2015 uemx 3613 topic4-risk assessment (1)

7/24/2019 2015 UEMX 3613 Topic4-Risk Assessment (1)

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ENVIRONMENTAL RISK ASSESSMENT

Hazard identification

Dose-response assessmentHuman exposure assessment

Risk characterization


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Risk Hazardimplies capability of substance to cause an adverse

effect

Riskis a measure of the probabilitythat the hazard will occur

under specific exposure conditons.

Some risk are well defined (eg. frequency and severity of

automobile accidents)

In contrast, other hazardous activities such as thoseresulting from the use of alcohol and tobacco are more

difficult to document. Their assessment requires complex

epidemiological studies.


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Risk assessment

Risk assessmentis the scientific approaches to collect

data that are used to relate the response to a dose of a

pollutant. Such dose-response data can be combined toestimate overall risk assessment.

Risk managementis the process of deciding what to do

and how to allocate national resources to protect publichealth and the environment.

Risk is being expressed as a percentage or as a decimal

fraction, no units.

Example:

In the U.S in 2001, there were about 3.9 million deaths per year. Of these,

about 541,532 were cancer-related.

The risk of dying from cancer in a lifetime was about 0.14 or 14%.

The annual risk (assuming a 70-year life expectancy) is 0.002 or 0.2%


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One of the objectives

of RA is to provide astarting point in

balancing the

tradeoffs between an

acceptable

incremental risk and

the cost of controlling

risk to that level.RA is divided into 4

steps:


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Terminology:

Exposureand doseare often used interchangeably.

Strictly, exposurerefers to either a deliberate or non-

deliberate non-quantifiable situation, whereas doserefers

to the quantity of toxicant administered to, or ingested by

an organism.

Threshold- the point that must be exceeded to begin

producing a given effect or result or to elicit a response


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Terminology:

Acute toxicitya measure of the amount of a

substance that is needed to cause some acute

response, such as organ injury, coma, or even

death. The effect can be within a short period or

after a single exposure;

At the prolonged exposure a chronic toxicityis

observed.


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mutagen an agent that induces a permanent

change in the genetic material of the cellexposed to it, which can be transmitted to future

generations

carcinogen an agent that causes a cancer cancer collective noun for 200 different

diseases, all of which are characterized by

unrestrained cell divisions.

teratogen an agent that inducesabnormalities in an embryo/fetus when

administered to the maternal organism

Terminology:


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1. Hazard identification: What are we considering?

(LD50; mutagenesis; carcinogenesis; animal tests;human studies)

Determine whether or not a particular chemical is

causally link to particular health effect, such as cancer or

birth defects


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Experimental design:

There are a variety of parameters which have to be considered

when testing the toxicity of a substance, assuming that it ispure.

-choice of animal model

-route of administration

- physical state of toxicant (gas, liquid, lipophilicity, etc)

- dose and duration of treatment: acute/sub-acute or chronictoxicity testing


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Toxicity testing in animal

Three types of animal tests:

i.Short-term test, called the Ames mutagenicity assay, subjects

special tester strains of bacteria to the certain chemical.

ii.Intermediate testing involve relatively short term (several

months duration) carcinogenesis bioassays in which specificorgans in mice and rats are subjected to known mutagens to

determine whether tumors develop.

iii.The most costly, complex and long-lasting testchronic

carcinogenesis bioassay.- Two species of rodents must be tested (mice and rats)

- At least 50 males and 50 females of each species for

each dose

- At least two doses must be administered (plus a no-

dose control)


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Human studies

Epidemiologic is the study of the incidence rate of disease in

real populations.

Preliminary data analysis involves setting up a simple 2 x 2

matrix.


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Epidemiologic Data Analysis

Suppose 5 percent of individuals exposed to a chemicalget a tumor, and 2 percent of those not exposed get the

same kind of tumor. Find the relative risk, attributable

risk, and odds ratio.

Relative risk = 2.5

Attributable risk = 0.03

Odds ratio = 2.58

The relative risk and the odds ratio both are above 1.0, so they

suggest a relationship between exposure and tumor risk. For those

who were exposed, the risk of tumor has increased by 0.03 over who

were not exposed.


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Suppose 30 out of 500 rats exposed to a potential

carcinogen develop tumors. A control group of 300 rats

not exposed to the carcinogen develops only 10 tumors.

Find the relative risk, attributable risk, and odds

ratio. Do these indicators suggest that there might be a

relationship between exposure and tumor risk?

Relative risk = 1.8

Attributable risk = 0.0267

Odds ratio = 1.82

The relative risk and the odds ratio both are above 1.0, so theysuggest a relationship between exposure and risk. For the rats were

exposed, the risk of cancer has increased by 0.0267 over who were

not exposed. All three measures indicate the relationship between

exposure and tumor risk.


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Limitation of Animal studies and Human studies

Animal studies Human studies

- No species provides an exactduplicate of human response.

Certain effects that occur in

common lab animals generally

occur in people. The exceptions

are toxicities dependent on

immunogenic mechanisms. Mostsensitization reaction are difficult

to induce in lab animals.

- Inability of a bioassay to detect

small risks. Regulatory try to

restrict human risks due toexposure to carcinogens to level

of about 10-6, yet animal studies

are only capable of detecting

risks down to 0.01 to 0.1.

- Large populations are required todetect a low frequency of

occurrence of a toxicological

effect.

- A long or highly variable latency

period may be needed betweenthe exposure to the toxicant and

a measurable effect.

- Competing causes of the

observed toxicological response

make it difficult to attribute adirect cause and effect. (cigarette

smoking, the use of alcohol and

drugs, prior disease states)


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Dose-response mortality curves for acute toxicity.

LD50= Lethal Dose for 50% of a tested group


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2. Dose-response assessment: How bad it is?

(threshold dose; dose-response curve; chronic daily

intake, reference dose, hazard quotient, hazard index)

To obtain a mathematical relationship between the

amount of a toxicant that a human is exposed to and the

riskthat will be an unhealthy response to that dose.

The dose of an exposure averaged over an entire

lifetime (for human it is assumed to be 70 years)


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Hypothetical dose-response curves. Dose-response

curves for carcinogens are assumed to have no

threshold; that is, any exposure produces some

chance of causing cancer.


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The potency factor is the slope of the dose-

response curve.

Incremental lifetime cancer risk= CDI x PF


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Chronic Daily Intake:

(how much is consumed every day)

)_(_

)/_(__)/(

kgweightBody

daymgdosedailyAveragedaykgmgCDI

)/(365__)/(70__)(_

)/(__)/(___)/(

yrdaysxlifeyrsxkgweightBody

lifedaysExposurexdayLrateIntakexLmgionConcentratCDI

)/(365__)/(70__)(_

)/(__)/(___)/( 33

yrdaysxlifeyrsxkgweightBody

lifedaysExposurexdaymrateIntakexmmgionConcentratCDI

For contaminants in water:

For contaminants in air:

When a risk assessment is made for exposures that do not last the entire lifetime:


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If 70 kg people breath 20 m3/day of air containing 10-3

mg/m3of carcinogenic VOC throughout their entire 70year lifetime, find the cancer risk. Given the potency

factor = 0.01 (mg/kg-day)-1.

CDI = 0.000285 mg/kg-day

Risk = CDI x PF = 2.9 x 10-6


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The drinking water standard for tetrachloroethylene is 0.005 mg/L.

Suppose a 70 kg person drinks 2 L of water every day for 70

years. Find the cancer risk for this individual. Potency factor of

tetrachloroethylene is 5.1 x 10-2(mg/kg-day)-1.

If a city with 500,000 people in it also drinks the same amount of

this water, how many extra cancers per year would be expected?

Assume the standard 70 year lifetime.

CDI = Average daily dose (mg/day) / body weight (kg)

= 1.43 x 10-4mg/kg-day

Incremental lifetime cancer risk = CDI x PF = 7.3 x 10-6

So, over a 70-year period, the upper-bound estimate of the probability that

a person will get cancer from this drinking water is about 7 in 1 million.

If there are 7.3 cancers per million people over a 70-year period, then in

any given year in a population of 500,000, the number of cancers

caused by TCE would be 0.052 cancers/year.


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The drinking water standard for tetrachloroethylene is

0.005 mg/L. Using the EPA exposure factors forresidential consumption (Daily intake = 2L for adult,

exposure frequency = 350 days/year, exposure

duration = 30 years, body weight = 70kg for adult),

what lifetime risk would this pose?

Lifetime risk = CDI x Potency factor

= 3.0 x 10-6


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Mainstream smoke inhaled by a 70 kg smoker contains

roughly 0.03 mg per cigarette of the class B2

carcinogen, benzo(a)pyrene. From an individual whosmokes 20 cigarettes per day for 40 years, estimate

the lifetime risk of cancer caused by that

benzo(a)pyrene (there are other carcinogens in

cigarettes as well). Given that potency factor

(inhalation route) of benzo(a)pyrene is 6.11 (mg/kg-day)-1.

CDI = 0.0049 mg/kg-day

Risk = CDI x PF = 0.03


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The reference dose for noncarcinogenic effects:

Noncarcinogens - there is an exposure threshold; that is,

any exposure less than the threshold would be expected toshow no increase in adverse effect.

Lowest-observed-effect level (LOEL) : the lowest dose

administered that results in a response

No-observed-effect level (NOEL) : the highest dose

administered that does not create a response

Reference dose (RfD) or acceptable daily intake (ADI)anindication of a level of human exposure that is likely to be

without appreciable risk (unit : mg/kg-day averaged over a

lifetime)


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RfD is obtained by dividing the NOAEL by an appropriate uncertainty

factor. The uncertainty factor is typically between 10 and 1 000.

Reference

Dose

No-Observed-

Adverse-

Effect Levels

Lowest-Observed-

Adverse-Effect

Levels


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Comparison between actual exposure and RfD to see

whether the actual dose is supposedly safe.

(mg/kg-day)

For non-carcinogens, the daily dose is averaged only over the

period of exposure.

If hazard quotient < 1.0, there should be no significant risk of

toxicity.

If hazard quotient > 1.0 could represent a potential risk.

When exposure involves more than one chemical:

Hazard index = sum of the hazard quotients


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Suppose a 50 kg individual drinks 1 L/day of water

containing 2 mg/L of 1,1,1-trichloroethane, 0.04 mg/L of

tetrachloroethylene, and 0.1 mg/L of 1,1-dichloroethylene. Given the oral RfD for 1,1,1-

trichloroethane = 0.035, tetrachloroethylene = 0.010,

1,1-dichloroethylene = 0.009. What is the hazard index?

HQ (1,1,1-trichloroethane) = 1.14

HQ (tetrachloroethylene) = 0.08

HQ (1,1-dichloroethylene) = 0.22

Hazard index = 1.44


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3. Exposure assessment: How much of it?

Determine the size and nature of the population that has been

exposed to the toxicant under consideration and the length of

time and toxicant concentration to which they have been

exposed.

Firstly, the toxicants should be transported from the source to

the point of contact with human (pathways), and secondly, aprobability of toxicants contact with human should be

estimated (amount of contact).


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Analyze the exposure pathway

Estimate the concentration of toxicants

at a particular exposure point

Human intake estimates (based on a

lifetime of exposure)duration of

exposure, amount of contaminants into

each exposed persons body, number of

people exposed


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Bioco ncentrat ion factor (BCF, L/kg) : Amount of

consumption of a product containing toxicants by a human.

For example: BCF provides the key link measuring the

tendency for a substance to accumulate in fish tissue.

Concentration of toxicant in fish (mg/kg) = concentration in

water (mg/L) x bioconcentration factor (L/kg)

Another way is the estimation of half-l i fe(days) of various

contaminants in water, air, and soil (contaminant

degradation rate).

Half life is the time required for the concentration to be

reduced by 50%.

t1/2 = ln 2 / k C(t) = C0e-kt


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Bioconcentration of TCE

Given a daily intake of 54 g of fish for a person, 350 days per year for

30 years eating locally caught fish, estimate the lifetime cancer riskfrom fish taken from waters containing a concentration of

trichloroethylene (TCE) equal to 100 ppb (0.1 mg/L). The

bioconcentration factor for TCE is given as 10.6 L/kg. The cancer

potency factor for an oral dose of TCE is 1.1 x 10-2(mg/kg-day)-1.

TCE concentration in fish = 1.06 mg TCE/kg fish

CDI = 3.36 x 10-4mg/kg-day

Incremental lifetime risk of cancer = CDI x PF = 3.6 x 10-6


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Suppose an underground storage tank has been leaking for many

years, contaminating the groundwater and causing a contaminant

concentration directly beneath the site of 0.30 mg/L. The

contamination is flowing at the rate of 0.5 ft per day toward a publicdrinking water well 1 mile away (1 mile = 5280 ft). The half-life of the

contaminant is 10 years.

a.Estimate the steady-state pollutant concentration expected at the

well.

b.If the potency factor for the contaminant is 0.02 (mg/kg-day)-1,

estimate the cancer risk if a 70 kg person drank 2 L of this water per

day for 10 years.

Time required to travel to the well = 10560 daysThe pollutants is assumed degrade exponentially, so the reaction rate

coefficient k = 1.9 x 10-4/day

Pollutant concentration in well = 0.040 mg/L

CDI = 1.6 x 10-4mg/kg-day

Lifetime cancer risk = CDI x PF = 3.2 x 10-6


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4. Risk characterization : So, what is the risk?

involves analysis of gathered data to be used in decision-

making process to set regulatory requirements and control

measures.

It is the final stage in the risk assessment process and involvesthe prediction of the frequency and severity of effects in

exposed populations.

All data collected from exposure and toxicity assessment are

reviewed to corroborate qualitative and quantitative

conclusions about risk.


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Since most risk assessments include major uncertainties, it is

important that biological and statistical uncertainties are described in

the risk characterization.

In some complex risk assessments such as for hazardous waste sites,

the risk characterization must consider multiple chemical exposures

and multiple exposure pathways.

Simultaneous exposures to several chemicals, each at a

subthreshold level, can often cause adverse effects by simple

summation of injuries.

Individuals are often exposed to substances by more than one

exposure pathway (e.g. drinking of contaminated water, inhaling

contaminated dust). In such situations, the total exposure will

usually equal the sum of the exposure by all pathways.


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Estimate the lifetime average chronic daily intake of benzene from

exposure to a city water supply that contains a benzene concentration

equal to the drinking water standard. The allowable drinking water

concentration (maximum contaminant level, MCL) is 0.005 mg.L-1.

Assume the exposed individual is an adult male (78kg) who consumeswater at the adult rate (2.3 L/day) for 63 years, that he is an avid

swimmer and swims in a local pool (supplied with city water) 3 days a

week for 30 minutes from the age of 30 until he is 75 years old.

(Assume a total lifetime of 75 years.) As an adult, he takes a long (30

minutes) shower every day for 63 years. Assume that the average air

concentration of benzene during shower is 5g.m-3. From the

literature, it is estimated that the dermal uptake from water is 0.0020

m3.m-2.h-1. Surface area available for an adult male is 1.94 m2.Direct

thermal absorption during showering is no more than 1% of the

available benzene because most of the water does not stay in contact

with skin long enough. Amount of air breathes daily for adult male is0.633 m3/hr and water swallowing rate while swimming is 50 ml/hr.

Estimate the riskfrom exposure to drinking water containing the MCL

for benzene. (Given potency factor of benzene for oral route = 0.015

(mg/kg-day)-1 and inhalation route = 0.029 (mg/kg-day)-1)


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Five routes of exposure:

1. Ingestion

2. Dermal contact while showering

3. Dermal contact while swimming4. Inhalation of vapor while showering

5. Ingestion while swimming

1. CDI = [(0.005 mg/L)(2.3 L/day) (365 days/year)(63 yrs)]/ [(78 kg)

(75yrs)(365 days/yr)] = 1.24 x 10-4mg/kg-day

2. Absorbed dose (AD) = [(0.005 mg/L)(1.94 m2)(0.002 m3/m2-h)

(0.5h/event)(1event/day)(365days/yr)(63yrs)(103L/m3)]/[(78kg)(75yrs)

(365days/yr)] = (1.04 x 10-4mg/kg-day

Given that direct dermal absorption during showering is no more that 1%

(because limited contact time)Actual dose of dermal contact, AD = (0.01) (1.04 x 10-4mg/kg-day) =

1.04 x 10-6mg/kg-day

3. AD = 3.19 x 10-5mg/kg-day

4. CDI = 1.70 x 10-5mg/kg-day

5. CDI = 4.11 x 10-7mg/kg-day


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Total exposure, CDIT= 1.74 x 10-4mg/kg-day

Drinking the water dominated the intake of benzene.

There are different slope factors for both oral and inhalation

routes. Because we do not have a slope factor for dermal

contact, we assumed that it is same as oral ingestion.

Risk = 2.85 x 10-6mg

This is the total lifetime risk (75 years) for benzene in drinking

water.

2015 uemx 3613 topic4-risk assessment (1)

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