PH150B study guide

Paracelsus

"founder of Toxicology" the dose makes the poison aka too much of anything is bad

Modifying factor (i.e no info for children) - scale of 1-10

(i.e no info for children) - scale of 1-10

how to properly risk communicate

-accept and involve public -listen to audience -be truthful, honest -coordinate with other sources -meet media needs -speak clearly, compassionately -prepare, plan carefully, evaluate communication performance

Silent Spring - Rachel Carson

-argued that most cancer caused by environmental exposures -influential in movement against pesticides

VOC's found in child care centers that may exceed CA cancer guildelines

-benzene -choloform -ethylbenzene -acetaldehyde -formaldehyde -napthalene

Bradman child care facility study: research needs

-characteristics of indoor contaminants -tox info on identified contaminants -tools to predict toxicology -efficacy of risk interventions

Time frame of exposure assessment

-current -post-hoc (after the fact) -a priori (before)

limitations of animal toxicology studies

-different species -inevitably different relative exposures -no accounting for differing human experiences -no accounting for inerxns between chemicals

Comoponents of Risk Assessment (according to Nat'l Research Council Risk Paradigm

-hazard identification exposure -exposure assessment -dose-response relationship ===> risk characterization

Proposition 65

-identifies chemicals as having been to cause cancer, reproductive harm by authoritative bodies or by state/federal agency -those that have been identified by CA are thus identified the world over; companies try not to have chemicals on this list

biological monitoring

-levels of chemicals/their products in biological samples -biomarkers of exposure may be targeted

Definitions of Risk

-probability of injury, disease, or death from exposure to a chem agent or a mix =probability* magnitude =hazard + outrage

why is risk communication important?

-public health interest -demand for public info based on concerns from past -right to know laws -attempt by gov't and industry to lower risk controversies -awareness that public response to risk can be amplified/attenuated by manipulators

tools of exposure assessment

-questionnaires -record review -environmental measurements -personal monitoring -modeling -geospatial assessment -biomonitoring -biologically-based exposure

importance of environmental epidemiology

-reduction in infectious disease -increase in human life span -increase in chronic diseases -understanding of cancer latency -increase in analytical capability of chemists

Factors that influence toxicity:

-route of entry -duration of exposure -interactions b/w multiple chemicals -individual activity/susceptibility

Bradman child care facility study: chemicals with highest hazard score

-siloxanes -fragrance related compounds -terpenes

Association is only causality if research shows:

-strength -consistency -specificity -temporality -biological gradient (dose/response) -plausibility -coherence

how to investigate toxicity

-study animals: experiential studies -tissue culture -epidemiology -clinical trials

Ch. 6: Risk Communication

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Chapter 3: Exposure Assessment

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ch. 7: lead

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chapter 4: environmental epidemiology

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Chapter 5: Risk Assessment

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second approach to non-cancer Risk-Assessment

1. environmental concentration 2. Compare environmental measurement to concentration benchmark

Non-cancer risk assessment

1. estimate dose 2. compare dose to health-related benchmark (RfD)

Purposes of Epidemiology

1. identify causes, risk factors of disease 2. Determine the extent of disease in the community 3. Study natural history, prognosis of disease 4. evaluate preventative, therapeutic or intervention measures 5. provide data/foundation for public policy

antagonism

2 chemicals interfere with each others actions, or one interferes with action of the other

Epidemiologic Transition

Life span changes from due to infectious disease to chronic disease

John Snow

London water supply and cholera death - outbreak because of Broad Street pump

Prop 65: MADL

Maximum Adverse Dose Level (i.e. reproductive risk) =NOAEL/1000 because exposure affects fetuses much more intensely

Prop 65: NSRL

No Significant Risk Level (i.e. cancer) =risk/potency measure of exposure of chemical per day associated with acceptable cancer risk

Odds Ratio interpretation

OR=1: risk is same in exposed, unexposed OR>1: risk is higher in exposed than in unexposed OR<1: risk is lower in exposed than in unexposed (agent protective)

OSHA

Occupational Health and Safety Administration - measures workplace exposures

Odds ratio vs. Risk Ratio

Odds ratio calculates odds - p/(1-p) risk ratio calculates probability - p/(all possible outcomes)

Public Information vs. Risk Communication

Public Information may not align w risk communication - may be biased towards industry instead of safety

REL

Reference Exposure Level can be acute, 8 hour, chronic, or EPA reference concentration

Rachel Carson

Silent Spring - pesticide awareness

disease cluster study

a group of similar diseases

adduct

a stable covalent bond b/w a toxicant and a biological receptor

acute v subacute

acute: single exposure, >24 hrs subacute: exposed >1 month

clinical trials

administration of chemicals to humans using careful clinical observations, lab measurements

factors that influence toxicity:

age, sec, race, health status, exercise, genetic makeup, previous exposure history

Dose

amount of a chemical/agent that comes into contact with organism

Dose Effect Curve

an individual dose-response curve, measuring individual response intensity

common error in epidemiology

attempting analytic epi without having good enough exposure assessment or descriptive epi

calculating RfD (concept)

benchmark factor (or LOAEL/NOAEL) divided by uncertainty factor and modifying factor

example of linear dose-response

cancer

randomized control trial

clinical trials, control for confounders

examples of analytic epidemiology study design

cohort, case control study, randomized control trial

case series study design

collection of cases, may be subject to selection bias

additive effects of chemical mixtures:

combined effect equal to the sum of individual effects

synergistic effect of chemical mixtures

combined effect is greater than sum - multiplied? ex: smoking + asbestos ==> cancer

examples of descriptive epidemiology study design

community health survey, cross sectional study, case series

case-control study

compare ppl with disease and without disease

risk characterization

comparison of exposure to health-based benchmarks (aka toxicity assessment)

exposure equation (simplified)

concentration, intake rate, exposure factor; divided by body weight

types of modeling

conceptual model, models of concentration across space

Exposure

contact between a chemical and a person/organ

retrospective cohort study

defines incidence in an existing group

Hazard identification

determining whether or not a chemical poses a hazard discerned from extensive lit review

descriptive epidemiology

distribution of disease in a population, observing basic features of its distribution

what does an industrial hygienist do?

ensure and assess safety of workplace

the exposome

environmental exposures of populations through a lifetime

Reference Dose (RfD)

estimate of the daily acute/chronic exposure that is likely to be without risk of adverse effects

effect modification

exposure has different affect among subgroups - associated with outcome, not exposure ex: gender as an effect modifier of breast cancer

Hazard Quotient

exposure/RfD HQ>1 ==> adverse health effects

exogenous exposure

external - air, water, diet, skin

Confounding

factor associated with both exposure and outcome but doesn't lie within causal pathway. ex: SES stressors as confounder of IQ of Salinas children as well as pesticide exposure

Mathieu Orfila

foundation of forensic toxicology - Arsenic

exposure factor

frequency and duration of exposure divided by time length

ecological study:

group exposure & group prevalence - establishes hypothesis

NOAEL

highest non-zero dose that no effect is observed

Sources of lead exposure

house paints, gasoline, drinking water (by way of plumbing) ==>all have been banned

route(s) of exposure affecting liver

ingestion

route(s) of exposure affection circulatory system

inhalation, dermal contact

endogenous exposure

internal - hormones, gut flora, etc.

environmental exposure + characteristics

involuntary exposure to contaminants from ambient/occupational environment -low levels, in complex chemical mixtures, multiple exposure routes, do not differ much b/w individuals

lead in occupational settings

lead smelting/mining construction automobile repair plumbing police/military

LOAEL

lowest dose that an effect is observed

EPA

measures chemicals in ambient air and water

Dose units

mg/(kg*day)

Uncertainty Factors (4)

multiples of 10: -if interspecies -if variability within human population -if using less than chronic data -if using LOAEL instead of NOAEL

What level of lead is acceptable in the blood?

none!

Alice Hamilton

occupational, environmental health; addressed lead and other hazards

epidemiology studies

populations exposed in the normal course of life, or occupational/accidental exposure

forms of exposure measure; which one is ideal

quantitative estimation (preferred) or classification

cross-sectional study

snapshot in time - prevalence vs. exposure

lead in commercial products

still used in bridge paint, computers, pewter, ceramic glazes, jewlery, car batteries. x-ray shields, pdts. from other countries

subchronic vs. chronic

subchronic: exposed 1-3 mo. Chronic: exposed <3 months

analytic epidemiology

tests for a specific hypothesis abt the relationship of the disease to an assumed cause - statistical analysis that relates exposure of interest to disease of interest

toxicology

the study of the adverse physiologic effects of chemical, physical or biological agents on living organisms. includes prevention and treatment of these effects

types of Dose Response Curves (3)

threshold response u shaped curve optimal dose response

triad of descriptive epidemiology

time, person, place

Risk Assessment

to characterize the likelihood or harm to assist decision makers acting to tolerate, mitigate, or eliminate the environmental harm

How is hazard established?

top-down model: linking disease to cause bottom-up: linking chemicals to disease (toxicological harm)

toxins

toxic substances produced by living organisms

toxicants

toxic substances that are man made of result from human activity

common exposure biomarkers

urine, blood, breast milk, saliva, hair

potentiation

when a non-toxic chemical causes another chemical to become more toxic