TOXICOLOGY II

1
TOXICOLOGY II

• FROM DATA TO STANDARDS

2
Setting Drinking Water Standards

• The federal Safe Drinking Water Act requires the
  Environmental Protection Agency (EPA) to regulate
  drinking water to protect public health.

3
Setting Drinking Water Standards

• Acute poisoning is not a worry with drinking
  water.
• Standards are to protect people from chronic
  health effects.

4
Setting Drinking Water Standards

• EPA has a national standard for each drinking
  water contaminant. (80 so far)
• Called Maximum Contaminant Level

5
Setting Drinking Water Standards

• Maximum Contaminant Level is
• A Estimate of the Max. Concentration an average
  person could drink every day without health
  problems.
• Average adult (70 kg) male who drinks 2L of water
  a day for 70 years.

6
Setting Drinking Water Standards

• Maximum Contaminant Level is
• Developed for animal studies
• Lower standards are set if one group of humans
  are especially sensitive to a contaminant.
• Topic Drinking Water Standards
• Go to www.sciLINKS.org
• Code ATR04

7
Setting Drinking Water Standards Uncertainty
Factor

• Because animals NOT humans are used there is a
  lot of uncertainty.
• An Uncertainty Factor is used to correct for
  differences between experimental animals and
  humans.
• Uncertainty Factors range from 10 to 1000
• 10 is used if good data on humans is available,
  if not higher numbers are used.

8
Setting Drinking Water StandardsUncertainty
Factor

• Example
• 200mg/kg 100 2mg/kg
• safe dose uncertainty adjusted safe
  . in mice factor dose in humans
  

9
Questions Used in Converting Animal Data to Human
Drinking Water Standards I

• TOPIC Human Characteristics
• QUESTIONS
• How much does the average person weigh?
• How much water does the average person drink?
• How long does the average person live?

10
Questions Used in Converting Animal Data to Human
Drinking Water Standards II

• TOPIC Chemical Characteristics
• QUESTIONS
• How much of this chemical are humans exposed to
  through other sources?
• Is this chemical broken down quickly or does it
  build up in the human body?
• Is it suspected to cause cancer?

11
Questions Used in Converting Animal Data to Human
Drinking Water Standards II (Continued)

• Do males and females react differently to the
  chemical?
• Does a baby, elderly person or a person with a
  weakened immune system react differently than an
  average person?

12
Questions Used in Converting Animal Data to Human
Drinking Water Standards III

• TOPIC Data Characteristics
• QUESTIONS
• What uncertainty factors should be used when
  switching between the chemicals effects in
  animals and its estimated effects in humans?

13
FROM DATA TO STANDARDS

• EXAMPLE Say 200mg/kg/day of compound A is the
  highest dose that causes no chronic health
  problems in rats.

14
FROM DATA TO STANDARDS STEP 1

• Apply the right Uncertainty Factor.
• For example use 100 if we have good data.
• 200mg/kg 100 2mg/kg
• safe dose uncertainty adjusted safe
  . in mice factor dose in
  humans

15
FROM DATA TO STANDARDS STEP 2

• Convert the number into the amount for humans
  instead of rats. EPA uses 70 kg as avg. weight
  of humans.
• 2mg/kg/day 70kg 140 mg/day .adjusted
  weight of comparable dose
  safe dose avg. human in
  humans .
  Male adult

16
FROM DATA TO STANDARDS STEP 3

• Ask if all of this 140 mg/day were consumed in
  drinking water what would the concentration be?
  EPA uses 2L of water/day.
• 140 mg/day 2 L/day 70mg/L

17
FROM DATA TO STANDARDS STEP 4

• We get contaminants from lots of places besides
  water, so EPA figures only 20 of any daily
  consumption of a compound comes from water.
• 70 mg/L 0.20 14mg/L

18
From Data to Standards

• Carcinogens the Maximum Contaminant Level is the
  lowest concentration that is measurable.
• Remember Nothing is absolutely safe