Green Chemistry and Environmental
Health
Linda S. Birnbaum, PhD, DABT, ATSDirectorDirector
National Institute of Environmental Health Sciences and
National Toxicology ProgramResearch Triangle Park, NC, USA
Green Chemistry Panel - June 24, 2009
12 Principles of Green Chemistry
1. Pollution Prevention
2. Atom Economy
3. Less Hazardous Synthesis
4. Design Safer chemical
5. Safer Solvents & Auxillaries5. Safer Solvents & Auxillaries
6. Energy Efficiency
7. Renewable Feedstocks
8. Reduce Derivatives
9. Catalysis
10. Design for Degradation
11. Real-time Analysis
12. Accident Prevention
We All Know That Cigarette Smoke and Alcohol Are Bad For Us.
What About Other Substances in Our Environment?
Pesticides
and Toxics
UV Radiation Lead
Biologicals
Indoor Air
Mercury
Particulate
Matter
Ozone
Asbestos
Should We Be Concerned?
• How do we identify potential hazards to human health?
• How do we understand the seriousness of such hazards?
• What is Environmental Risk?
– The likelihood of injury, disease, or death resulting from exposure to a potential environmental hazard
Chemicals Migrate from Processes and Products Into
the Environment.
What Makes Environmental
Chemicals Bad For Us?
• Persistence• Persistence
• Bioaccumulation
• Toxicity
• “Dose”
• Timing
Persistence of Chemicals
• Chemicals “live” beyond their initial intended use
• Persistence determined by half-life in air, water, and soil.
• Persistence = Key Criteria in deciding if toxicity testing needed
• Need to predict persistence of a chemical BEFORE widespread • Need to predict persistence of a chemical BEFORE widespread introduction into and distribution in the environment
– Laboratory and Computational Models
• If ubiquitous, may achieve “persistence” due to continuous exposure
• Many of the chemicals we hear about are persistent, e.g., PCBs, dioxin, PBDEs, PFCs OR ubiquitous, e.g., BPA, phthalates
What is “Low Dose”?
• The "dose makes the poison" F
– Different effects occur at different doses
• “Low” Dose may just mean “lower” than usually studiedusually studied
– The most common definition: Below previously identified “adverse” dose level; environmental exposure levels; in the physiological rangeF
What about Timing of Exposure?
• People vary in their susceptibility to the toxic effects of
chemical exposures
• Early life-stages, older life
stages, those with pre-existing stages, those with pre-existing
conditions or genetic-based
vulnerabilities, people who are
more highly exposed
Increased Susceptibility Of The Developing Organism
• Rapid Growth
• Extensive Differentiation
• Opportunities for initiation of lesions and promotion of lesions and promotion of altered cells
• Development is a highly integrated process
Early Life Exposure and Adult Development
of Disease
• Many chronic adult diseases (asthma, diabetes, obesity,
heart disease) may be traced back to exposures that
occurred during development
• In utero or neonatal exposures to environmental, dietary,
and behavioral changes may make people susceptible to
diseases later in life
• Vulnerability of human fetus to outside influences (“Barker
Hypothesis”)
“Inert Ingredients” Are Not Really Inert
• Pesticide products contain both "active" and "inert" ingredients
• Inert ingredients = key to the effectiveness, but federal law does not require them to be identified by name or percentage on the label. percentage on the label.
• Not all inert ingredients are non-toxic
– Many are uncharacterized for toxicity
• NB: NOT ONLY PESTICIDES
– Drugs
– Personal Care Products
Environmental Chemicals In the News: NanoparticlesSimultaneous development of products and management of
unintentional consequences
• Internal dose in biological systems
– What physiochemical properties determine the absorption, distribution and elimination of nanomaterials?
• Early biological effects and altered structure function• Early biological effects and altered structure function
– What physiochemical properties determine biocompatibility?
• Adverse effects
– What are the critical determinants of toxicity for those that are toxic?
Poland et al
Nature
Nanotechnology
(2008)
Peritoneal
instillation of
long vs short or
tangled CNTs
induced
inflammation
and granuloma
response
(pilot study)
Production Capacity > 6.5 Billion Pounds/Year
Environmental Chemicals in the News:
BISPHENOL A
Prenatal-neonatal Exposure of Mice and Rats to
Bisphenol A at Human Exposure Levels in Relation
to Human Health Trends
Effects In Mice & Rats Human Health Trends
Abnormal urethra Abnormal penis+urethra
Prostate hyperplasia & cancer Prostate cancer increaseProstate hyperplasia & cancer Prostate cancer increaseMammary gland hyperplasia Breast cancer increase
Sperm count decrease Sperm count decrease
Early puberty in females Early sexual maturation
Hyperactivity/Impaired learning ADHD
Abnormal oocytes Miscarriage
Body weight increase Obesity increase
Environmental Chemicals In the News: DIOXIN
(Before) (After)
Viktor Viktor
Yushchenko
Recent Findings (2008 +) in People
• Dioxins and Thyroid function (Baccarelli)
• Dioxins and CVD (Humblet)
• PCBs and Hypertension (Everett)
• PCBs/DDE and Cryptochidism (Brucker-Davis)
• PCBs and Sex Ratio (Hertz-Picciottto)
• PCBs/PCDFs and Oxidative Stress (Shimizu)
Environmental Chemicals in the News:
Perfluorinated Chemicals (PFCs)
• Fully fluorinated organic chemicals, C4-C14, carboxylic acid or sulfonic acid functional group
• Man-made, exceptionally stable to metabolic and environmental degradationmetabolic and environmental degradation
• Surfactants with wide consumer and industrial applications
• Identified at ppb levels in human serum from general population and wildlife
• Rodent Carcinogens, Developmental and Reproductive Toxicants, Immunotoxicants
Environmental Chemicals In the News:
FLAME RETARDANTS
www.ewg.org
Recent Findings: PBDE Effects in People
• Cryptorchidism
– Main et al, 2007
• Reproductive Hormone Effects
– Meeker et al., 2009 –Decrease in Androgens and
• Thyroid Homeostasis
– Yuan et al, 2008 –elevated TSH
– Herbstman et al, 2008 –decrease in TT4
– Turyk et al, 2007 –Decrease in Androgens and LH; Increase in FSH and Inhibin
– Meijer et al, 2008 –Decrease in Testosterone
• Decreased Sperm Quality
– Akutse et al, 2008
• Diabetes
– Lim et al, 2008
– Turyk et al, 2007 –elevated T4
– Meeker et al, 2009 –elevated T4, TBG
– Dallaire et al, 2009 –elevated T3 ~BDE47
What do Many of these Chemicals have in
Common?
“Endocrine Disruptors”
Exogenous agents that interfere with the production, release, transport, the production, release, transport, metabolism, binding, action, or elimination of the natural hormones in the body responsible for the maintenance of homeostasis and the regulation of developmental processes
Fa “new” type of toxicity
Decreases
Exposure to Endocrine Disruptors:
Effects in Wildlife (Fish, Frogs, Reptiles And Birds)
• Survival
• Immune system - resistance to disease
• Size of thyroid
• Size of liver
• Abnormal testes and ovaries
• Spontaneous abortions
• Abnormal sexual behavior
• Thyroid hormones
• Estrogen - ovarian hormones
• Androgen - testicular hormones
Increases
Disruption
HERBICIDES
2,4,-D
2,4,5,-T
Alachlor
Amitrole
Atrazine
Linuron
Metribuzin
Nitrofen
Trifluralin
INSECTICIDES
Aldicarb
beta-HCH
Carbaryl
Chlordane
Chlordecone
DBCP
Dicofol
Dieldrin
DDT and metabolites
INDUSTRIAL CHEMICALS
Bisphenol - A
Polycarbonates
Butylhydroxyanisole (BHA)
Cadmium
Chloro- & Bromo-diphenyl
Dioxins
Furans
Lead
Manganese
Endocrine Disrupting Chemicals
Trifluralin
FUNGICIDES
Benomyl
Ethylene thiourea
Fenarimol
Hexachlorobenzene
Mancozeb
Maneb
Metiram - complex
Tri-butyl-tin
Vinclozolin
Zineb
METALS
DDT and metabolites
Endosulfan
Heptachlor / H-epoxide
Lindane (gamma-HCH)
Malathion
Methomyl
Methoxychlor
Oxychlordane
Parathion
Synthetic pyrethroids
Transnonachlor
Toxaphene
Manganese
Methyl mercury
Nonylphenol
Octylphenol
PBDEs
PCBs
Pentachlorophenol
Penta- to Nonylphenols
Perchlorate
PFOA
p-tert-Pentylphenol
Phthalates
Styrene
Testosterone synthesis inhibitor Estrogen receptor agonist
Thyroid hormone disruptor Androgen receptor antagonist
• Humans are always exposed to multiple chemicals
• It is difficult to decipher how exposure to many chemicals will influence the effects of each
Chemical Mixtures
will influence the effects of each one – both in time and space
• There is no such thing as being unexposed
• What does the CDC “report card” mean?
HUMAN
HEALTH & DISEASE
Risk Paradigm
TIME
HEALTH & DISEASE
ExposureInternal
Dose
Early
Biological
Effect
Altered
Structure/
Function
Adverse
EffectSources
Thank you!
Questions?