Public Health 150
Environmental Health
John R. Froines, PhD
Department of Environmental Health Sciences
Pesticides and Fumigants: Fate and
Transport: Major CA controversy
Fumigant use in California
• Methyl iodide: Proposed use primarily for
strawberries-methyl iodide to replace methyl
bromide
• Chloropicrin
• Metam sodium
• Methyl bromide
• 1,3-dichloropropene (telone)
• Historically: DBCP and ethylene dibromide
Methods of Application
Shank injection application
Bedded tarped application
Geographic Trends in Fumigant Use
Use of Soil Fumigants in California, 1988–2010
Metam Na&K
Methyl Bromide
Chloropicrin
1,3-Dichloropropene (Telone)
40
30
20
10
0
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Millions of pounds
of active ingredient
50
> 5 PCT
Criteria
>1
million
pounds
Total
Pounds
Crop
Chloropicrin
Metam Sodium
Methyl Bromide
Potatoes
Pounds
200,000
Tomatoes
Tobacco
Carrots
Strawberries
Peppers
Watermelons
Onions
Cucumbers
Peanuts
Cantaloupes
Sweet Potato**
Squash
Cabbage
Eggplant
Celery
Artichokes
Brussels
Sprout**
Almonds
Walnuts
Cotton
Sugar Beets
Grapes
PCT
<1
Pounds
31,700,000
PCT
20
Pounds
200,000
PCT
<1
1,700,000
10
7,000,000
15
20
300,000
<1
19,600,000
3,600,000
70,000
1,400,000
700,000
800,000
200,000
100,000
5,000
100,000
100,000
80,000
15
<1
20
10
<1
<1
5
<1
5
6
<1
100,000
9,000,000
200,000
700,000
700,000
1,700,000
300,000
1,100,000
800,000
300,000
100,000
60,000
6,000
200,000
50,000
60,000
<1
40
<1
5
2
5
<1
5
5
1
<1
<1
<1
10
5
30
10,600,00
0
500,000
70,000
7,600,000
3,700,000
2,300,000
200,000
1,300,000
<1
<1
50
20
5
<1
5
800,000
800,000
400,000
5
5
5
7,800,000
1,500,000
400,000
200,000
400,000
900,000
900,000
1,300,000
300,000
800,000
200,000
200,000
10
10
5
5
<1
5
10
<1
5
20
5
5
200,000
45
60,000
45
12,000,000
10,640,000
9,600,000
5,300,000
4,200,000
3,000,000
2,600,000
2,405,000
2,000,000
2,000,000
780,000
260,000
206,000
200,000
50,000
120,000
7,000
5,000
<1
<1
2,500,000
1,700,000
<1
<1
400,000
7,000
<1
<1
600,000
<1
200,000
100,000
1,100,000
700,000
500,000
<1
<1
<1
<1
<1
2,807,000
1,825,000
1,300,000
1,160,000
1,115,000
100,000
20,000
200,000
60,000
8,000
<1
<1
<1
<1
<1
1,3Dichloropropene
Pounds
PCT
9,900,000
5
Total
Pounds
42,000,000
*Notes: Crops are grouped using criteria of greater than 5 percent of the crop treated (PCT) of at least one fumigant, greater
than one millions pounds active ingredient used annually of at least one fumigant, or more than a million pounds active
ingredient used of one or more of the soil fumigants. This table does not include values (based on EPA data) for metam
potassium, as follows: Cucumber- 120,000; Onions- 130,000; Peppers- 450,000; Potatoes- 1,300,000; Tomatoes- 350,000;
Watermelon- 450,000 pounds.
Sources: Reference 16
Table data was taken from BEAD Screening Level Usage Analyses (SLUA) unless otherwise indicated.
** Data are from the National Center for Food and Agricultural Policy, 1997 National Pesticide Use Database.
**Data are from the California Department of Pesticide Regulation, 2001 and 2002 Pesticide Use Reporting Database.
Age
Sex
Circumstances
Symptoms
30 years
i
Male
Methyl iodide synthesis
Method not specified
35 years
ii
Male
Methyl iodide synthesis, from
dimethyl sulfate and
sodium iodide
Open method: exposure to
methyl iodide vapors
34 years
iii
Male
Methyl iodide synthesis from
methanol and sodium
iodide
Open method: exposure to
methyl iodide vapors
Latency period not specified
Vertigo, ataxia, diplopia.
From day 5: agitation, confusion and delirium
Gradual recovery starting at day 12
21 months after exposure: Persistent cognitive deficit and
personality disturbances
Episodes of giddiness and sleepiness
On re-exposure: drowsiness, ataxia, dysarthria, nystagmus,
strabismus
Twitching of the extremities and vomiting; then coma
Day 8 after exposure: Death
Post-mortem examination: congestion of all organs
Symptom-free for 2 days post-exposure
Days 3–4: Drowsiness, diplopia, ataxia
Days 5–6: Semi-comatose condition with nuchal rigidity,
strabismus, and vomiting
Days 7–12: Nystagmus and cerebellar signs with
adiadokokinesis, dysmetria, ataxic gait, dysarthria; diffusely
abnormal EEG
Days 13–60: Gradual disappearance of the neurological
symptoms and normalization of the EEG
Days 61–99: Psychiatric syndrome with hypochondria,
depression, and insomnia
30 years
iv
Male
Occupational exposure to methyl
iodide vapors
35 years
v
Male
Occupational exposure to methyl
iodide vapors
38 years
vi
Female
Occupational exposure to methyl
iodide vapors
Contamination of clothes with
liquid methyl iodide
41 years
vii
Male
Methyl iodide synthesis
Method not specified
Prolonged exposure to methyl
iodide vapors
Dermal contamination (right
thumb)
Female
Handling of methyl iodide with
rubber gloves
Intravenous injection of 6 mL (14
g) methyl iodide
Counteracted by administration
of N-acetylcysteine
viii
Adult
19 years
ix
Male
Days 100–121: Progressive recovery
Headache, diplopia, vertigo, ataxia, dysarthria, then agitation,
nystagmus, and cerebellar syndrome; diffuse EEG abnormalities
Clinical recovery within 5 months but persistence of EEG
abnormalities
Headache, vertigo, ataxia, dysarthria; then cerebellar syndrome,
pyramidal syndrome, hallucinations, and delusions
Gradual improvement within 5 months but persistence of
hindering neurological sequelae
Symptom-free interval of 24 hours
Dizziness, weakness
Day 3: Diplopia, ataxia, dysarthria, tetraparesis
Day 4: Auditory hallucinations and delusions
Gradual improvement within 2 months
One year later, persistence of disabling sequelae: ataxia and
dysarthria
Blurred vision and unsteadiness of gait during exposure
Symptomfree interval of a few hours
Diplopia, dysarthria, ataxia, dysmetria, nystagmus, confusion,
drowsiness
EEG: diffuse slow waves
Chemical burn of the contaminated thumb
Gradual improvement during the first 3 weeks
Then, auditory and visual hallucinations, paranoid ideation, and
delusions
Gradual recovery within 5 months
Chemical burn of the hands
No systemic reaction
Drowsiness, agitation, hypotension, hyperthermia
Metabolic acidosis, hyperleucocytosis
Serum methyl iodide concentration: about 60 pg/mL, 3 hours
after injection
Treatment: Hemoperfusion and N-acetylcysteine administration
Complete recovery within 5 days
MeI Risk Characterization
MeI Risk Characterization
P 82
Table VI: Variability in late resorption data rabbits exposed to MeI by inhalation during gesta
to 28.
Late Resorption
Number of litters
Number of
implantation sites in
each litter
Affected litter
Range of % fetus
affected in affected
litter
Range of % fetus
affected for all litters
Mean % fetus
affected/litter
Dose (ppm)
0
23
2 to 11
2
20
1 to 11
10
20
2 to 10
20
21
1 to 10
2
10.0%
28.6%
2
16.7%
45.5%
6
12.5%
to 71.4%
11
10.1%
to 87.5%
0 to 28.6%
0 to 45.5%
0 to 71.4%
0 to 87.5%
1.7±6.2%
3.1±10.7%
11.1±21.2%
21.5±26.9%
P 84
Table VI-8: Reference concentrations for MeI inhalation exposure.
P 106
MeI Risk Characterization
Table VII-Error! Main Document Only.: Reference Concentration Scenarios
Scenario
Bystander RfC
Source
I
Worker
RfC
(ppb)
0.8
0.3
DPR
Risk
Assess
ors/
SRC/
OEHH
A
II
8
3
III
15
5
IV
30
10
V
51
17
VI
96
32
DRP
Risk
Manag
ers
DRP
Risk
Manag
ers
DRP
Risk
Manag
ers
DRP
Risk
Manag
ers
DRP
Risk
Manag
ers
Application
Method
Drip
Drip, Bedded
Shank,
Broad- cast
Shank
Drip, Bedded
Shank,
Broad- cast
Shank
Drip, Bedded
Shank,
Broad- cast
Shank
Drip, Bedded
Shank,
Broad- cast
Shank
Drip, Bedded
Shank,
Broad- cast
Shank
Conclusions Regarding Mitigation
· Buffer zones would be “excessive and
difficult to enforce.” “The registrant may
find these buffer zones unacceptable due
to its economic viability.”
· Regarding worker protection mitigation for
drip application, observing that “the
registrant may find these mitigation
measures unacceptable.”
Regarding worker protection mitigation for
shank application, observing that “the
registrant may find these mitigation measures
unacceptable.”
Regarding worker protection mitigation for
shank application, observing that “the
registrant may find these mitigation measures
unacceptable.”
Regarding worker protection mitigation for
shank application, observing that “the
registrant may find these mitigation measures
unacceptable.”
Regarding worker protection mitigation for
shank application, observing that “the
registrant may find these mitigation measures
unacceptable.”
Regarding worker protection mitigation for
shank application, observing that “the
registrant may find these mitigation measures
unacceptable.”
Key industrial toxics
recognized for a
considerable period
16
“Safe” air concentration of benzene (TLV)
has declined 200-fold in 50 years
100
Benzene recognized
since fifteenth century;
Exposure to benzene
in the air causes
leukemia, a potentially
fatal cancer of the
blood. Including acute
myeloid leukemia or
acute non-lymphocytic
leukaemia.
90
80
100ppm
TLV (ppm)
70
60
ACGIH TLVs for Benzene, 1946 -1997
50
40
30
0.5ppm
20
10
0
1940
1950
1960
1970
Year
1980
1990
2000
IARC rated benzene
as "known to be
carcinogenic to
humans"
ENVIRONMENTAL HEALTH
• “Environmental health comprises those
aspects of human health, including quality of
life, that are determined by physical, chemical,
biological, social, and psychosocial processes
in the environment” (WHO).
• The science and knowledge we bring to the
looming environmental crises must evolve to
enable prevention/control and protection of
public health.
THE ENVIRONMENT IS
A POWERFUL DETERMINANT OF HEALTH,
As Nations Develop, Patterns of Disease Change Profoundly
• Infectious diseases decline in frequency and severity (AIDS
and tuberculosis notwithstanding)
• Life expectancy increases
• Infant mortality declines
• Chronic diseases such as cancer and cardiovascular, become
increasingly prevalent
The Epidemiologic Transition
Traditional Diseases,
e.g. infectious
Modern, e.g.
non-communicable
Non-transitional, e.g.,
injuries
Not mortality, i.e., Life span; die later
Environmental Health
• Environmental health problems were local in
their effects and short in duration
• Todays problems are persistent and global
• Problems not amenable to quick technical
fixes
• Problems require fundamental shift in culture,
politics and attitudes; we must change the
SOCIAL ENVIRONMENT
• 1970s-Death from coronary heart disease: 1.2 x greater in
men in lowest social class
• 1990s-Ratio increased to 2.2
• Today a 3 fold inverse gradient in coronary heart disease
mortality
• How do we explain what appears to be class differences?
Environmental successes during the past
century?
• What were the key environmental successes
during the past century?
– Decline in infectious disease
– Smoking and cancer
– Elimination of lead from gasoline and paint
– Seat belts
– Fluoride in water
•The social environment
Patterns of Disease Change with Development
Environmental Change is the Driving Force
Rates of homicide in Chicago and England and Wales by age and sex of perpetrator; homicide rate is
a reflection of a disorder society-how to change-Given testosterone antagonist?
Emphasis on addressing environmental health problems in terms of media,
constituencies-new areas
•Media
–Air
–Water
–Hazardous waste
–Pesticides
–Food
–Soil
•Constituencies
–Occupational health
•Mining
•Work environment
In utero, children, long term impact
neurological, endocrine disruption
•Global issues
–Global warming
–Ozone depletion
–New technologies
–Impact of globalization
–Population
–Climate
–Habitat destruction
–Biodiversity
–Consumption
–Resources
•New areas of emphasis
–The built environment
–Urban Sprawl
–Psychosocial factors
–Behavioral issues
–Obesity
Relevant tools at our disposal for studying
sourcehealth effect
• Exposure assessment including physical/chemical
characterization of toxic agents
• Structure-activity relationships
• Toxicology including chemical, biological toxicology and in vivo
studies
• Epidemiology including genetic epidemiology and molecular
epidemiology
• Biological and chemical mechanisms
• Case studies
Policy related issues
• Decisions, decisions decisions-how do we decide whether a
chemical is toxic, poses a risk to humans, and what are
intervention strategies for control?
• What is the level of proof required for intervention and
control to protect public health? Science and policy
• What are the criteria for these decisions? Science and policy
• Need for alternatives analysis
• Example of all this: what is a CARCINOGEN? Once we decide
what is our policy for addressing it.
Increases in concentration of lead in Greenland*
Lead is ubiquitous
Lead is
ubiquitous
*shown on a logarithmic scale.
McMichael, T. (2001). Human frontiers, environments, and disease. Cambridge, UK, Cambridge University Press.
large populations of children. These actions comprise the core elements of a global strategy to
end childhood lead poisoning
To end childhood lead poisoning in countries around the world, five achievable actions,
with a proven track record of success in lowering blood lead levels in large populations
of children must be implemented. These are:
1) Complete the removal of lead from gasoline.
2) Ban all other non-essential uses of lead.
3) Remove lead from paint and solder in canned food.
4) Set and enforce enforceable standards for lead in paint, soil, dust, water and air.
5) Establish blood lead levels of concern that are consistent with current science on lowlevel lead toxicity in children.
To achieve the goal of ending childhood lead poisoning worldwide, this document offers
evidence-based guidance for health care authorities, policy makers, health care providers and
Figure 1 : Source: Norm Healy
re 2 (Source: Bruce Lanphear) (Lanphear et al., 2004) (Maybe Bruce has
graph)
33
Advertisements by National Lead Company from
1923-1935
34
Putting lead in gasoline in the 1920s has been called
“the worst environmental decision of the 20th century.”
Ethyl
Gasoline
Corporation
Ad in
1923
35
Arsenic
• Air
– Burning fossil fuels
• Food
– Vegetables and fruits (Due to pesticides/herbicides)
– Meat consumption esp. seafood.
• Water
– Weathering of Rocks
– Non-ferrous metal smelting
• Soil
– Same as water
– Wood preservatives
– California example: Owen’s lake
Taiwan
Chile
Argentina
As. “Hotspots”
2002
Arsenic in Bangladesh and West Bengal
• 1970s and 1980s - International aid to drill
tube wells and improve water supplies
• 1983 - First skin lesions detected
• Estimated populations exposed:
– Bangladesh: 35-77 million (of 125 million)
– West Bengal: 1.5 million
Hyperkeratosis
Arsenic carcinogenicity by ingestion in
drinking water
Comparison of Smith and Cal/EPA
As exp. for risk As exp. for risk
of 10-3
of 10-6
(PHG)
Cal/EPA
Smith
4 mg/L
4 ppb
0.004 mg/L
4 ppt
2.5 mg/L
2.5 ppb
0.0025 mg/L
2.5 ppt
History
• First Air Pollution Commission: 1265-1306
– Recommended banning coal in London
– Implementation delayed for ~650 years
– London, UK: 1952 (Smoke + Fog = Smog)-no wind,
inversion-stagnant
How small are these particles?
Hair cross section (60 mm)
Human Hair
(60 mm diameter)
PM10
(10 mm)
PM0.1 PM2.5
(0.1 mm) (2.5 mm)
Aerosol Toxics
adsorbed toxics
vapor-phase toxics
condensed-phase toxics
Ultrastructural analysis of lung tissue found inhaled ultrafine
particles were located within the epithelial barriers, cytoplasm,
mitochondria and the nucleus of cells.
Particle Counts in the L.A. Basin
Location where measured
Coastal air
Particle count – number
of particles per cubic
centimeter
600
San Pedro (near Harbor)
42,000
110 Freeway (area with no
diesel trucks)
135,000
710 Freeway, Long Beach
(high percentage of diesel
trucks
300,000-600,000
710 Freeway, maximum
measured
3,000,000
Credit: Dane Westerdahl, Scott Fruin
Size of sugar cube
Summary: Health effects associated with
PM exposure
• Effects on CNS and autonomic nervous system
• Low birth weight/preterm babies
• Increase in asthma and other respiratory disease
in children and adults
• Decrease in lung development and function in
children
• Atherosclerosis in adults
• Cancer
Findings on Epidemiologic Studies on
Carcinogenicity of Diesel exhaust
• More than 40 studies
• These studies have found that long-term
occupational exposures were associated with
a 40% increase in risk of lung cancer.
• Findings are consistent and unlikely due to
chance.
• A causal relationship between occ. diesel
exhaust exposure and lung cancer.
• Risk about 1 excess cancer/10,000/ug/m3
MATES-II Assessment of Cancer
Risk in LA Basin
Basinwide Cancer Risks* ~1400 in a million
11%
3%
7%
Diesel Particulate
8%
1,3 Butadiene
Benzene
71%
Carbonyls
Other
710 Freeway - Trucks
• Today: 33,000 a day
• 2020: 120,000 a day
• International vehicles not
effectively regulated
• What does this about our
culture, accidents, noise, air
pollution, overall quality of
life, walkability, tire debris,
particular problems for
children
• Examines cancer
clusters throughout LA
county over 25 year
period
New Cancer Cluster Study
USC, School of Medicine
• Both LA and LB port
Professor T. M. Mack
communities identified
having high cancer rates
Deposition and Pathways of Particle Translocation Within and
Outside Respiratory Tract--Main Mechanism for UFP is Diffusion
Translocation of UFP from
NP and TB region along sensory
neurons to CNS (neurodegeneration)
•Translocation of UFP to
interstitium, capillaries, heart
•Uptake by endothelium; platelets
•Activation/interaction of endothelial
cells, platelets and leukocytes
Alveolar inflammation
Untreated
Mag. x 6000
Mag. x 21000
M
Coarse
M
P
P
Ultrafines lodge in and destroy mitochondria
Mag. x 6000
Mag. x 21000
RAW 267.4
P
P
M
M
M
M
Animal Model to Study PM Effect on Allergic Sensitization
OVA
OVA + UFP
Major basic Protein
AB/PAS
(Eosinophils) (Mucosubstances)
H&E
(Morphology)
Saline
Li et al, Environ Health Perspect, 2009
Summary
 UFP
are capable of acting to enhance
the primary allergic sensitization
response to experimental allergens
 Inhalation of “real-life” UFP could lead
to a profound allergic inflammation deep
in the lung in previously sensitized
animals
Oxford Street,
London, UK
(Exposure Site)
Hyde Park, London
(Control Site)
Persons with asthma, accompanied by study staff, walking
at Hyde Park site (duration: 2 hours)
Mean and SE of % Change from Baseline
for FEV1
2
FEV1, mild asthma
Control
Exposure
2
FEV1, moderate asthma
Control
Exposure
0
% Change from baseline
% Change from baseline
0
-2
-4
-6
-8
-2
-4
-6
-8
-10
-10
0
2
4
6
8
20
22
0
2
Time (hr)
d.f=(6, 272)
F=0.86
4
6
8
20
Time (hr)
p=0.525
d.f=(6, 244)
F=1.84
p=0.093
22
Adverse Effects on Lung Function and
Airway Inflammation
The reduction in lung function (FEV1 and FVC) was
accompanied by increased airway inflammation
We consider inflammation of the lung and heart to be
fundamental issues in disease and illness especially
lung and cardiovascular
We have shown the pathway (roadmap) from exposure
to changes in cells to inflammation and health effects
Results: More asthma within 150 m of major roads
Children aged 5-7-lifetime asthma, prevalent asthma, and wheeze
Asthma Odds Ratio
2.5
2
1.5
1
0.5
0
<75
75-150
150-300
>300
Distance to Major Road (meters)
McConnell, et. al. AJRCCM 2005;2:A522
Experimental Design: apoE-/- mice
PM promotes atherosclerosis
E-/Chow
Non-exposed
(NE)
*
Filtered air
(FA)
6-week-old male
Exposures: 5 hours/session
3x/week for 5 weeks
PM2.5
(FP)
Aortic atherosclerosis assessment
PM0.1
(UFP)
Aortic lesions-UFP result in most significant impact with
respect to atherosclerosis
Araujo J, 2008
Aortic lesion area (mm2/section)
Aortic atherosclerotic lesions
70000
P<0.0001
P= 0.002
60000
P= 0.02
P= 0.02
50000
40000
30000
20000
10000
0
NE
FA
Condition
FP
UFP
Cardiovascular Health and Air Pollution
Study-Health outcomes.
• Blood Pressure
• Evidence of ischemia-a restriction or
thinning in blood supply
• Airway inflammation produces
immunological response and
exacerbation of atherosclerosis
Offshoring: Imported electronic waste, Lianjiang River, Guiyu,
China All China photos copyright 2001, Basel Action Network
Electronic waste recovery workers, Guiyu, China
Toner recovery worker, Guiyu, China
Carbon black (IARC 2A carcinogen); cartridge dumping
Risk assessment
Erin Brockowitch-Carcinogenicity Evidence
• Cr VI is known to cause lung, nasal and/or sinus
cavity cancers in humans (30 occupational studies)
• There is suggestive evidence of distant tumors in
humans (bladder-stomach)
• Key-oral intake-valence state
• Cr VI causes tumors in laboratory animal studies by
multiple exposure routes
• Cr VI is genotoxic animals and cells, inducing DNA
damage, gene mutation, chromosomal damage
• IARC: “Cr VI is carcinogenic to humans”
Key issue
• “The greater absorption of Cr(VI) than of
Cr(III) implies that absorption from the
gastrointestinal tract is so rapid that it is
able to compete effectively with
reduction in the stomach.”
• O’flaherty et al., Toxicological Sciences, 60, 196-213,
2001
Chromium VI and cancer
• Results of a study by the National Toxicology Program
• Male and female rats and mice
• Significant increases in tumors at sites rarely seen in
lab animals
• Oral cavity and (mice) small intestine (doseresponse)
• Chromium VI is a potent human carcinogen, but still
widely used-are there alternatives-high priority, why
is the State not proactive