Transcript Health Hazards of Pesticides - AOEC

Pesticide Illness
Part 3
Fumigants, Fungicides,
Herbicides, Disinfectants,
Miscellaneous Pesticides
Prepared by:
Rupali Das, MD, MPH, California Department of Health Services,
Michael O’Malley, MD, MPH, University of California, Davis,
Laura Styles, MPH, Public Health Institute
Toxicology, Diagnosis &
Management of Pesticide Illness by
Functional Category
 Insecticides
 Fumigants
 Fungicides
 Herbicides
 Disinfectants
 Miscellaneous
2
Fumigants

Halogenated hydrocarbons
– Methyl bromide
– Ethylene dibromide, DBCP

Inorganic compounds

US DOT
– Sulfuryl fluoride
Pro-fumigants
– Metam sodium

Metal phosphides
– Aluminum, Zinc, Magnesium
3
Fumigants
Methyl Bromide
H
Br
C H
H
 High
vapor
pressure
 Heavier than air
 Odorless
– Chloropicrin added
 Toxic
mechanism
– Tissue methylation
4
Methyl Bromide Acute Toxicity

Vesicant
– Blistering dermatitis

Lower respiratory toxicant
– Delayed pulmonary edema

Central nervous system
depressant
– Usual cause of death
5
Methyl Bromide Acute Toxicity
Differential Diagnosis
 CNS
depression
– Other CNS depressants
 Pulmonary
edema
– Hepatic & renal disease
– Acute severe asthma
6
Methyl Bromide Acute Toxicity
Management

Serum bromide
levels
– 3-6 ppm: Possible
exposure
– >15 ppm: Acute
poisoning
– >50 ppm: Severe
poisoning/ death

Treatment
Bromide levels - Reporting
units
 ppm = mg/liter
 mg/L=10 mg /deciliter
(USA)
 ppm = 80 milli-equivalents
(meq)/liter (European)
– Symptomatic
7
Methyl Bromide Chronic Toxicity
 Central
nervous system
– Cognitive, behavioral effects
– Polyneuropathy
 Reproductive
system
– Teratogen
– Genotoxic, mutagenic
8
Methyl Bromide Chronic Toxicity
Serum Bromide Levels
 Long
serum half life
– 11—15 days
 Chronic
exposure
– Asymptomatic high
levels possible
9
Case
Illness After House Fumigation
10
Illness After House Fumigation
Pesticide Application History
Methyl bromide
fumigation
Uncovered electrical conduit: one pipe had
a 2” diameter and the others a 1” diameter
11
Illness After House Fumigation
Health Effects



Tenant found convulsing on floor
the following evening
Serum bromide level 270 ppm
Refractory seizures, intermittent
fever, multi-organ failure
12
Methyl Bromide Phase-out
 Ozone
depletion
– “100% reduction” in
2005
 Exemptions
– Critical agricultural uses
– Pre-shipment &
quarantine
– Emergency uses
 No
“ideal”
substitute
Source: US EPA “Frequently Asked Questions” 13
on methyl bromide phase-out
Fumigants
Sulfuryl Fluoride
O
O S
 Pulmonary
F
F
Sulfuryl fluoride
– Dyspnea, cough, delayed pulmonary
edema, fatal hypoxia
 Renal
 CNS
– Weakness, nausea, vomiting,
restlessness, muscle twitching,
seizures
14
Fumigants
Metam Sodium
S
CH3NH
Na+ . 2
C
S
 Hydrolyzes
S
CH3NH
Na+ . 2 H2O
C
to mixture of irritants
H2O
CH3N
MITC
S
+ CH3
NH2
Methylamine
 Health
C S
+
CH3N
C O
MIC - up to 4% of the
level of MITC
+ CS2
Carbon disulfide
+ H2S
Hydrogen sulfide
effects
– Irritant dermatitis
– Reactive airways dysfunction
syndrome/asthma
15
Case
Transportation Worker with Cough
 40
year-old male transportation
worker with metallic taste;
burning eyes, chest, nose;
nausea; dizziness.
 Recurrent
cough with wheezing,
phlegm for 5 days. Chest
tightness, dyspnea on exertion.
16
Transportation Worker with Cough
Exposure History

Tank car derailment
– >19,000 gallons
metam sodium
released

Worker involved in
response to accident
– Symptoms onset
within 20 minutes
– Worked 6.5 hours
alongside river
17
Transportation Worker with Cough
Physical Evaluation
 Exam
6 months later
– Mild nasal inflammation,
– Spirometry
 FEV1:
87%, FVC: 101%,
FEV1/FVC: 69%, FEF25-75:
26%
– Methacholine challenge
test
 PC100:
1.2 mg/ml
(normal >4 mg/ml)
18
Fumigants
Chronic Effects
Neurologic
Methyl
Cognitive,
bromide behavioral
Sulfuryl
fluoride
Metam
sodium
Reproductive
Other
Animal studies
Olfactory,
cognitive
Animal studies RADS,
asthma
19
Case
Drift After Metam Application


Metam sodium
applied to carrot
fields
Illness reported
among
– School children
– Workers
20
California Department of Health Services, 2001
Drift After Metam Application
Investigation Findings
 MITC
Field w here metamsodium applied
~1m
ile
500 f oot buffer zone
School:
w orkers &
children ill
Figure not to scale
Other
workers
exposed
detected at
school, beyond
500 foot buffer
zone
 Workers
required
to monitor field
for odor
21
Fumigants
Phosphide Compounds
 Metal
phosphides
hydrolyze
– Aluminum, zinc, magnesium
 Phosphine
– Colorless, fish/garlic odor
– Highly explosive, corrosive
– Rapidly oxidizes to
phosphoric acid
22
Phosphine: Illness Syndromes
 May
resemble viral syndromes
 Pulmonary
 CNS
toxicity
toxicity
 Multi-organ
failure
23
Case
Fatality After In-Transit Fumigation

Unemployed male
in railcar fumigated
with aluminum
phosphide
Source: BC Workers Comp

Badly decomposed
body found on
arrival at
destination
24
Fungicides
 Thiocarbamates
– Zineb, maneb, ziram, thiram
 Pthalimide
derivatives
– Captan, captafol,
 Substituted
aromatics
– Chlorothalonil, hexachlorobenzene
 Inorganic
– Sulfur
25
Health Effects of Fungicides
 Acute
– Irritant & allergic dermatitis
 Chronic
– Chronic dermatitis
– Possible carcinogens
26
Fungicides: Thiocarbamates
CH3
CH3
 Resemble
rubber
accelerator thiuram
N C S
S C N
S
S
CH3
Thiram
CH3
CH3
N C S
CH3
Zn
S C N
S
CH3
S
Ziram
 Sensitization
reported in exposed
workers
CH3
S
CH2
NH C S
CH2
NH C S Mn
X
X>1
S
Maneb
27
Thiocarbamates
Antabuse-like Reactions
CH3
CH3
N C S
CH3
S C N
S
S
Thiuram
CH3
CH3
CH3
CH3
N C S
S C N
S
S
CH3
Thiram
28
Case
Pear Pickers with Skin Rash
26 people picking pears
complained of skin rashes
 Physical exam:

– Contact dermatitis

Applied five days before:
– NAA 800
– Ziram Granuflo
USDA Graphics
29
Pear Pickers with Skin Rash
Pesticide Application
 Workers
followed requirements for
re-entry
 Ziram applications
– D'Anjou pears, Golden Delicious apples
– Symptoms in Bosc pear pickers only
 Postulated
mechanism of dermatitis
– Sharp latent bud on Bosc pears
– Increased susceptibility to dermal
irritation
30
Pear Pickers with Skin Rash
Regulatory Action
 Re-entry
interval of 14 days
established for formulations of ziram
on Bosc pears
CH3
CH3
N C S
CH3
Zn
S C N
S
S
CH3
Ziram
31
Fungicides: Captan
 Dermatitis
 5%
of volunteers sensitized
O
N
S
CCl3
Captan
O
32
Case
Nursery Worker with Urticaria
Itching and hives in
redwood nursery worker
 Chlorothalonil patch test:

– Local Type I
hypersensitivity

1% chlorothalonil open
test
– Systemic Type I reaction
33
Chlorothalonil: Pigmentary Changes
Blue-gray
pigmentation in
antecubital area
 Positive skin reaction
to chlorothalonil
 Diagnosis: Ashy
dermatitis

34
Ashy Dermatitis: Mechanism


Disruption of
basal membrane
of epidermis
Melanin deposits
in dermis
C N
Cl
Cl
Cl
C N
Cl
Chlorothalonil
35
Panagos et al. 1996
Fungicides: Elemental Sulfur
 Potent
irritant
skin
– Animal
experiments
equivocal
 Airway
irritant
36
Case
Applicator With Skin Irritation
 Pesticide
applicator
applied sulfur dust to
roses
 Contact
dermatitis
– Burning pain
– Maculopapular rash
.
37
Sulfur: Allergic Skin Reactions


Positive patch test
reactions to sulfur
in nursery workers
applying sulfur
Case reports
support sulfurinduced allergy
38
Postulated Mechanism of
Sulfur Irritation and Allergy

1/2 S2O3
SO3
HSO3
pH
temperature
ionic strength
Allergic reactions
– Oxidation/reduction
products
1/2 H2O

Type IV delayed
hypersensitivity
39
Herbicides
 Dipyridyl
compounds
– Paraquat
– Diquat
 Glyphosate
 Phenoxy
compounds
– 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)
– 2,4 dichlorophenoxyacetic acid (2,4-D)
40
 Paraquat
 Diquat
Source: Finnish Platform of the EU-NGDO Liaison Committee
Herbicides: Dipyridyl Compounds
41
Dipyridyl Compounds: Paraquat
 Extremely
ingestion
toxic via
– LD50 3-5 mg/kg
 Toxicity
– Skin, pulmonary
– Parkinson Disease?
42
Hoffer and Teitelman, 1989
Botella et al, 1985
Paraquat Toxicity
43
Paraquat Toxicity: Ingestion

1-4 days
– GI tract edema,
ulcers

NADPH
24-72 hours
– Hepatocellular injury
– Acute tubular
necrosis

Paraquat (PQ)
72-96 hours
– Pulmonary fibrosis
NADP+
PQ2+
O2
O2-
Lipid peroxidation
Cell death
44
Paraquat Levels Predict Outcome
Outcome
Urine level,
24 hours
(mg/mL)1
Survival
<1
likely
Pulmonary 1-1000
fibrosis
Death
within 24
hours
Plasma
level
(mg/kg)2
< 20
20-40
10-10,000 > 40mg
45
Paraquat Toxicity: Treatment
 Skin,
Eye Decontamination
 GI decontamination
 Fluids
 Hemoperfusion
 Oxygen contraindicated
 Severe cases
– High dose steroids and cyclophosphamide
46
Case
Farmer Attempts Suicide
 46
year-old male farmer intentionally
ingested a greenish liquid.
 Complains
of dysphagia, sore throat.
Previous history of depression.
 Profuse,
 Plasma
prolonged vomiting
paraquat at 4 hours
– 3 mg/mL
47
Farmer Attempts Suicide
Hospital Course

Day 2: Severe
dysphagia

Day 3: SOB

Day 4-9: pO2 33.

Day 12: Pt died
due to respiratory
failure.
48
Herbicides: Glyphosate
 Health
effects
– Case reports of eye, skin irritation
– Death due to ingestion of large amounts
– Experimental studies fail to show skin
irritation
 Mechanism
unknown
of human toxicity
– Surfactant preservative?
49
Chlorophenoxy Herbicides
 2,4,5-trichlorophenoxyacetic
(2,4,5-T)
acid
– Derived from tetrachlorobenzene
– Dioxin byproducts
 2,4-dichlorophenoxyacetic
(2,4-D)
acid
– Derived from phenol
– Dioxin contaminants not present
50
Chlorophenoxy Herbicides
 Acute
– CNS depression
– Skin, GI, mucous membrane irritation
– Renal failure, myopathy
 Chronic
– Anemia, hepatic, renal effects
– Tumor formation(?)
51
Antimicrobials & Disinfectants
 Sodium
hypochlorite
 Isopropyl
alcohol
 Gluteraldehyde,
formaldehyde
 Mixtures
– NaOCl + H+ => Cl2
– NaOCl + NH3=> NHCl2, NH2Cl
52
Chlorine Disinfectant Mixtures
Toxicity
 Acute
– Asthma exacerbation,
bronchitis
 Chronic:
– RADS
 Treatment
– Oxygen, bronchodilators
53
Case
Custodian with Shortness of Breath
 29
year-old custodian with cough, sore
throat, shortness of breath after
mixing bleach and ammonia
 Exam:
– Cough, dyspnea, RR=36;
– Lungs: rales & wheezes;
– O2 saturation 94% on room air
– PEFR 80%
54
Miscellaneous Pesticides
 Propargite
(Omite)
O
(CH3)3
C
O
O
S
CH2
C
CH
Propargite
 Diethyltoluamide
(DEET)
O
C
N
C2H5
C2H5
CH3
Diethyl toluamide
55
Acaricide
Propargite Contact Dermatitis
 Sustained-release
propargite
 Severe
dermatitis
with scarring
56
Insect Repellant
DEET Acute Toxicity
 Skin
– Irritation
– Contact urticaria
 CNS
– Seizures,
encephalopathy
 Children
< 5 years
 High
dose/concentrations
57
Acute Toxicity Summary
 Organs
most often affected
– Skin
– Lungs
– CNS
 Severity
greatest in developing
nations
 Exposures occur at work, home, etc.
 Prevention: regulation, substitution
58