toxicology update - faculty support sitefaculty.ucr.edu/~krieger/ventura2008presentation.pdf ·...
TRANSCRIPT
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Toxicology UpdateBob Krieger, Ph.D. Cooperative Extension Specialist
&Toxicologist Department of EntomologyUniversity of California, Riversidehttp://faculty.ucr.edu/~krieger/
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PesticidesPesticidesVery special chemicals!Very special chemicals!
Preserve safe uses!
You make a difference–know your stuff!
[email protected]@ucr.edu, Personal Chemical Exposure Program, 2008, Personal Chemical Exposure Program, 2008
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We live in a chemical world!We live in a chemical world!More than 32,000,000 known
• OriginNatural and Synthetic
• ClassOrganic and Inorganic
• UseProcess •• Commercial Products •• Pollutants
Foods • Drugs • Cosmetics • Pesticides
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LethalLethal
%
← DOSE →
ActiveActive
or or
““SideSide--EffectEffect””
Safety Evaluation: Exposure-Response Relationships
LD50ED50LOAEL
“Threshold”
Commercial ChemicalsDrugs
Pesticides
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None
50%->
100%
Dose (Exposure)
“Dose-Response Curve”
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“…for seven years of misfortune,I had one moment of good luck!”
Chemotherapy: Drug Safety
1909 “606” Salvarsan
A Magic Bullet
An arsenic drug used to treat syphilis prior to use of penicillin
Therapeutic Index
Lethal dose/Effective dose
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LethalLethal
% Responding
← DOSE →
ActiveActive
or or
““SideSide--EffectEffect””
Safety Evaluation: Exposure-Response Relationships
LD50ED50
Paxil LD50 500 mg/kg
Nausea, insomnia, fatigue 20 mg/person
Therapeutic Index >10,000
Margin of safety ≈1
#1 Antidepressant
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LethalLethal
%
← DOSE →
ActiveActive
or or
““SideSide--EffectEffect””
Safety Evaluation: Exposure-Response Relationships
LD50ED50
Acetamenophen LD50 1944 mg/kg
Liver toxicity 50-60 mg/kg
Pain relief (2 x 325 mg) 1 mg/kg
TI ≈ 2000
MOS ≈ 50
OTC Pain reliever
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LethalLethal
%
← DOSE →
ActiveActive
or or
““SideSide--EffectEffect””
Safety Evaluation: Exposure-Response Relationships
LD50ED50LOAEL
“Threshold”
Commercial ChemicalsDrugs
Pesticides
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RfD “No Effect”NOAEL
LethalLethal
%
← DOSE →
ActiveActive
or or
““SideSide--EffectEffect””
Safety Evaluation: Exposure-Response Relationships
LD50ED50LOAEL
P E S T
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Productc Formulation Active Ingredient.
Rat oralLD50
(mg/kg bw)
Human product
equivalents of LD50
Termidor 0.06% fipronil 97 16 L
Talstar 0.06% bifenthrin 54 (f) 9 L
Gourmet 1% borate 2500 25 kg
Vitis 0.001% imidacloprid 450 4,500 L
LD50s aren’t about risk—safety evaluation is about exposure and use!
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Active Ingredient. Rat, oralLD50
(mg/kg bw)
LowObserved Adverse
Effect Level
(mg/kg-d)
NoObserved Adverse
Effect Level
(mg/kg-d)
Reference Dose
Includes “Uncertainty
Factors”(chronic)
fipronil 97 7 2.5 0.025neuro
bifenthrin 54 (f) 2 1 0.015neuro
boron 2500-5000 5chronic
2.5boron
Dietarybackground
imidacloprid 450 55 5.5 0.057
Margin of exposure = NOAEL / 100 or more
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LethalLethal
%
← DOSE →
ActiveActive
or or
““SideSide--EffectEffect””
Safety Evaluation: Exposure-Response Relationships
LD50ED50LOAEL
“Threshold”
Commercial ChemicalsDrugs
Pesticides
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Leading Causes of Death U. S. A., 2004
All causes 2,443,000
Heart disease 697,000
Cancer 557,000
Stroke 163,000
Chronic lung disease 125,000
Unintentional injuries 107,000Diabetes 73,000
Flu 66,000
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Deaths, 2004 Total Rate/million
All unintentional injuries 111,000 378Motor vehicle accidents 46,200 157Falls 20,200 69Poisoning 13,300 45Choking 4,900 17Fires and smoke 3,900 13Drowning 3,800 13Suffocation 1,300 4Heat or cold 1,200 4
All others 16,200 55
Accidental U. S. Deaths, National Safety Council, 2005-2006
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All U. S. Deaths Due to Injury
Death x 1000
Year 2002 2001 2000Transportation 107 102 98Non-transportation 58 54 51Venomous animals and plants 0.076 0.061 0.080Poisoning 18 14 13Pesticide (0.007; 2002)
Suicide 32 31 29Undetermined intent
(poisoning)3 3 3
Medicine and surgery 3 3 3
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Normal Occupational
%
What about everyday exposures and safety evaluation?
← DOSE →
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Unintended Pesticide Exposures
• Common (residues from use) – Agricultural “Integrated Pest Management”– Residential “Pest Control”
• Short term (min, hr, d, wks to yrs)• Responses: No Observed Adverse Effects• Regulations minimize continuing, low level
pesticide contacts
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RfD“No
Effect”Effective
Accidents
Normal
Occupational
Yes, Exposure goes with use!
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What is your concern?
Check ‘em out!LetterheadOne issue—keep it simple!First person, singular
“I….”
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NOTICE OF PROPOSED REGULATORY ACTION
“What the new regulatory action will do!”
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FORM OF COMMENTS
Public hearing if any interested person submits a written request to DPR no later than 15 days prior to the close of the written comment period.
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EFFECT ON SMALL BUSINESS
“DPR has determined that the proposed regulatory action does affect small businesses.”
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AGENCY CONTACT
Send written comments to:
Regulations Coordinator
Office of Legislation and Regulations
Department of Pesticide Regulation
1001 I Street, P. O. Box 4015
Sacramento, CA 95812-4015
916-445-3991
Keep a copy!
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Note: If unavailable, questions may be directed to the following person
For example,
Environmental Program Manager
Worker Health and Safety Branch
916-445-4163
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Notice of Proposed Action, the Initial Statement of
Reasons, and the proposed text of the regulation
are also available on DPR’s Internet Home Page
http://www.cdpr.ca.gov
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Accessing “Writing a Letter”
http://faculty.ucr.edu/~krieger/
click PCEP View