Grand Teton National Park, WY. Next door to Yellowstone Park. Dramatic mountain views. Famous for winter skiing, summer hiking.

MID-TERM EXAMINATION Wednesday 18 MARCH The Armageddon Chemical Company wants to market a new product, Malodorex which can be added to fabrics of all kinds, and which will prevent unpleasant odors by killing molds and algae in all products that contain it, including – but not limited to - running shoes, socks, towels, swimming suits. It is known that about 5% of Malodorex comes out of fabrics each time they are washed. Assume that you are the US EPA regulator charged with making sure that products containing Malodorex do not harm humans or the environment. Based on information acquired in this course or elsewhere: What tests do you ask the company to run, and why? (Assume that Congress worries that EPA is over-regulating industry, so you must justify every test you require.)

Conditions for the Midterm You may use any sources you wish to prepare for the exam. On 3/18, you may not bring any notes or information with you. I will provide paper for the exam, which may be written as an essay or as “bullet points”. Necessary information consists of –tests that need to be run –why the particular test is needed It is not necessary to describe the test in detail; identifying it is enough. If you choose to use “bullet points” (the format of this slide), be sure you connect each specific test with the reasons it is necessary. You may also list tests that are not necessary, and explain why they need not be run. (This will show Congress you are not over- regulating.)

GRADING You will be graded on: – the appropriateness of the tests you require –the appropriateness of the rationale If you include tests that need not be run, you will be graded on: –whether these tests are really unnecessary –the correctness of the rationale for this decision. Grading will be in the form of letter grades, A-F. There will be no deductions for grammar or syntax (“style”), but if I cannot identify a badly misspelled word, you may lose credit because I misinterpret your answer.

Perfluorinated Compounds: The saga of PFOS (aka Scotchgard  )

PFOS-Generating Polyfluorinated Compounds Inert ingredient in pesticide formulations

Perfluorooctanesulfonamide: PFOSA Precursor for PFOS. Uncouples oxidative phosphorylation

PFOS or perfluorooctane sulfonate – key ingredient in “Scotchgard”. Usually exists as a salt Half life in humans: 5.4 years

Precursor chemical for Gore-tex, teflon Persists “indefinitely” in the environment. Carcinogenic, nephrotoxic (animal studies); found in 98% of people in US. Occupational epidemiology study suggests it causes mesothelioma, diabetes, kidney cancer, testicular cancer, ulcerative colitis, thyroid disease, hypercholesterolemia, and pregnancy-induced hypertension PFOA: Perfluorooctanoic acid

Teflon Perfluoroalkoxy- polymer resin Polytetrafluoroethylene Extremely inert. Decomposes above 200°C; products are lethal to birds, and cause flu-like symptoms in humans.

Uses of Perfluorinated Compounds Post-its New clothing –Wash at least 6x to remove Water-resistant clothing Tyvek suits Blue Ice Wrappers for –Microwave popcorn –Fast food Chicken sandwiches French fries –Pizza –Beverages –Candy, candy bars –Cookies Stain repellant on –Carpets, furniture Decorative pillows Fabric wall coverings Outdoor furniture Bed coverings Mattress pads Shower curtains Photographic products Sportswear Backpacks, tents Clothing Shoes, handbags

People and Agencies 3M: Minnesota Metallurgy and Mining –Makers of Scotch tape, Scotchgard, Posteds, etc –Personnel: Patsy Sherman, inventor Rich Purdy, eco-toxicologist MCPA: Minnesota Pollution Control Agency –Similar to IL EPA and IL Pollution Control Board –Personnel Fardin Oliaei, eco-toxicologist US Environmental Protection Agency –Regulatory and research functions OSHA: Occupational Safety and Health Administration Superfund –Law and policies regulating cleanup of hazardous wastes

History - Part 1 “ Better living through chemistry ” 1953 –Patsy Sherman spills ‘ synthetic latex ’ on colleague ’ s sneaker 3M scientist Spill could not be removed by scrubbing, soap and water, solvents 1956 –3M introduces Scotchgard  fabric protector

History - Part 2: Company Tales 1978 –Perfluorinated chemicals present in workers ’ blood 3M learns of this from sampling 1981 –Perfluorinated compounds shown to be toxic to rhesus monkeys –3M hires environmental toxicologist Examines environmental effects of Scotchgard  and related compounds 1997 –PFOS and PFOA found in blood supply –3M expands testing to wildlife, human toxicities 1999 –3M has sufficient evidence to show that PFOS, PFOA are toxic, persist in environment, bioaccumulate in food chain

History - Part 3 There ’ s just one small problem… February 2000 –Purdy quits 3M Because 3M has not reported findings to EPA? May 2000 –3M announces it will phase out Scotchgard  “ Principles of responsible environmental management ” MPCA [Minnesota Pollution Control Agency] does not pursue issues of –Contamination of 3M plants in MN –Contamination at 3M waste disposal sites –Federal EPA investigates

History - Part 4: All the king ’ s horses and all the king ’ s men 2001: Independent research published –John Giesy, MSU PFOS is everywhere –Fardin Oliaei & UM researchers Voyageurs National Park –50% of fish are contaminated with perfluorinated chemicals 2002: Occupational safety and health issues –Decatur, AL workers sue 3M for occupational illnesses –3M phases out PFOS production in MN 10,000 lbs fluorocarbon compounds went into Mississippi R in 2001 –Drinking water in MN is contaminated with PFOS, PFOA 2002: Politics –MN governor appoints 3M employee as MPCA commissioner

How it Looks Today CDC added PFOS, PFOA to NHANES –the national biomonitoring surveillance study 3M study shows children and adults have similar levels of PFOS- related chemicals in blood –Argues for transplacental passage Ongoing investigations of contamination at 3M plants –Lawsuits by townships, property owners, workers

Why Fuss? Ubiquity –Kannan et al, 2002 Oysters in Chesapeake Bay, Gulf of Mexico PFOS present in oysters at 51 of 77 locations < 42 ppb to 1.2 ppm –Even found in polar mammals Health effects in lab animals –Liver damage –Developmental toxicity Half-life in humans – days Half-life in the environment?

Developmental Toxicity Study: Case, York and Christian, 2001 –PFOS and related N-EtFOSE –Rats and rabbits –Classical prenatal “ teratology ” study 1, 5, 10, 20 mg/kg/d, GD 6-17 in rats 0.1, 1, 2.5, 3.75 mg/kg/d, GD 7-20 –Results: Fetuses are damaged only at doses that are very toxic to the dam Not a “ classical teratogen ” Not selectively toxic to the fetus

Developmental Toxicity: Crasty, Grey, Lau & Rogers, 2003; Lau, Butenhoff & Rogers, 2004 PFOS treatment near the end of gestation causes postnatal mortality –25 mg/kg/day --->34% mortality by 5 days –Failure of lung maturation suspected as cause of death –Weight reductions in surviving pups –Delayed onset of puberty in survivors

What is the Question? Does PFOS cause malformations at levels that don ’t cause toxicity in adults? –NO Does PFOS affect development at levels that don’t cause toxicity in adults? –YES

PFOSA: precursor for PFOS. Uncouples oxidative phosphorylation PFOS: key ingredient in “Scotchgard” Half-life in humans: 5.4 years Precursor chemical for Gore-tex, teflon. Persists “indefinitely” in the environment. Carcinogenic, nephrotoxic (animal studies); found in 98% of people in US.

The new Scotchgard™ Perfluorobutanesulfonic acid Half life in humans = 30 day

NITROFEN

Brief History of Nitrofen 1966: First registered in U.S. 1971: Ambrose et al: Neonatal mortality at 100 ppm in maternal diet 1974: Kimbrough et al, Arch. Environ. Health: Neonatal mortality confirmed 1981: Costlow and Manson: Heart and lung defects identified 1981: Withdrawn from all U.S. uses

Toxicity of Nitrofen in Rats Adult toxicity –LD 50 > 1 g/kg –Adverse effect at LOAEL: liver enlargement Fetal toxicity –NOAEL: < 0.1 mg/kg/day –Adverse effect at LOAEL: diaphragmatic hernias –Other: heart, lung, kidney defects; cleft palate. This is a chemical that is selectively toxic to the fetus!

Lesson Learned? It is necessary to have data -- but it is not sufficient! It is also important to think about the data. –R. Kimbrough was at US EPA (research division) when she ran experiments on nitrofen –She did not recognize the importance of neonatal deaths. –EPA regulators had access to Ambrose ’ s article - it was in the top tox journal. They missed its importance. –To be fair, in early the 1970s, most of the emphasis was on physical malformations rather than on the broader category of “ developmental toxicity.

Grand Tetons