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?