated with reduced fertility, miscarriages and stillbirth since antiquity • cytotoxic substances such as antineoplastic agents, heavy metals, polycyclic aromatic hydrocarbons (PAHs), or radiation may damage oocytes, particularly in adult women. • some cytotoxic substances, e. g. , PAHs, must be metabolized to produce toxicity — the activation can take place via cytochrome P 450 in the ovaries (epoxide formation). Toxic PAH metabolites destroy primary oocytes, providing one explanation for the observation that smoking may lead to early menopause. • other toxicants include pesticides, chlorinated hydrocarbons, and aromatic solvents

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Peroxidase Mimics first effective peroxideusing enzyme mimics Mechanism detailed understanding of catalytic mechanism High Oxidation state Chemistry synthesis and characterization of rare or unprecedented species Water Cleaning chlorinated pollutants, antibiotics, phenols destruction Oxygen Chemistry direct reaction of oxygen with ferric ion Biological Warfare Rapid destruction of anthrax-like spores Pesticides Decon major class (thiophosphates) rapidly-completely destroyed Laundry dye transfer inhibition, stain removal Textiles dye bleaching, effluent decolorization Pulp and Paper pulp bleaching, effluent smell, organochlorine and color removal Pharmaceuticals Decon trace pharmaceuticals removed from water supply Drinking Water Disinfection safer drinking water free of chlorinated disinfection byproducts Agricultural animal husbandry, renewable feedstocks Chemical Warfare rapid destruction of chemical warfare agents Petroleum Refining removal of sulfur contaminants in diesel & gasoline Others metal refining, carpet recycling, hospital disinfection