Journal of Toxicology

CLINICAL TOXICOLOGY
Vol. 42, No. 5, pp. 579–591, 2004

Health Effects of Diazinon on a Family

J. G. Dahlgren,1,* H. S. Takhar,2 C. A. Ruffalo,3 and M. Zwass2

Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14

1
UCLA School of Medicine, 2James Dahlgren Medical,
3
The Fielding Institute, Santa Monica, California, USA

ABSTRACT

There is increasing evidence of permanent sequalae from acute organophosphate

poisoning. We report on accidental diazinon overexposure with acute organophos-
phate poisoning through cutaneous absorption and inhalation followed by persistent
neurological effects. In addition, we observed skeletal and endocrine effects likely
For personal use only.

attributable to the diazinon poisoning. A family of seven was exposed to diazinon in

June 1999 over a two-day period. The pesticide company mistakenly used diazinon to
heavily spray the inside of the home instead of permethrin. The applicator applied the
pesticide over the entire surface of the floor, carpeting, furniture, and clothing in
closets to eradicate an infestation of fleas. Acute symptoms in the family members
included headaches, nausea, skin irritation, runny nose, and vomiting. The family was
first evaluated at 3 months and then 3 years after the acute poisoning. There were
persisting neurological symptoms of memory loss, decreased concentration,
irritability, and personality changes of varying degrees in all family members.
Objective neurological findings of impaired balance, reaction time, color vision,
slotted pegboards and trials making were present in the three older children who could
be tested. Neuropsychological evaluation revealed evidence of organic brain
dysfunction in all seven family members. Bone growth difficulties are present in
four of five children. One child has delayed menarche.

Key Words: Diazinon; Child; Poisoning; Pesticide; Organophosphate; Effects;

Toxic; Neurotoxic; Encephalopathy; Sensory expressive dysfunction.

*Correspondence: J. G. Dahlgren, UCLA School of Medicine, 2811 Wilshire Blvd. Suite 510, Santa Monica, CA 90403, USA;
E-mail: Dahlgren@envirotoxicology.com.

579

DOI: 10.1081/CLT-200026979 0731-3810 (Print); 1097-9875 (Online)

Copyright D 2004 by Marcel Dekker, Inc. www.dekker.com
 580
INTRODUCTION
In this report we describe the findings in a family,
which was exposed to high levels of diazinon
accidentally applied to their home in June 1999. The
applicator mistakenly used a large amount of diazinon
to broadcast the inside of their home. The family
developed acute organophosphate poisoning and left
the home after 2 days on advice of a physician.
We cannot determine the quantity of diazinon
applied in the home. The diazinon was diluted (as
stated from applicator). The composition of diazinon
Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14
according to Material Safety Data Sheets (MSDS) is
22.4% diazinon and 77.6% inert. We tried to contact
the manufacturer to determine what the inert ingre-
dients consisted of, but were told that information was
confidential and they would be unable to help us.
Organophosphate insecticides can be absorbed
readily through the intact skin or by inhalation (1).
Organophosphates irreversibly bind cholinesterase,
resulting in increased endogenous acetylcholine at
synaptic sites (2). A wide range of toxic manifesta-
tions, including neurological syndrome, occurs because
For personal use only.
this neurotransmitter is present in multiple organs.
The syndrome associated with acute organophosphate
poisoning is the result of nicotinic (ganglionic and
neuromuscular) and muscarinic (parasympathetic) over-
stimulation (2,3).
Poisoning from diazinon exposure has been clear-
ly documented (4,5). The acute neurological effects
from organophosphate overexposure occur within hours
to a few days after onset of exposure (5,6). Acute
central nervous system effects include anxiety, rest-
lessness, irritability, disturbed sleep, reduced concen-
tration, and memory impairment (1,6,7). Permanent
neurological impairment from a single poisoning epi-
sode has been reported, incorporating data from dozens
of cases (6,8 – 10).
The objective of this study is to report some of our
observations, which have not been documented in the
literature, on a family (specifically the children) who
experienced an acute overexposure to diazinon fol-
lowed by permanent sequalae.
MATERIALS AND METHODS
The family first visited our clinic in August 1999.
A history and examination were conducted. The family
returned for a second visit in August 2002. On the
second visit a history and examination were supple-
mented with a battery of neurological tests.
Dahlgren et al.
The entire family underwent a battery of neuro-
logical tests following previously published protocols
(11). Static body balance was measured by head posi-
tional tracking with feet together and arms folded, with
eyes first open and then closed (12). Simple and choice
visual reaction time speeds were measured using a
computerized visual stimulus generator for the letter A
(simple) and for the letters A and S (two choice) (13).
Peg placement was measured using the Lafayette
slotted pegboard (14 – 16). Color discrimination was
measured using the Lanthony desaturated 15 hue test
(17) and scored by the Bowman method (18). Trail
Making A and B from the Halstead-Reitan Battery
were used (19). Visual fields were evaluated using the
Humphrey frequency doubling technique—automated
analyzer (20). Neurophysiological testing included grip
strength using the Jamar Dynamometer. All adult
predicted values for the neurological tests were derived
from a previous publication (11).
The patients were referred for neuropsychological
testing and evaluation, which was conducted by a
neuropsychologist in February 2002 on patients 1 and 2
and in September through November 2002 on patients
3, 4, 5, 6, and 7. Comprehensive neuropsychological
testing was deliberately delayed on the children until
the youngest child reached 3 yrs of age. By the time
neuropsychological testing was accomplished in Octo-
ber 2002 on the 3-yr-old child, he had already been
given a period of some months of remedial interven-
tions by the regional center to address his severe
expressive language impairment.
Exposure Assessment
Associated Labs (Orange, CA) conducted pesticide
sampling on two wipe samples on June 22, 1999. The
floor plan of the home is presented in Fig. 1, which
shows where the samples were taken. The wipes were
extracted using EPA protocols. The wipe ion scans
returned with a 98% quality hit for diazinon.
Associated Labs determined with a 98% assurance
that it was in fact diazinon detected rather than another
organophosphate.
On June 29, 1999, five samples and one control
were analyzed by the state of California, Department
of Pesticide Regulation (samples 3991782 through
3991787). The wipe samples analyzed from the state
of California ranged from 0.0048 – 0.9932 mg per
centimeter squared.
Air sampling was performed on July 9, 1999 (23
days after exposure) by Ensafe (Lancaster, CA) and
tested by DataChem (Salt Lake City, Utah). The
 Health Effects of Diazinon on a Family
Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14
For personal use only.
Figure 1. Floor plan of home.
samples (YGR-0799-01 through YGR-0799-05) were
analyzed using NMAM 5600MOD. Diazinon was
detected at concentrations of 1.9 mg per cubic meter
in the living room, 10 mg per cubic meter in the
playroom, 2.7 mg per cubic meter in the playroom, and
3.3 mg per cubic meter in the kitchen.
Healthscience Associates (Los Alamitos, CA)
conducted air, wipe, and bulk sampling on July 10,
1999, December 1, 1999, and February 29, 2000.
The samples collected by Healthscience Associates
were then analyzed by Armstrong Forensic Laboratory
(Arlington, TX). The air and bulk samples were ana-
lyzed using EPA methods. The diazinon air samples
ranged from .0037 – .0183 mg/m3. The diazinon wipe
samples ranged from 0.2– 1.1 ug/cm2. A sample from
the bulk carpet from the master bedroom was 255 mg/
kg (ppm) 24 days after exposure. The diazinon bulk
samples ranged from 1.18 – 4.72 mg/kg (ppm) at 6.5
months after exposure. Two of 11 samples (bulk, air,
and wipe) were positive for diazinon on follow-up
testing in February 29, 2000. A wipe sample of
581
0.0004645 ug/cm2 was noted at 8 months after
exposure on the carpet in the living room. Negative
follow-up diazinon results are not shown. The quali-
tative and quantitative results of the wipe, air, and bulk
samples are in Tables 1, 2, and 3, respectfully. The
data from Currie (21) were included in our tables
for comparison.
Figure 2 compares the diazinon air levels pub-
lished by the Currie (21) study and the diazinon air
levels found in our study (we extrapolate our air
exposure data back to hour 0 using diazinon half-life
information). The Currie study determined that con-
centrations of diazinon were so high that building
occupants should not enter unventilated rooms for at
least 2 days after spraying indoors with diazinon (21).
A notable point that the Currie study discovered was
that the highest concentrations of diazinon 163 and 158
ug/m3, were measured 4 h after spraying in the two
empty offices (21). In addition, the surface concen-
trations levels were higher at 24 or 48 h (48 h sample
concentration was 38 ng/cm2) than at hour 1 (21).
 582 Dahlgren et al.

Table 1. Wipe sample results.

Study residence Currie, 1990 (21)

Time after Office 1 Office 2

exposure Sample ID Description Exposure data Exposure data Exposure data

1 – 2 hour 6220 ug/cm2 4860 ug/cm2

Day 1 5780 ug/cm2 5000 ug/cm2
Day 8 128499A Tile 98% quality hit
Day 8 128500A Tile 98% quality hit
Day 8 3991782B Outside residence—control 0.00006 ug/cm2
Day 8 3991783B Floor tile in playroom 3.633 ug/cm2
Day 8 3991784B Base of childs toy and back of 0.048 ug/cm2
Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14

two legs of child’s plastic chair

Day 8 3991785B Base of child’s toy and two legs 0.726 ug/cm2
of child’s plastic chair
Day 8 3991786B Floor tile in playroom 5.813 ug/cm2
Day 8 3991787B Playroom by closet 9.932 ug/cm2
Day 24 B82311C Tile—bonus room 0.26 ug/cm2
Day 24 B82312C Child’s room toy in bedroom 1.1 ug/cm2
Day 24 B82312C Child’s toy in middle bedroom 0.4 ug/cm2
Day 24 B82314C Child’s toy in bonus room 0.8 ug/cm2
Day 24 B82316C Hockey equipment in garage 0.2 ug/cm2
Month 8 Y-6C Carpet and pad from living room 0.0004645 ug/cm2
near wall opposite fireplace
For personal use only.

A
Associated Labs (Orange, CA).
B
State of California, Department of Pesticide Regulation.
C
Armstrong Forensic Lab (Arlington).

Table 2. Air sample results.

Study residence Currie, 1990 (21)

Time after Office 1 Office 2

exposure Sample ID Description Exposure data Exposure data Exposure data

0 163 (ug/m3) 158 (ug/m3)

1 125 (ug/m3)  75 (ug/m3)
2  40 (ug/m3) 53 (ug/m3)
6 35 (ug/m3) 35 (ug/m3)
23 days YGR-0799-01A Living room 1.9 ug/m3
23 days YGR-0799-02A Playroom 10 ug/m3
23 days YGR-0799-03A Outdoors adjacent to ND*
AC unit
23 days YGR-0799-04A Child’s room #1 2.7 ug/m3
23 days YGR-0799-05A Kitchen 3.3 ug/m3
24 days B82306B Bonus room 0.0183 mg/m3
24 days B82307B Kid’s bedroom (center) 0.0041mg/m3
24 days B82308B Living room on piano 0.0034 mg/m3
24 days B82309B Kitchen counter 0.0037 mg/m3
24 days B82310B Backyard—control < 0.0007 mg/m3
A
DataChem (Salt Lake City, Utah).
B
Armstrong Forensic Lab (Arlington, TX).
*ND—Non Detect < 0.053 ug/m3.
 Health Effects of Diazinon on a Family 583

Table 3. Bulk sample results.

Study residence
Time after
exposure Sample ID Description Exposure data

Day 24 B82315 Bulk carpet from carpet in master bedroom 255 mg/kg
6.5 months CY – 1 Drywall between kitchen and dining room ND
6.5 months CY – 2 Baseboard between kitchen and dining room ND
6.5 months CY – 3 Acoustical ceiling material near laudry room ND
6.5 months CY – 4 Sofa material from family room near kitchen—near floor 4.72 mg/kg
6.5 months CY – 5 Sofa cushion from family room near kitchen 4.83 mg/kg
6.5 months CY – 6 Carpet & pad from living room near wall opposite fire place 1.22 mg/kg
6.5 months CY – 7 Carpet and pad from master bedroom under workstation ND
Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14

6.5 months CY – 8 Toy from floor of child’s room near garage 1.55 mg/kg
6.5 months CY – 9 Children’s clothing from top of dresser in child’s bedroom near garage 1.18 mg/kg
6.5 months CY – 10 Drywall from garage near hockey equipment ND
6.5 months CY – 11 Drywall from wall opposite fireplace in living room ND
6.5 months CY – 12 Baseboard from wall opposite fireplace in living room ND
6.5 months CY – 13 Toy from child’s room floor near garage ND
*ND—Non Detect (< 1.0) mg/kg.

CASE REPORTS pyrethriods. Subjects 1 and 6 returned to the home

about 4 h after application. Patient 6 crawled on the
For personal use only.

The family, presumably in good health, consisted
of two adults (Patient 1: mother, age 37 and Patient 2:
father, age 39) and 5 children (Patient 3: daughter, age
11; Patient 4: daughter, age 8; Patient 5: son, age 6;
Patient 6: son, age 1; Patient 7: son, in utero at 5
months gestation). They were exposed to diazinon on
June 16, 1999 as a result of an error by the applicator
who applied diazinon for flea control instead of
floor while it was still visibly wet with the pesticide.
The pregnant mother attempted to remove the excess
sticky liquid from the wet floor with a mop using hot
water and tile cleaner and detergent, but she was not
entirely successful. The liquid from the mopping
splashed onto her exposed legs, hands, and arms. She
noticed a burning sensation in her skin where the
chemical touched the skin.

Figure 2. Diazinon air levels.

 584
Subject 6 experienced rhinitis, lacrimation, severe
headaches, muscle pain, and erythema on his face,
arms, and legs that had been in contact with the liquid
on the floor (a summary of the family’s acute and
chronic symptoms is charted in Tables 4 and 5).
Subjects 3, 4, and 5 returned home from school
about 5 h after the application. They also reported
experiencing burning sensations on the skin on their
legs from the pesticide-contaminated home. We infer
that the children most likely were contaminated from
the contaminated carpet, floor, clothing, and furniture.
Patient 3 and 4 had acute headaches and patient 4 had
Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14
repeated episodes of vomiting. Patient 2 came home
later that evening. The next evening patient 2 played
hockey in a pesticide-contaminated hockey uniform.
While playing he experienced vomiting, shortness of
breath, nausea, coughing, dizziness, headache, sweat-
ing, stinging, running nose, and eyes watering and skin
burning. He has subsequently developed chronic
bronchitis despite no history of respiratory problems.
He also has evidence of neuropsychological damage as
diagnosed by the neuropsychologist (a summary of the
family neuropsychological results is given in Table 6).
For personal use only.
Due to the entire family’s acute illnesses they
sought medical treatment in a hospital emergency room
(ER). The ER physician advised the family to im-
mediately evacuate the contaminated home. A urine
sample was tested for diazinon parent compound and
the results were negative. Testing for neither diazinon
metabolites nor cholinesterase levels was done. They
moved back into the house 11 months later after a
thorough cleaning.
The family first visited our clinic in August 1999.
The still-pregnant subject 1 had persisting fatigue,
insomnia, and decreased short-term memory. Subject 2
reported continuing nasal congestion, attacks of
shortness of breath with wheezing, nausea, vomiting,
headache, lightheadedness, drowsiness, insomnia, lack
of concentration, decreased short-term memory, diffi-
culty driving, mood swings, and depression. Physical
examination was normal with the exception of
decreased deep tendon reflexes.
Subject 3, the 11-yr-old daughter, has persistent
severe headaches. The 8-yr-old daughter (subject 4)
had intermittent erythema. The 6-yr-old son (subject 5)
also reported headaches, decreased concentration, and
decreased memory. The 1-yr-old son (subject 6) had
erythema, a skin rash, and lacrimatory conjunctivitis.
The recurrent rashes on the face and body were the
most bothersome.
The family returned for a second visit in August
2002. The history and examination were supplemented
with a neurological test battery (Table 7). Subject 1
Dahlgren et al.
reported continuing symptoms of decreased concentra-
tion and short-term memory. Objective testing revealed
abnormally prolonged choice reaction time. The
neuropsychological tests revealed cognitive disorder,
psychomotor and functioning impairment, and evidence
of a clinical diagnosis of toxic encephalopathy.
Patient 2 had continuing symptoms of blurred
vision, rhinitis, headache, insomnia, lack of concentra-
tion, decreased short-term memory, driving confusion,
and mood swings. The neuropsychological tests re-
vealed cognitive disorder, and psychomotor and func-
tional impairment.
Subject 3, now 14 yrs old, experienced a complex
partial seizure in March 2002. Extensive work-up has
failed to reveal any anatomic cause of the seizure. She
has delayed menarche; her breasts stopped developing
after the exposure. She also has delayed bone growth.
A bone x-ray diagnostic detected a bone age delay of
nearly 4 yrs. The patient who was always an A student
previously now finds school work difficult. Neurolog-
ical testing revealed abnormal color vision, prolonged
sway speed, and prolonged Trails A and B times. The
neuropsychological tests revealed cognitive disorder,
word-finding anomia, left-sided auditory imperception,
proactive interference in verbal learning, and relative
weakness in visual discrimination of complex stimuli.
Subject 4, now 11 yrs old, reported continuing
symptoms of headaches, decreased memory, mood
swings, and skin rash. Neurological testing revealed
abnormal color discrimination, prolonged simple reac-
tion and choice reaction times, prolonged sway speed,
prolonged pegboard time, prolonged Trails A and B
times, and abnormal perimetry. The neuropsychological
tests revealed cognitive disorder, oromotor-sequencing
dysfunction, word-finding anomia, left-sided auditory
imperception, and mild astereognosis.
Subject 5, now 9 yrs old, has continuing symptoms
of headaches. He developed a pathological fracture in a
unicameral bone cyst in his left femur. He has undergone
curettage and marrow grafting of his left proximal
femoral unicameral bone cyst on five occasions. The
orthopedist performing the surgery has noted that subject
5 has not followed a typical pattern in bone healing. The
bone grafts do not heal and calcify together in a normal
fashion. Usually unicameral bone cyst fractures require
only one or at most two attempts to achieve a satisfactory
repair. Neurological testing revealed abnormal color
discrimination, prolonged simple and choice reaction
times, prolonged sway speed, prolonged pegboard time,
prolonged Trails A and B times, and abnormal right eye
perimetry. The neuropsychological tests revealed cogni-
tive disorder, psychomotor and sensorimotor functioning
impairment, and oromotor sequencing dysfunction.
 Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14
For personal use only.

Table 4. Acute symptoms – June 1999.

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7

CNS Severe headaches, Nausea, dizziness, Acute severe Acute headaches Headaches, decreased Severe headaches, NA
Health Effects of Diazinon on a Family

fatigue, insomnia, headaches, sweating, headaches concentration, head congestion

decreased short-term insomnia, lack of decreased memory
memory concentration,
decreased short-term
memory, mood swings,
depression
Muscular- Muscle pain Deep tendon reflexes Left great toe nail NA
skeletal decreased fell off
Respiratory Rhinitis, Rhinitis, lacrimation, Nasal mucosa is Rhinitis, lacrimatory NA
lacrimation shortness of breath, boggy conjunctivitis, upper
coughing, wheezing respiratory infection
GI Vomiting Vomiting Diarrhea NA
Eyes Conjunctivitis Eye and eyelid NA
irritation
Skin Burning sensation Burning sensation on Burning sensation Burning sensation Burning sensation Painful erythema NA
on exposed skin exposed skin on exposed on exposed skin, on exposed skin
skin, rash intermittent mild
erythema

*NA—Not Available.
585
 Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14
For personal use only.

586

Table 5. Chronic symptoms (clinical evaluation)—August 2002.

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7

CNS Decreased Blurred vision, Complex Headaches, Severe headaches Personality changes Possible seizure
concentration, headaches, lack of partial seizure, decreased memory,
decreased short concentration, episode of numbness mood swings
term memory, decreased on right hand and
blurred vision short-term memory, face, fainting spell,
mood swings headaches
Muscular- Delayed bone growth Cyst growths, Delayed Delayed bone
skeletal delayed bone ossification growth, weak
growth of carpal bones tone of oral
musculature
Respiratory Chronic bronchitis
Eyes Eye irritation, Incomplete
conjunctivitis, tear duct, constant
blockage of right lacrimation
lower tear duct
Skin Persistent
erythematory
pinpoint macules
Dahlgren et al.
 Health Effects of Diazinon on a Family 587

Table 6. Neuropsychological examination and testing results.

Diagnosis Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7

Cognitive disorder X X X X X X X
Psychomotor and sensorimotor X X X X
functioning impairment
Toxic encephalopathy X X X X X X X
Oromotor sequencing dysfunction X X X X
Attention/executive dysfunction X X X X X
Word finding anomia X X X
Auditory imperception X X X
Mild astereognosis X X X
Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14

Proactive interference in X X
verbal learning
Relative weakness in visual X
discrimination of complex stimuli
Severe expressive language disorder X
Phonological disorder X
Wide range of mild to severe X X X
cognitive impairments

Subject 6, now 4 yrs old, has continuing symptoms from his mistakes. He also had delays in sensory
For personal use only.

of erythematory pinpoint macules on the skin around
his left eye and white spots on his cheeks where the
red rash occurred with the pesticide exposure. A bone
x-ray revealed selective delayed ossification of the
carpal bones. He did not undergo neurological testing
due to his age. The neuropsychological tests revealed
cognitive disorder, oromotor sequencing dysfunction,
and attention/executive dysfunction.
Subject 7, the son exposed in utero at 21 weeks
gestation, at 2 yrs of age experienced soreness under
his eyes and was found to have an incomplete tear
duct. Review of his medical records indicates that his
treating physician states he may have had a seizure.
The child’s parents reported that he behaves in
ways that injure himself and others such as head
banging, biting, and scratching and was not learning
processing, primarily proprioception, which affects his
stability and grasp, and was silent and slow to mouth
words (speak). He did not undergo neurological testing
due to his age.
At 23 months of age the Regional Center identified
the patient as having a severe expressive communica-
tion developmental disability. At 36 months of age
neuopsychological tests identified a severe expressive
language disorder (dysphasia), an oromotor sequencing
disorder (oromotor dyspraxia), a phonological (articu-
lation) disorder, and a wide range of mild cognitive
impairments. Some of the neuopsychological testing
results are explained in the discussion. The neuo-
psychologist diagnosed the patient as having a
cognitive disorder due to toxic encephalopathy includ-
ing an expressive language disorder (congenitally

Table 7. Percent predicted values for family.

Initial CNS testing

Color vision Reaction time Balance test Pegboard test Trails

Patient
name Score Simple Choice Eyes open Eyes closed Right peg Left peg Parts A Part B

Patient 1 89 106 130 100 115 94 94 116 106

Patient 2 115 117 91 70 84 97 100 99 83
Patient 3 132 111 103 122 119 96 98 120 129
Patient 4 133 135 185 127 117 119 139 131 124
Patient 5 152 192 158 137 133 141 146 119 138
MEAN 124 132 133 111 113 110 115 93 116
 588
acquired type) and a phonological disorder (congeni-
tally acquired type).
Four of the five children have skeletal issues.
Patient 5 has cyst growths in his bones (unicameral
bone cyst and liquid filled cyst). Patient 5 has had five
bone grafts to repair pathological fractures. According
to the ‘‘Atlas of Graulich & Pyle (AGP) (40)’’ the
bone age for Patient 5 is estimated at 9 yrs, plus or
minus 6 months. His chronological age is 10 yrs 1
month. According to the AGP the bone age for Patient
3 is estimated at 10 yrs, plus or minus 3 months. Her
chronological age is 14 yrs and 5 months. The bone
Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14
age for Patient 6 is variable by different parameters. By
metacarpals and phalanges, it is approximately 4 yrs
and 6 months. His chronological age is 4 yrs 11
months. There are only two ossification centers of
carpal bones noted, which is seen at the age of 2 yrs,
after which other centers are ossified. The radiologist’s
impression was that this might be selective delayed
ossification of the carpal bones. According to the AGP
the bone age for Patient 7 is estimated at 2 yrs, plus
or minus 6 months. His chronological age is 3 yrs
1 month.
For personal use only.
DISCUSSION
Three years after diazinon exposure, the patients
continue to have neurologic symptoms. There was
objective evidence of brain dysfunction confirmed by
neurologic testing in all the family members tested
except for the father (Patient 2). Table 7 shows the
percent-predicted neurological values for the family.
The percent predicted values greater than 100%
indicate abnormal values.
In addition to central nervous effects, there were
additional endocrine disrupting, bone dysfunction, and
skin irritating effects in the children. Young children
may be especially at risk for pesticides because of
their normal tendency to explore their environment
orally, combined with their proximity to potentially
contaminated floors, surfaces, and air (22,23). In
addition, physiological characteristics of young chil-
dren, such as high intake of food, water, and air per
unit of body weight, may also be at higher risk for
adverse effects (22).
A few high-quality epidemiological studies have
been able to suggest that acute organophosphate
poisoning can cause long-term neuropsychological
and neurological sequelae. Jamal et al. cites that high
levels of organophosphates suggest neurobehavioral
changes and other neuropsychiatric complaints for up
Dahlgren et al.
to 3 to 4 yrs after initial intoxication (6). Rosenstock
et al. reported CNS symptoms an average of 2 yrs after
a single OP exposure (9). The poisoned group did sig-
nificantly worse on neuropsychological test battery (9).
Steenland et al. reported significant trends of both
peripheral and central nervous system function in more
than one hundred individuals, years after their acute
OP poisoning (24).
The youngest child (Patient 7) exposed in-utero in
the fifth month of gestation was diagnosed by the
neuropsychologist with a congenital brain injury
resulting in a toxic encephalopathy with severe ex-
pressive language disorder involving severe phono-
logical and oromotor impairments. Patient 7’s
neuropsychological testing protocol at 3 yrs of age
following some months of remedial interventions for
his severe expressive language disorder showed that the
patient had a WPPSI-R spoken vocabulary, more than
two standard deviations below the mean with a
prorated IQ estimate standard score equivalent of 64
compared with the patient’s nearly two standard
deviation above the mean score on the Full-Range
Picture Vocabulary Test and a two standard deviation
above the mean score on the WPPSI-R Block Design
Subtest. The Full-Range Picture Vocabulary Test
requires patients to point to one of four pictures that
best defines a word spoken to them. Hence, it is clear
that the patient’s receptive language skills were not
only intact, but in the superior range, while the
patient’s ability to speak was in the well-below
expectation or mentally defective range, demonstrating
clear dysphasia. The block design subtest of the
WPPSI-R is generally considered to be the best single
estimate of nonverbal intelligence and is more
specifically considered to be a good measure of
nonverbal abstract visual-spatial reasoning and organi-
zation ability. Patient 7’s particular combination of
deficits and strengths provides strong evidence that this
patient suffered damage to those components of his
functional neuroanatomy that are essential for spoken
language that were in a crucial stage of development at
the time of the patient’s exposure to the neurotoxin
during the fifth month of gestation.
There were a number of other very interesting
results in Patient 7’s neuropsychological testing
protocol. Patient 7’s score on the NEPSY Block Cons-
truction Subtest was borderline range with an IQ
estimate equivalent standard score of 85, which is one
standard deviation below the mean, a score in strong
contrast to the patient’s score on the WAIS-III Block
Design Subtest. However, there is a crucial difference
between these two tests, The NEPSY Block Construc-
 Health Effects of Diazinon on a Family
tion Subtest requires a three-dimensional construction
with blocks either by copying a three-dimensional
model constructed by the examiner or in response to a
picture that shows a three-dimensional construction that
the patient must construct using blocks. On the other
hand, the WPPSI-R Block Design Subtest requires
the construction of designs in two dimensions. This
particular contrast between two- and three-dimensional
design construction provides evidence that this patient
was also injured during gestation in the development of
certain nonverbal functions required for three-dimen-
sional abstract visual-spatial reasoning, but not for two-
Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14
dimensional abstract visual-spatial reasoning. The
present finding with Patient 7 provides a model for a
double dissociation paradigm (25 –32) in the study of
two-dimensional vs. three-dimensional space percep-
tion and also provides evidence to support the
conclusion that three-dimensional space perception
involves anatomically different areas of the brain that
are not required for two-dimensional space perception.
Finally, the present result with Patient 7 provides
evidence that both the cognitive structures required for
the development of spoken language and for three-
For personal use only.
dimensional spatial reasoning are in critical stages of
development during the fifth month of gestation.
Diazinon has also been causally linked to neuro-
behavioral impairment in the offspring of exposed
mice. Diazinon given throughout gestation revealed
functional impairments in the offspring. Impairments
include significantly slower growth, slower running
speeds and less endurance, impairment of neuromus-
cular strength and/or coordination, and forebrain
damage observable under light microscopy (23). In
summary, the present findings add to the growing body
of evidence showing that diazinon is a very dangerous
chemical that affects gestation and development as well
as adult functioning.
Patient 3’s delayed puberty is a rather unique
outcome. Diazinon has toxicity to the endocrine
system. Animal studies have reported that mice
exposed to diazinon had offspring which showed
significant delays of sexual maturity (descent of testes
or vaginal opening) (23). Another study reported that
the response of in vitro exposure of rainbow trout
showed adrenocortical cells to diazinon significantly
decreased cortisol secretion and cell viability. The level
at which diazinon caused a reduction of cortisol
secretion closely followed the decrease of cell viability,
which the authors attribute to the cytotoxic effect of
diazinon (33). The authors conclude that endocrine
toxicity is almost the same as its cytotoxicity for
diazinon. Bisson et al. also cite a study in which
589
elevated plasma corticosterone levels were reported in
mice exposed to diazinon in-utero or neonatally via
milk (34).
Acetylcholinesterase in bone matrix provides a
possible mechanism for organophosphate-induced
effects in bone. Compston et al. reports that bone
histomorphometric analysis of the transiliac bone in 24
agricultural workers with chronic organophosphate
exposure showed significantly lower bone formation
(35). Cancellous bone area as well as cellular and
tissue indices of bone formation were significantly
lower in samples of the agricultural workers than those
of controls (35). There was a significant increase in
erosion in the peripheral portion of the bones of
agricultural workers vs. control samples (35). The
authors attribute the bone erosion to a failure by
osteoblasts to fill in the reabsorbed cavities, and it was
not due to overactive osteoclasts since few were
present. Acetylcholinesterase is reportedly present in
bone matrix and is expressed by osteoblasts and is
present along cement lines and in osteoid. The
possibility of organophosphate-induced effects in bone
is introduced as acetylcholinesterase may have a role in
cell-matrix regulation and interaction as well as bone
resorption and formation (35).
In a retrospective cohort study by Stephen et al. of
80 sheep farmers with documented high-level chronic
exposure to organophosphates, bone mineral density
was lower than expected (36). The sheep farmers lead
active lives, are well-nourished and are exposed to
sunlight for extended time periods. Forty percent of
sheep farmers were one standard deviation below the
mean adult male reference range for bone mineral
density (BMD) at one or more body site (spine, hip, or
distal radius) and 60% of these subjects were 1.5
standard deviations below the mean adult reference
range for BMD (36). The findings suggest the pos-
sibility of direct action on the skeleton, which may be
due to the sheep farmer’s long-term chronic occupa-
tional exposure to organophosphate insecticides.
Diazinon also has been reported to affect the bird
skeletal system. Birds injected with diazinon caused
malformations of the cartilage and bone and delay of
growth, and the length of the limbs was decreased (37).
Skeletal malformations were also confirmed in quail
embryos (38).
CONCLUSIONS
The present findings strongly indicate that children
are more susceptible than adults to the neurotoxic
 590
effects of diazinon upon their centeral nervous system
development and functioning. In our case study, the
manifestations of acute diazinon poisoning have also
resulted in bone dysfunction, endocrine problems, and
skin irritation, which is consistent with acetylcholines-
terase inhibition studies in the literature. The EPA has
already begun a phase-out program for diazinon (39).
The results of this study support the hypothesis
that acute organophosphate exposure is associated with
neurological sequelae. The permanent sequelae of the
diazinon exposure in the children were neurological
and endocrine. The adults appear to be more resistant
Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14
to the effects of diazinon. The children in our case
study have been affected from this acute exposure
more so than the adults, demonstrating that children are
more susceptible to acute OP exposure.
Residential application of organophosphate pesti-
cides (OP) should be avoided if children or pregnant
females are exposed. We are hopeful that our results
will benefit our understanding how acute OP exposure
affects children.
For personal use only.
REFERENCES
1. Berger AR, Schaumburg HH. Effect of occupa-
tional and environmental agents on the nervous
system. In: Bradley WG, Daroff RB, Fenichel GM,
Marsden CD, eds. Neurology in Clinical Practice.
Vol. 2. 2nd ed. Boston: Butterworth-Heinemann,
1996:1389– 1401.
2. Rom W. Environmental and Occupational Medi-
cine. 2nd ed. Little Brown and Company, 1992.
3. Namba T, Nolte CT, Jackrel J, Grob D. Poisoning
due to organophosphate insecticides. Am J Med
1971; 50:475 –492.
4. Hayes W. Pesticides Studied in Man. Baltimore:
Williams & Wilkins, 1982:385 –389.
5. Hayes W, Laws ER. Handbook of Pesticide
Toxicology. New York: Academic Press, 1991.
6. Jamal GA. Long term neurotoxic effects of
organophosphate compounds Adverse Drug React.
Toxicol Rev 1995; 14(2):85 –99.
7. Keifer M, Mahurin R. Chronic neurological effects
of pesticide overexposure. Occup Med 1997;
12(2):291 –304.
8. Rosenstock L, Daniell W, Barnhart S, Schwartz D,
Demers PA. Chronic neuropsychological sequelae
of occupational exposure to organophosphate
insecticide. Am J Ind Med 1990; 18:321 –325.
9. Rosenstock L, Keifer M, Daniell W, McConnell R,
Claypoole K. Chronic central nervous effects of
Dahlgren et al.
acute organophosphate pesticide intoxication. Lan-
cet 1991; 338(8761):223 –226.
10. Savage E, Keefe T, Mounce L, Heaton R, Lewis J,
Burcar P. Chronic neurological sequelae of acute
organophosphate pesticide poisoning. Arch Envi-
ron Health 1988; 43(1):38 –45.
11. Kilburn KH, Thornton JC, Hanscom B. Population
based prediction equations for neurobehavioral
tests. Arch Environ Health 1998; 53(4):257 – 263.
12. Kilburn KH, Warshaw RH, Hanscom B. Balance
measured by head (and trunk) tracking and a force
platform in chemically (PCB and TCE) exposed
and referent subjects. Occup Environ Med 1994;
51:381 – 385.
13. Miller J, Cohen G, Warshaw R, Thornton J,
Kilburn KH. Choice (CRT) and simple reaction
times (SRT) in laboratory technicians: factors
influencing reaction times and a predictive model.
Am J Ind Med 1989; 15:687 – 697.
14. Klove H. Clinical neuropsychology. In: Forester
FM, ed. The Medical Clinics of North America.
New York: Saunders, 1963.
15. Mathews CG, Klove H. Neuropsychological Test
Battery Manual. Madison, WI: University of
Wisconsin, 1964.
16. Lezak M. Neuropsychological Assessment. 3rd ed.
New York: Oxford University Press, 1995.
17. Lanthony P. The desaturated panel D-15. Doc
Ophthalmol 1978; 46:185 – 189.
18. Bowman KJ. A method for quantitative scoring of
the Farnsworth Panel D-15. Acta Ophthalmologica
1982; 60:907 –916.
19. Reitan RM. Validity of the trail-making test as an
indicator of organic brain damage. Pecept Motor
Skills 1958; 8:271 – 276.
20. Johnson CA, Samuels SJ. Screening for glau-
comatous visual field loss with frequency-dou-
bling perimetry. Invest Ophthalmol Vis Sci 1997;
38(2):413 – 425.
21. Currie KL, McDonald EC, Chung LTK, Higgs AR.
Concentrations of diazinon, chlorpyrifos, and ben-
diocarb after application in offices. Am Ind Hyg
Assoc J 1990; 51(1):23 – 27.
22. Eskenazi B, Bradman A, Castorina R. Exposures
of children to organophosphate pesticide and thier
potential adverse health effects. Environ Health
Perspect 1999; 107(3):409 –419.
23. Spyker J, Avery D. Neurobehavioral effects of
prenatal exposure to the organophosphate diazinon
in mice. J Toxicol Environ Health 1977; 3:989 –
1002.
24. Fant ME, Harbison RD, Harrison RW. Glucocor-
 Health Effects of Diazinon on a Family
ticoid uptake into human placental membrane
vesicles. J Biol Chem 1979; 254:6218 – 6221.
25. Russell EW. The cognitive-metric fixed battery
approach to neuropsychological assessment. In:
Vanderploeg RD, ed. Clinician’s Guide to Neuro-
psychological Assessment. Hillsdale, NY: Erl-
baum, 1994:211– 258.
26. Russell EW. The cognitive-metric, fixed battery
approach to neuropsychological assessment. In:
Clinician’s Guide to Neuropsychological Assess-
ment. 2nd ed. Mahwah, NJ: Erlbaum, 2000:449 –
481.
Clinical Toxicology Downloaded from informahealthcare.com by University of Washington on 10/28/14
27. Shallice T. Case study approach in neuropsycho-
logical research. J Clin Neurophysiol 1979;
1:183 –211.
28. Shallice T. Neuropsychology to Mental Structure.
Cambridge: Cambridge University Press, 1988.
29. Teuber H-L. Physiological psychology. Annu Rev
Physiol 1955; 6:267 –296.
30. Teuber H-L. Recovery of function after brain
injury in man. In: Ciba Foundation Symposium 34
(new series), Outcome of Severe Damage to the
Central Nervous System. Vol. 34. Amsterdam:
For personal use only.
Elsevier, 1975:159– 190.
31. Walsh K, Darby D. Neuropsychology: A Clinical
Approach. 4th ed. Edinburgh: Churchill Living-
stone, 1999.
32. Webster JS, McCaffrey R, Scott RR. Single case
design for neuropsychology. In: Wedding D,
Horton AM, Webster J, eds. The Neuropsychol-
ogy Handbook: Behavioral and Clinical Perspec-
tives. New York: Springer, 1986:219 –258.
33. Bisson M, Hontela A. Cytotoxic and endocrine-
disrupting potential of atrazine, diazinon, endosul-
591
fan, and mancozeb in adrenocortical steroidogenic
cells of rainbow trout exposed in vitro. Toxicol
Appl Pharmacol 2002; 180(2):110 –117.
34. Cranmer JS, Avery DL, Grady RR. Postnatal
endocrine dysfunction resulting from prenatal
exposure to carbofuran, diazinon, or chlordane. J
Environ Pathol Toxicol Oncol 1978; 2:357 –369.
35. Compston JE, Vedi S, Stephen AB, Bord S, Lyons
AR, Hodges SJ, Scammell BE. Bone histomor-
phometric analysis in 24 agricultural workers with
chronic organophosphate exposure showed signif-
icantly lower bone formation at tissue and cellular
level than in healthy controls. Lancet 1999;
354:1791 – 1792.
36. Stephen A, Lyons A, Scammell B, Miller C,
Hodges. Idiopathic osteoporosis in sheep farming
men in the UK: skeletal poisoning by organophos-
phate insecticide. J Bone Miner Res 1998;
23:S395.
37. Misawa M, Doull J, Kitos P, Uyeki E. Teratogenic
effects of cholinergic insecticides in chick embry-
os. III. Development of cartilage and bone. J
Toxicol Environ Health 1982; 10:551 – 563.
38. Meneely G, Wyttenbach C. Effects of OP in-
secticides diazinon and parathion on bobwhite
quail embryos: skeletal defects and acetycholines-
terase activity. J Exp Zool 1989; 252:6 –70.
39. EPA. Questions and Answers: Diazinon Revised
Risk Assessment and Risk Mitigation Measures.
Prevention, Pesticides and Toxic Substances,
2000, (7506C).
40. Greulich WW, Pyle SI. Radiographic Atlas of Skel-
etal Development of the Hand and Wrist. 2nd ed.
Stanford, CA: Stanford University Press, 1959.