HZ_Chlorpyrifosx - Toxipedia

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28 Οκτ 2013 (πριν από 3 χρόνια και 5 μήνες)

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Chlorpyrifos

ENV H 572

Hilary Zetlen

Chlorpyrifos


Organophosphate pesticide


Marketed by Dow Chemical
since 1965


Domestic and agricultural uses

Prevalent Use


Broad spectrum of applications


Treatment of crops, lawns, building materials.


10 million lbs. applied each year


Majority applied to corn (approx. 5.5 millions lbs. annually)


Commonly used for vegetables, tree fruit in Washington state


Home use canceled in 2000


Previously most commonly used residential pesticide


Limited to tightly controlled childproof mechanisms


Annual use, Lbs.

(% crop treated)

Regulatory Standing


CERCLA


Reportable quantity of release = 1 lb.


Clean Water Act


Allowable level = 20
ug
/ L


FDA


0.05
-
15
ppm

on food


FIFRA / EPA


Currently undergoing registration review


NRDC / PAN requesting revocation of registration


Final decision in 2015


Stakeholders


Dow Chemical Corp. and pesticide manufacturers


Agribusiness, small farmers, and agricultural communities


Consumers


Government agencies


The environment

Hazard Identification

What is it?


White crystalline solid


Synthesized from 3
-
methylpyridine


Hydrophobic; often applied
dry or in an oil/solvent
suspension


Frequently marketed as
Dursban/Lorsban


Organophosphate Pesticides


“Nerve agents”


Somewhat chemically similar to
sarin
, VX


Compounds of special concern to the EPA


Priority for review under Food Quality Protection Act


Cholinesterase inhibitors


Inhibits breakdown of acetylcholine


Major consequences throughout nervous system


Cognitive effects, among others




Acetylcholinesterase

Inhibition

Chlorpyrifos

Toxicity


Acute exposure


Numbness, headache, dizziness, nausea, difficulty breathing, loss of
consciousness, convulsions, paralysis


Chronic exposure


Cognitive impairment, disorientation, depression, lack of
coordination, speech difficulties


Other effects


Lack of evidence for carcinogenic effect


Possible endocrine disruptor!

Developmental Effects


Prenatal exposure


Significant growth deficits in length and
birthweight
, increase in birth
defects


Neurotoxicity


Disruption of brain development at sub
-
acetylcholinesterase

inhibiting
levels


Early childhood effects


Measured umbilical cord blood concentrations at delivery



>6.17 pg/
g

“high exposure” group


Associated with significant psychomotor and cognitive delays at 36
months


Dose
-
Response Assessment

Child ingestion in an agricultural setting

EPA Reference Dose


RfD

= 0.003 mg/kg/day


Dow Chemical Company:


Sixteen human male volunteers ingested 0, 0.014, 0.03, or 0.10 mg/kg/day of
chlorpyrifos



20 days at the low and mid dose; treatment of the high
-
dose group (0.1
mg/kg/day) discontinued after 9 days due to a runny nose and blurred vision in
one individual


Mean plasma
ChE

in this group was inhibited by about 65%


UF = 10 for human variability


FQPA, 1996: additional UF of 10 for children and females <50 years old


“Low
-
to
-
mid confidence” in estimated
RfD


IRED Human Health Assessment

Prenatal
chlorpyrifos

exposure


Average
birthweight

in “high exposure” cohort = 3.24 kg


Lowest observed umbilical plasma concentration = 6.17 pg/
g


Average adult plasma volume = 3.0 L



3.0 L * (1.025 kg/L) / 70 kg = 42
g

plasma/ kg body weight


42
g
/kg * 3.24 kg = 136.22
g

plasma/infant


(6.17 pg
chlorpyrifos
/
g

plasma) * 136.22
g

plasma = 840.48 pg/infant


So how many mg/kg?


840.48 pg/infant * (1 mg/1,000,000,000 pg) * (1 infant/3.24 kg) =



2.59 * 10
-
7
mg/kg at birth!!


about 100 times smaller than EPA
RfD




significant psychomotor and cognitive delays at 36 months



Exposure Assessment

Exposure Routes


Ingestion


Considered primary risk for
Chlorpyrifos

exposure for general
population


Metabolites present in urine in 82% of US adults


Inhalation


Requires presence of aerosolized pesticides


Particular risk for applicators, mixer
-
loaders


Dermal


Occupational exposures


“Take
-
home” exposures



Agricultural workers and their families


Much higher concentrations of
chlorpyrifos

in home


Correlates with proximity to
orchards/application zones


Accumulates on household
surfaces, dust, dirt


Lingers after application

Chemical fate


Biological half
-
life


Approx. 10
-
30 hours


Metabolites excreted in urine



Soil half
-
life


60
-
120 days


Sensitive to sunlight, microbial digestion


Oxidation to
chlorpyrifos

oxon


Little burden
in water supply


Indoor half
-
life


Estimated around 30 days


Accumulates on
sorbant

surfaces

Child vulnerability


Children living in agricultural homes:


Average of 0.52
ug

chlorpyrifos
/ pair of hands


Dermal dose


3% absorption / 3.24 kg newborn = 4.8 * 10
-
8
mg/kg


Oral dose


Hand
-
to
-
mouth behavior


100% absorption / 3.24 kg newborn =
1.6 * 10
-
4
mg/kg


Inhalation dose


30 ug/m
3

24 hours after pesticide application


60 times higher than EPA limit!




Risk Summary



EPA
RfD
: 0.0003 mg/kg/day for children


Prenatal exposure with significant developmental effects:



Approx. 2.59 * 10
-
7
mg/kg at birth


Significant exposures arising from:


Agricultural communities


Drinking water


U.S. allowable lifetime dose = 20
ug
/L


Current standards are woefully inadequate to prevent long
-
term
developmental consequences.



Precautionary Assessment

Community / Social Issues

Parameter

Score

Goal

2

Need

2

Future
Generations

3

Democratic
, community
based process

2

Alternatives

3

Total

12/15

Exposure Issues

Exposure Issues



Exposure

3

Multiple
exposures

3

Children
exposed

5

Consumer
products

3

Occupational
exposure

3

Food
exposure

3

Total

20/20

Hazard/Toxicity



Hazard

9

Individual
Sensitivity

3

Ecological
hazard

3

Volume

5

Persistent

1

Bioaccumulation

2

Uncertainty

2

Total

25/30

Risk Management

Risk Perception


“Pesticide Drift” and children
in California


http://www.npr.org/templ
ates/story/story.php?story
Id=123817702


Dow Chemical on
Chlorpyrifos

and kids


http://www.chlorpyrifos.c
om/myths
-
vs
-
facts.htm


Registration review


Docket opened May 2009


Human health assessment


Public comment period July
-
September of this year


Scoping: lack of emphasis on developmental toxicology data!


Environmental/endangered species impact assessment


Public comment October
-
December 2013


Final registration decision in 2015



Recent regulatory action


New limitations to protect salmon, steelhead under Endangered
Species Act announced in September 2009


Created in conjunction with the National Marine Fisheries
Service


New labeling guidelines


Limitations on application: buffer zones, increased
environmental monitoring, fish mortality data

References


Eskenazi
, et al. Exposures of children to organophosphate pesticides and their potential adverse health
effects. 


Fenske
, et al. Children's exposure to
chlorpyrifos

and parathion in an agricultural community in central
Washington State. 


Fenske
, et al. Biologically based pesticide dose estimates for children in an agricultural community. 


Fenske
, et al. Potential exposure and health risks of infants following indoor residential pesticide
applications. 


Gore. Environmental Toxicant Effects on
Neuroendocrine

Function. 


Griffin, et al. Oral and dermal absorption of
chlorpyrifos
: a human volunteer study. 


Gurunathan
, et al. Accumulation of
chlorpyrifos

on residential surfaces and toys accessible to children. 


Rauh
, et al. Impact of Prenatal
Chlorpyrifos

Exposure on Neurodevelopment in the First 3 Years of Life
Among Inner
-
City Children. 


Simcox
, et al. Pesticides in household dust and soil: exposure pathways for children of agricultural families. 


Slotkin

and
Seidler
. The alterations in CNS
serotonergic

mechanisms caused by neonatal
chlorpyrifos

exposure are permanent. 

Resources


EPA
-

Chlorpyrifos

Fact Sheet: 
http://www.epa.gov/pesticides/reregistration/REDs/factsheets/chlorpyrifos_fs.htm



EPA
-

Chlorpyrifos

Risk Information: http://www.epa.gov/iris/subst/0026.htm 


EPA
-

Chlorpyrifos

Interim Risk Management Decision:
http://www.epa.gov/oppsrrd1/reregistration/chlorpyrifos/ 


ATSDR
-

Chlorpyrifos

ToxFAQs
: http://www.atsdr.cdc.gov/tfacts84.html 


Pesticide Action Network


Chlorpyrifos
:
http://
www.pesticideinfo.org/Detail_Chemical.jsp?Rec_Id
=PC33392 


National Agricultural Statistics Service
-

Agricultural Chemical Use Database:
http://
www.pestmanagement.info/nass/app_usage.cfm



National Resources Defense Council
-

Our Children At Risk:
http://www.nrdc.org/health/kids/ocar/chap5b.asp 


Dow Chemical
-

Chlorpyrifos

Protects: http://
www.chlorpyrifos.com
/ 


NPR
-

"Pesticide drift eluding efforts to combat it",
2/28/10:http://www.npr.org/templates/story/story.php?storyId=123817702 

Questions?