1. Michigan Department of Health and Human Services (MDHHS)
Deb Mackenzie-Taylor, PhD
Division of Environmental Health

2. MDHHS’s Role = Provide Technical Support to Local Health
Evaluate potential exposures to environmental chemicals
Determine if harm may occur
Provide recommendations
Outreach to public, healthcare, others
Determine if exposure is or may become complete
If the exposure level (dose) may be harmful
Recommendations
It is not likely to be harmful – but recognize concern can cause harm in the form of stress – still provide options to limit or prevent exposure for the individual
It may be harmful – may provide recommendations to local health departments (and other agencies) to take actions to limit or prevent exposure (e.g. alternative drinking water supply or filter) or may be recommendations that the individual can take themselves (e.g. limit type and/or quantity of fish meals - eat safe fish)
May be meetings, brochures, factsheets, reports, advisories

3. Assessing risk Amount of people’s exposure (dose)
Chemical concentrations in environmental media
Amount of people’s exposure (dose)
Toxicity of chemicals
Risk or hazard from the exposure
Need to know what chemicals hazards are present at what concentrations
If people may be exposed, how they may be exposed, and at what level/dose (upper percentile exposure, may be susceptible sub-population)
What are potential health outcomes at different doses and routes, focus on most sensitive health outcome/ lowest dose and uncertainty/variability to be considered with that dose
Compare exposure dose to toxicity dose to determine risk
Merged the 4 steps of risk assessment with an exposure pathway
Risk Assessment Process:
Hazard Identification
Hazard Evaluation or Dose-Response Assessment
Exposure Assessment
Risk Characterization
Exposure pathway:
Source
Environmental Transport and Media
Exposure Point
Exposure Route
Exposed Population
Time Frame
Status – completed, potential, not completed

4. Evaluating toxicity of chemicals
Evaluation includes:
Information from human epidemiology studies
May find associations with diseases or cancers
Exposure levels have varying levels of uncertainty (dose- response may not be available)
Information from laboratory animal studies
Do human and laboratory animals have similar health outcomes?
Are health outcomes biologically possible in humans?
Dose-response data used to develop toxicity values
Since we don’t intentionally dose people with industrial chemicals to study the effects, only rare cases where sufficient data to determine cause and effect or dose response – only associations
Laboratory animals – typically rodents with minimal genetic diversity as compared to human population

5. PFAS Toxicology PFOA and PFOS Other PFAS
Used in a wide variety of products in the past
Many published studies focusing on these two PFAS
Other PFAS
Many other per- and polyfluorinated alkyl substances (PFAS) in products and the environment
Limited number of published studies on some other PFAS (no studies on others)
Fairly unique properties - repellant to water and fat, reduce friction, surfactants so widely used

6. Health Outcomes (PFOS and PFOA)
In people:
In laboratory animals:
Alter cholesterol
Thyroid disease (PFOA)
Ulcerative colitis (PFOA)
Testicular and kidney cancer (PFOA)
Alter immune system function
Developmental effects
Reduce ossification of the proximal phalanges
Decrease pup birth weight
Accelerated puberty in male pups
Immune system dysfunction
Alter liver and kidney weight
Health Outcomes with strongest weight of evidence with existing studies
A variety of health endpoints have been examined in people and laboratory animals exposed to PFOA and PFOS.
People are also exposed to many PFAS in a variety of products. Laboratory animal studies were used to develop the lifetime health advisories for PFOA+PFOS.
In people:
Alter cholesterol (C8/PFOA study – link with high cholesterol)
Thyroid disease (C8/PFOA study)
Ulcerative colitis (C8/PFOA study)
Pregnancy-induced hypertension (C8/PFOA study)
Testicular and kidney cancer (C8/PFOA study)
Alter immune system function (NTP monograph – PFOA and PFOS suppresses antibody response, high level of animal data and moderate level of human data)
C8/PFOA study – no probable link – diagnosed hypertension, coronary artery disease, chronic kidney disease, liver disease, osteoarthritis, Parkinson’s disease, autoimmune diseases (rheumatoid arthritis, lupus, type1 diabetes, Crohn’s disease, or multiple sclerosis), common infections (including influenza), neurodevelopmental disorders in children – including attention deficit disorders and learning disabilities, asthma or chronic obstructive airways disease, stroke, type II (adult-onset) diabetes, birth defects, miscarriage and stillbirth, preterm birth or low birth weight
In lab animals – monkeys, rats, and mice:
Developmental effects
Reduce ossification of the proximal phalanges (PFOA exposure during gestation and lactation in rats – basis of PFOA RfD)
Decrease pup birth weight (PFOS exposure during gestation and lactation in rats – basis of PFOS RfD)
Accelerated puberty in male pups (PFOA exposure during gestation and lactation in rats – basis of PFOA RfD)
Immune system dysfunction
Alter liver and kidney weight

7. EPA’s Health Advisory Levels
Based on reference doses (RfD) derived from developmental toxicity study in mice (PFOA) and rats (PFOS)
“Lifetime” Health Advisory
PFOA + PFOS = 70 ppt (ng/L)
Short-term and long-term exposure
Protects fetus and others against noncancer health effects (also protective against development of cancer)
Considers exposure to other sources/routes (e.g., household products)
Suggestive Evidence of Carcinogenic Potential for PFOA
EPA estimated CSF of 0.07 (mg/kg/day)^-1 for PFOA based on testicular tumors in rats and the lifetime health advisory is protective of the cancer endpoint
Suggestive Evidence of Carcinogenic Potential for PFOS
Not enough data for a quantitative cancer assessment (no dose-response relationship out of the one rat study available)
Are the health advisory levels appropriate for all children (regardless of age)?
Yes, the 70 parts per trillion health advisory levels offer a margin of protection for children regardless of age. The health advisory levels are based on developmental effects to a fetus or breastfed infant resulting from exposures that occur during pregnancy and lactation (nursing) and are also protective, over a lifetime of exposure to drinking water at these levels, for all other health effects (non-cancer and cancer).

8. More Information
Deb Mackenzie-Taylor, PhD, MDHHS Toxicology and Response Section Manager

10. Non-Cancer Risk Increasing Population Risk
Sensitive populations might be at risk for health effects
Exposure to an amount higher than the toxicity value (Reference Dose)
Increasing
Population Risk
Exposure equivalent to the toxicity value (RfD)
Minimal Risk
Zero Risk
Zero Exposure

11. Blood Testing PFAS are in many products commonly used
People are expected to have some level of PFAS in their blood
Blood testing:
CAN tell you the concentration in your blood at time of test
CANNOT tell you if current or future health conditions are due to PFAS or how you were exposed (where the PFAS came from)

12. Blood Levels of the Most Common PFAS in People in the United States from 2000-2014
Since 2002, production and use of PFOS and PFOA in the United States have declined. As the use of some PFAS has declined, some blood PFAS levels have gone down as well.
• From 1999 – 2014, blood PFOS levels have declined by more than 80%.
• From 1999 – 2014, blood PFOA levels have declined by more than 60%.
However, as PFOS and PFOA are phased out and replaced, people may be exposed to other PFAS.

13. Average Blood Level of Some PFAS after Installing a Water Filtration System
Blood PFAS levels decreased in people exposed to PFAS in drinking water after a water filtration system was installed.
In the mid-2000s, water sampling found PFAS contamination in municipal drinking water sources east of St. Paul, Minnesota. In 2006, a water filtration system was installed to reduce PFAS levels. PFOS and PFOA were reduced in the drinking water below the current EPA lifetime health advisory level for PFOS+PFOA of 70 parts per trillion.
In 2008, 2010, and 2014, the Minnesota Department of Health measured blood PFAS levels in people who had been exposed to PFAS in their drinking water before installation of the filtration system.
• PFOS, PFOA, and PFHxS blood levels went down in long-term residents after a water filtration system was installed.

14. Blood Levels in People Who Were Exposed to PFOA
Laboratory animal average serum levels that correspond to LOAELS: 12.4 to 87.9 milligram/liter (mg/L)
(U.S. EPA Health Effects Support Document, Table 4-8)
Biomonitoring Studies have measured PFAS levels in other groups:
• Workers in PFAS manufacturing facilities,
• Communities with contaminated drinking water, and
• The general U.S. population.
The figures below show PFOA and PFOS levels measured in different exposed populations, compared to levels CDC measured in the general U.S. population in and

15. Blood Levels in People Who Were Exposed to PFOS
Laboratory animal average serum levels that correspond to
NOAELs: 6.26 to 38 milligram/liter (mg/L)
LOAELS: 19.9 to 157 mg/L
(U.S. EPA Health Effects Support Document, Table 4-6)

16. Individual Risk
Will a specific person develop cancer or some other health effects from a chemical exposure?
There is no way for us to know.
Individual health status best evaluated by a medical doctor
Individual risk depends on other exposures, genetics, organ system functioning, health/nutritional status, and other complex parameters.

17. Population Risk (Example)
Population with low or no exposure.
Population with elevated exposure.
No way to know who would be in the shaded areas.

18. Sequence of Chemical Exposure to Disease
Effects
Susceptibility
Source
Internal Effective Dose
Early Molecular Cellular Effects
Altered Structure/Function
Clinical Diagnosed Disease
The path of chemical exposure to disease starts with a chemical entering into a person’s body, at that point you have a completed exposure pathway. Anything short of a completed chemical exposure pathway cannot cause disease. These chemicals have no purpose in a persons body, however, for the chemical exposure, to cause any harm it must reach an internal effective dose. This is an amount of chemical that can cause some time of measurable change in the human body. Initial interactions between a chemical and persons body will occur at a molecular/cellular level, and may result in changes in transcription and translation rates of RNA or protein creation, or alteration in hormone levels (dioxin –thyroid hormones, reproductive hormones). This can lead, in some people, altered structure and function of tissues or organs. Most recent example is the January 2008 Seveso paper, (describe Seveso), people exposed as children (1-9 years) having reduced sperm function and quantity as adults. It was a permanent change in testicular function. Altered tissue or organ function may not necessary result in symptoms that cause people to see their doctors. Also, it may take many years between the time of the exposure and when altered tissue and organ functions occur. To Reach a situation of a clinically diagnosed disease assumes that medical doctors have knowledge about chemical exposure and the symptoms to expect and the disease that may occur. For many chemicals, such as dioxins, PCBs, DDT, the diseases and symptoms are not unique to those chemicals. These disease, such a reproductive function, heart disease, cancer, neurobehavioral changes, are a combination of environmental factors, a person’s genetics, and current health.
Thus the answer to this situation, from a public health perspective, is either preventing exposures or limiting those exposures such that effective doses are not expected to be reached.
Symptoms
Cause?
Chemical?
Reversible?
Measurable?
Tissue
Organ
Organ System