Reference Dose

maximum tolerated dose

because experiments are expensive, this will be given to rodents to see if there is a response, often higher than what humans are actually exposed to→ get really sick and maybe that is why they got cancer and not due to exposure alone we extrapolate over large doses

confounder vs. effect modifiers

confounder: related to exposure and the outcome effect modifier: not associated with exposure magnitude of change in terms of odds ratio or relative risk ex. radon is the 2nd leading cause of lung cancer (basements + ground water)

reference dose

estimate of the daily acute or chronic exposure that is likely to be without risk of adverse effects - use for noncancer risk assessment Obtain NOAEL threshold and then put in additional safety factors on (divide by these). Total uncertainty factor is usually a factor of ten for interspecies extrapolation, as well as considering children to adult conversion. RfD = NOAEL, LOAEL, or benchmark dose/ UF x MF UF=uncertainty factor (interspecies extrapolation, variability within human population, using less than chronic data, using LOAEL instead of NOAEL and MF = modifying Factor for children (1-10) Uncertainty Factors: 10= interspecies extrapolation 10= Variability within human population (IntrAspecies) 10= Using less than chronic data* 10 = Using LOAEL, instead of NOAEL *Chronic = years vs. Acute = fast, quick, short *Infections from infectious diseases= acute; Type 2 diabetes= Chronic

establishing a reference exposure level for air

health based benchmark dose used to estimate environmental concentration consists with exposure at the reference dose, toxicological studies used to identify environmental concentrations that are unlikely to result in adverse effects, incorporates similar protections as RfD

REL

incorporates similar protections as Reference Dose REL= the specific chemical level in a room (Concentration) Health based benchmark dose used to environ concentration consistent with exposure at the RfD →Reference exposure level or air →Estimate exposure level in environment consistent w exposure at ref dose →Rox studies to identify enviro exp levels that unlikely to cause adverse effects →Incorporates similar protections as Rfd HQ for approach 2: →HQ= Ratio of measured enviro level (Exposure air concentration mg/m^3) / (REL mg/m^3) →Typical benchmarks : REL - acute REL - 8 hour cREL- chronic RfC- EPA reference concentration

the epidemiologic transition

increase in chronic disease look @ caihla's chart on study guide

cancer risk assessment

non-cancer response: no effect with little exposure, more toxic effect with more exposure, get asymptomatic at top s more once really sick won't make a difference with cancer: assume linear and the intercept is zero, no threshold compare to NSRL →Threshold for concern example: 10mg/kg/day x .01 cancer/1mg/kg/day = 10% (10^-1)→ typically like risks in range of 10^-5 (Prop 65) or 10^-6) EPA →Acceptable risk level in CA 1/100,000 →Lifetime exposure risk= mg/kg w/ 10^-5 risk →So risk/potency

RfC

reference air concentration

analytic/experimental epidemiology

tests a specific hypothesis about the relationship of a disease to an assumed cause by conducting a statistical analysis that relates the exposure of interest to the disease of interest→ cohort, case control

characteristics of environmental exposures

usually involuntary exposures to chemical, physical or biological contaminants from the general or occupational environment usually very low and often difficult to measure, often many of them in complex mixtures and correlated with each other, often exposure levels do not differ very much among individuals within areas, multiple routes of exposure, relative risks can be very low although exposed populations may be very large confounders, effect modifiers, and determinants of exposure status usually labels for exposures such as personal habits, nutritional status, genotype, socioeconomic factors, etc.

two ways to perform non-cancer risk assessment

1. estimate dose with exposure assessment and then compare to health based benchmark, dose response experiment -plot dose and adverse effect on graph, model response curve, getcurve model with LOAEL, NOAEL, and LD50 -benchmark→ Reference Dose 2. measure environmental concentration and then compare to standard REL (concentration benchmark, calculated for different time frames especially in air environment)→ divide dose with no effect in air by safety factors to get REL ***Difference: concentration of air at x vs. having a dose, different numbers cover different populations over different time frames

3 essential characteristics for descriptive Epi

1. time 2. person 3. place

how many approaches are there in a non-cancer risk assessment?

2

hazard quotient

Concentration (EF)/REL or reference dose, potential for adverse effects of concern when hazard quotient is higher than one, means exposure exceeds reference dose, adverse health effect possible HQ= Actual Exposure Dose/RfD HQ > 1 : Exposure exceeds reference dose, adverse health effects possible HQ <1: No adverse effects likely

descriptive/observational epidemiology

Disease in a population and observes the basic features of its distribution in terms of time, place, and person→ observational study, community health survey, cross sectional study, case series important to have solid foundation in descriptive epidemiology and exposure assessment before moving onto analytic epidemiology

non-cancer risk assessment approach 1

Estimate dose Compare dose to health-based benchmark (e.g., reference dose RfD) NOAEL, LOEL, LD50

non-cancer risk assessment approach 2

Measure environmental concentration Compare environmental measurement to standard (e.g., reference level Reference Exposure Level)

NSRL

No significant risk level exposure per day (intake rate) associated with acceptable cancer risk defined in California under Proposition 65 get acceptable exposure in a lifetime associated with certain risk/potency ( lifetime risk calculation essentially, derived from risk characterization formula), can add age specificity factor for those under 10→ check with ratio of exposure to see if over 1, means exposure exceeds 10^-5 risk set by prop 65

LOAEL vs. NOAEL

ONLY use the LOAEL when you don't know the NOAEL Why is UF= 10? → This came from EPA based on engineering research a number had to be put in place and 10 worked best. Allow a certain level of contaminant that won't let people become terribly sick.

environmental exposures and health risks in CA child care facilities case study

Performed environmental monitoring in CA child care facilities - air and dust samples collected from 40 childcare facilities. tested for: particles, pesticides, flame retardants, PFCs, phthalates, VOCs, carbonyl (Volatile organic carbon) around 40 VOCs quantified via mass spectral fingerprinting, many unknown peaks observed on chromatograms→ unmeasured pollutants present, 130 unknown found, vast majority without health based exposure benchmarks reviewed aggregate tex databases and applied QSAR models→ classification models used to predict toxicity based on similar chemicals Hazards score > 3 for siloxanes, fragrant related compounds, and terpenes compounds with demonstrated hazards→ VOCs exceeding benchmarks and flame retardants and phthalates exposure also exceeded cancer guidelines Limitations: many chemicals lack toxicity information, need to better characterize indoor contaminants esp in air, better tools to predict toxicology, efficacy of interventions to reduce known risks→ difficulties with risk assessment levels indoors of formaldehyde were the highest

reasons for increased importance of epidemiology

Reduction of infectious diseases increase in human lifespan increase in chronic diseases (the epidemiological transition) estimated 80-90% of cancers due to environmental factors understanding of cancer latency toxicology tests showing cancer danger in animals increase in analytical capability of chemists Silent Spring by Rachel Carson