Jpn J Clin Ecol（Vol.23 No.1 2014）14「第22回日本臨床環境医学会学術集会特集」
Review

Symposium

Human neonicotinoids exposure in Japan
Kumiko Taira
Department of Anesthesiology, Tokyo Women’s Medical University Medical Center East

Abstract
In Japan, there are currently seven neonicotinoid (NN) insecticides, e.g. acetemiprid, since 1992 registration of
imidacloprid. The amount of domestic shipment of NNs was 407t in 2009. NNs are water-soluble, systemic, nonvolatile and thermostable. Japanese MRLs for NNs are set at high levels compared to the rest of the world. NNs
show persistent efficacy in plants, soil and natural water. Once ingested, NNs are transported through intestinal
mucosa, blood-brain-barrier and placenta.
The suspected health effects of environmental exposure to NNs were observed in Japan.
1.	Inhalational exposure: 78 patients in 2004 and 63 patients in 2005 visited a clinic in Gunma prefecture with headache, chest pain and muscle pain after acetamiprid spray application to pinewoods for a few weeks.
2.	Oral exposure: Since 2006, more than 4,000 patients visited the clinic after consecutive intake of conventional
produce, e.g. domestic fruits/vegetables 500 g/day and/or tea beverage 500 mℓ/day, with health problems (neoConventional Produce Syndrome, neo-CPS). Urinary 6-chloronicotinic acid (a common metabolite of four NNs)
was quantified by liquid chromatography/mass spectrometry at 7.5-84.8 ng/mℓfrom 6 neo-CPS patients with
finger tremor, impaired short-term memory, fever, general fatigue, headache, palpitation/chest pain, abdominal
pain, muscle pain/muscle weaknes/muscle spasm, and cough (neo-nicotinic symptoms), as well as abnormal
electrocardiogram.
	From the urine of 2 neo-CPS patients with neo-nicotinic symptoms, acetamiprid and seven NN metabolites werequalitatively detected by liquid chromatography/time-of-flight mass spectrometry; and urinary N-desmethylacetamiprid (a unique metabolite of acetamiprid) was quantified by liquid chromatography/tandem mass spectrometry at 3.2 ng/mℓfrom one of them.
( Jpn J Clin Ecol 23 : 14－24, 2014)《Key words》neonicotinoid, insecticide, acetemiprid, imidacloprid, intoxication

Ⅰ. Introduction

honeybee population1). In Japan, no valid survey system

Neonicotinoid (NN) is a systemic insecticide thatexists to watch the number of pollinators; however,possesses nicotinic action as an α4β2 nicotinic

there are some reports of the decline of the honeybee

acetylcholine receptor agonist; and its usage ispopulation2).

increasing in the world. The EU decided to ban three

We have been studying the environmental health

NN insecticides for two years starting in 2013

effects of NN in Gunma prefecture in Japan for ten

because of their concern about the decline of theyears3). In 2013, a metabolite of NN was quantified

Reprint Requests to Kumiko Taira, Department of Anesthesiology, Tokyo Women’s Medical University Medical Centre East, 2-1-10 Nishiogu, Arakawa, Tokyo
116-8567, Japan

Human neonicotinoids exposure in Japan

from the urine of patients, who were suspected of
4)environmental NN intoxication .

15

The shipment of NN in Japan has been increasing.

Environmental

In 1992, imidacloprid was registered first, followed byexposure to NN may lead to typical cardiovascularacetamiprid. In 2012, non-chlorinated NN, dinotefuran,and nervous symptoms, which are distinct from those

was the most shipped, followed by imidacloprid,caused by organophosphates (OPs), in addition to theclothianidin, and acetemiprid (Figure 2). NNs are usedadverse effects on pollinators.

in various situations, e.g. agriculture, home gardening,

In this review, “what neonicotinoids are” is discussed

forestry, lawn, termite extermination, building-first, followed by “case presentation of environmental

products, drugs for animal and disinfectants . In theneonicotinoid exposure” and finally “why neonicotinoid

last ten years, the total shipment of NN insecticides

intoxication was observed in Japan”.

increased more than two-fold, while that of OP

7)

insecticides reduced by half to approximately 3,000t,

Ⅱ．What are neonicotinoids?

which is comparable to 400t of NNs. NN insecticides

As of 2014, seven NNs are commercially available
inJapan,

namely,imidacloprid,

are more potent than OP insecticides by weight7).

acetamiprid,

The characteristics of three classes of insecticides

nitenpyram, thiacloprid, clothianidin, thiamethoxam

are summarized in Table18－12). Acetamiprid represents

and dinotefuran (Figure 1). Six out of seven of the

NN; MEP (Fenitrothion) represents OP; and DDT

NNs possess the same characteristics as chlorinatedrepresents OC insecticides. NN is water-soluble andorganic compounds. Chlorinated organic compounds

systemic. It penetrates into the plant body and exerts

are characterized by their strong and prolonged

its effects. NN cannot be removed from fruits andaction, for example organochlorine (OC) insecticide,vegetables even by washing them with soap water.

including DDT. Recently, two novel insecticides withNN has a very low volatility. However, NN could benicotinic action, cycloxaprid and sulfoxaflor, aredisseminated by contaminating in particle matter .

5, 6)
registered in foreign countries .

NN is long-lasting in efficacy. The efficacy of NN, of

Figure 1

13)

Chemical structures of neonicotinoid insecticides.

Jpn J Clin Ecol（Vol.23 No.1 2014）

16

500

Annual Shipment (ton)400

dinotefuran
300

clothianidin
200

thiamethoxam

nitenpyram

thiacloprid

acetamipirid
100

imidacloprid

11

10

20

09

20

08

20

07

20

06

20

05

20

04

20

03

20

02

20

01

20

00

20

99

20

98

19

97

19

96

19

95

19

94

19

93

19

19

19

92

0

Fiscal YearFrom Oct. of the previous year ll Sept. of the year
Figure 2

The shipment of neonicotinoids in Japan.

(Source: Webkis-plus 29), Center for Environmental Risk Research, National Institute for Environmental Study)

Table 1

Characteristics of three classes of insecticidesClass(Abbreviation)
For example
Water solubility
log Pow (20 °C)
Volatility
Vapor pressure (Pa)
Efficacy period
Half life in water
Bio-concentration
Log BCF
Bio-accumulation
Environmental accumulation
Toxicity for mammals
LD50 (rat♂, mg/kg BW）
Neurodevelopmental toxicity

Neonicotinoid(NN)

Organophosphate(OP)

Organochlorine(OC)

Acetamiprid
High
0.8
Very low<1.0x10-6 *1
Long
349 days *4−
2
Possible
Possible

MEP
Low
3.43
Medium1.57x10−3 *2
Short
57days *5−
1.3-2.6−−

DDT
Very low
6.76
Low
2.53x10−5 *3
Very long
150 years+
2.7-4.9++217
Suspected

945
Suspected

113
Suspected*1: 25 °C, *2: 25 °C, *3: 20 °C, *4: natural water, *5: pH 7.1, 30 °C,
Reference: 8-12)

Human neonicotinoids exposure in Japan17

course, is not as long as OC, but longer than OP. For

to a height of 40 m or higher above the ground during

example, the half-life of acetamiprid in natural water

several weeks. Seventy-eight patients visited a clinic

is about one year. In soil, more than 3 months are

in Gunma prefecture 0.5-3 days after the applicationneeded for an 80% decline of acetamiprid and its

with symptoms of central nervous system 91%

9)metabolite , so environmental accumulation of NN
14)

may occur . Bio-concentration factors of NNs are
10, 12)(headache, general fatigue, depression, impairment ofconcentration, sleep disorders, memory impairment,

because of its high water-or fretfulness and difficulty in speech), skeletal muscle

solubility and low octanol-water partition coefficient.

91% (shoulder stiffness, muscle weakness/muscle

Meanwhile how much bioaccumulation of NNs occurs

spasms/muscle pain or tremor), cardiovascular system

in human body is not known.

77% (chest pain or palpitations), body temperature

lower than DDT

77% (fever or coldness of extremities), eye 67.9%

Ⅲ．Environmental neonicotinoid exposureand health effect(accommodation disorder, photophobia or reducedⅰ. Subacuteelectrocardiographic

pain, diarrhea or constipation), respiratory systemfindings observed after acetamiprid spray ap-

42.3% (cough or sputum), secretory gland 30.8%

plication for pinewoods(sweating,abnormalvisual acuity), gastrointestinal tract 60% (abdominal

salivationorthirst/dry

mouth)

andGunma prefecture is located in the middle of Japan.

electrocardiographic abnormalities 89% (ST-T changes

Two million people live in this 700 km basin, at the

68%, bradycardia, tachycardia, T-wave abnormality orhead of the Tone River.

prolonged QT intervals) . Their demographic data are

2

7)

In the summer of 2004, acetamiprid was sprayed forpinewoods as a countermeasure against pine wilt

shown in Table 2. During this season, OP (mainly DEP
and MEP) was also applied a little.

disease. A 0.02% acetamiprid aqueous solution was

The following year, acetamiprid was applied again; andapplied on pinewood forests in the mountainsides withsixty-three patients visited the clinic with chest pain,

air blast spraying equipment, which blew the solution

chest discomfort or palpitations with headache, nausea

Table 2

Demographic data and electrocardiographic findings of patients
after the acetemiprid ground application

Year

2004

2005

Applied pesticide
Applied period
Total spread volume (t)Total applied acetamiprid (kg)acetamiprid per area (μg/m2)

Acetamiprid (+OP)
5.26-6.28
249
49
70

Acetamiprid
5.17-6.24
158
31.6
45

Number of patientsmale/female
Age (years old)under 15 years old
Abnormal Electrocardiogram (%)
Sinus tachycardia
Sinus bradycardia
ST-T changes
T-wave abnormality
Prolonged QT intervals

78
20/58
2-62
32 (50%)69 (89%)7 ( 9%)
25 (32%)53 (68%)16 (21%)7 ( 9%)

63
18/45
3-78
15 (26%)57 (91%)14 (22%)4 ( 6%)
30 (49%)7 (11%)
12 (19%)Jpn J Clin Ecol（Vol.23 No.1 2014）18

Table 3

Acetamiprid deposits during and after the ground application

Sampling point

Distance from thesprayed area (km)Maximum Deposit(ng/cm2)

Interval after
application (hours)

0
0.5
2
3
5

311.7
11.2
1.31
2.32
2.25

During application
During application
6-8
During application
6-8

Ⅰ
Ⅱ
Ⅲ
Ⅳ
Ⅴ
Reference: 15)

and dizziness7). Electrocardiographic abnormality wasabnormal heart rhythm (tachycardia, bradycardia andfound in 91% patients (ST-T change, tachycardia, QT

arrhythmia) were observed clinically. The patients’prolongation, bradycardia) (Table 2).

ages ranged from 1 to 79 years old. All patients were

In 2005, a research group quantified acetamiprid

non-smokers.

It is noteworthy that acetemiprid

deposits after the ground application. The maximum

spray application for pinewoods ceased by July 2006

values of deposits in the applied area were higher

in Gunma. Five hundred forty nine out of 1,111 of thethan those in non-applied area; however, low-level

patients had consumed large amounts of conventionallydeposits were also found at 2-5 km away from thegrown domestic fruits/ vegetables or tea beverages

applied area. The maximum values of deposits were

before the onset. All were recovered by prohibition ofsometimes observed 6-8 hours after the application

domestic fruits and tea beverage .

15)

7)

We therefores symptoms were caused(Table 3) . If the patient’referred to these new symptoms as neo-Conventionalby acetamiprid, the maximum dose of exposure is

Produce Syndrome (neo-CPS), which follows theestimated to be 84.1μg/kg BW.

intake of conventional produce. From 2007 to 2009,

In literature, a few cases of occupational inhala­no less than 4,000 patients visited the clinic with neo-tional exposure to NN insecticides were reported. In

CPS, and 193 were from outside of Gunma, e.g.

acute inhalational exposure, imidacloprid caused

Saitama, Tochigi, Tokyo, Kanagawa, Ibaragi, Chiba,severe systemic action, e.g. renal and hepatic

Nagano, Niigata, Yamanashi, Shizuoka, Aichi, Miyagi,

dysfunctions, leukoclastic vasculitis, rhabdomyolysis,

Iwate, Osaka and Shimane.

16, 17); and in chronic inhalational

We speculated neo-CPS might be mainly caused byexposure, NN was related to a decrease in lungoral NN exposure, although exposure to otherfor more than a week
18)

capacity . Inhalational exposure to NN may induce a

pesticides, phytochemicals and other environmental

delayed reaction, which is consistent with the animal

pollutants has not been excluded.

studies19, 20).

ⅱ. Subacute intoxication after consecutive intake of fruits and tea beverages

Neo-CPS was

em­
piri­
cally defined as the symptoms of unknown
origin after consecutive intake of domestic fruits/
vegetables 500g/day or tea beverage 500mℓ/day for

Since August 2006, 1,111 patients visited the clinic

more than several days. We began to collect neo-CPS

in eight months with chest pain, chest discomfort orpatients’ urine for chemical analysis of NN metabolites.

palpitations, which resembled to those found afterFirstly, we sought to analyze 6-chloronicotinic acidacetemiprid spray application. They also complained(6-CNA) as a urinary biomarker by ion chromatographyof headache, abdominal pain, muscle pain and fever.

with the lowest level of qualification (LOQ) of 40 ppb.

Impaired short-term memory, finger tremor, and

6-CNA is a common metabolite of chloropyridinyl

Human neonicotinoids exposure in Japan

neonicotinoid i.e. acetamiprid, imidacloprid, thiacloprid,19

4)

N- (6-chloronicotinoyl)-glycine (Figure 3).

nitenpyram21) and cycloxaprid (Figure 3). Urine was

Finally, we quantified N-desmethyl-acetamiprid at

prospectively collected from thirty-three patients with

3.2 ppb with LOQ of 0.5 ppb, and acetemiprid at 0.058

neo-CPS. They were classified into two groups by

ppb (less than LOQ of 0.1 ppb) by liquid chromatography/

the onset time, Group A: eleven patients who visited

tandem mass spectrometry in the urine of a neo-CPS

the clinic within 24 hours after the onset, Group B:

patient with neo-nicotinic symptoms. N-desmethyl-

twenty-two patients who visited the clinic one toacetamiprid was quantified no more than LOQ fromseveral days after the onset or whose onset time waseleven patients without neo-nicotinic symptoms .

not identified.

In Group B, urinary 6-CNA was

From the urine of three 60s-70s women of neo-CPS

detected from only one patient. In Group A, urinary

without abnormal ECG, who were diagnosed

6-CNA was detected from six of eleven patients who

dementia by low value of Hasegawa Dementia Scale

showed similar symptoms and mainly took domestic(<20) with impaired short-term memory, 0.91-1.7

fruits or tea beverage before the onset

21)(Figure 4).

We thought those symptoms were one of the core4)

ppb of N-desmethyl-acetamiprid was quantified(unpublished data).

group of neo-CPS which related to chloropyridinyl

We speculate that neo-nicotinic symptoms isneonicotinoid exposure, and named them neo-

related to the accumulation of NN in the human body,

nicotinic symptoms, i.e. finger tremor, impaired
short-term memory, fever (>37℃), general fatigue,headache, palpitation/chest pain, abdominal pain,
muscle pain/muscle weakness/muscle spasm, andcough.
Secondly, we quantified urinary 6-CNA from neo-CPS
patients with neo-nicotinic symptoms by liquid
chromatography/mass spectrometry with LOQ of 1 ppb.
The levels of urinary 6-CNA ranged from 7.5 to 84.8
ppb. Interestingly in five of six cases, the maximum
level of 6-CNA of each patient’s urine was detected21)

2-20 days after the first visit .
Thirdly, we analyzed the known metabolites ofacetemiprid, imidacloprid and clothianidin by liquid
chromatography/time-of-flight mass spectrometry in
the urine of three neo-CPS patients with neo-nicotinic
symptoms within 24 hours from onset.

NN andmetabolites were qualitatively found from two of themas follows: acetemiprid; an acetamiprid metabolite,
N-desmethyl-acetamiprid; three imidacloprid metabo­lites, 5-hydroxy-imidacloprid, 4,5-dehydro-imidacloprid
and

4,5-dihydroxy-imidacloprid;metabo­lites,twoclothianidin

N-desmethyl-clothianidin,

N-(2-(methylsulfinyl) thiazole-5-carboxyl)-glycine; and acommon metabolite of acetemiprid and imidacloprid,

Figure 3

 etabolic transformation of acetM
emiprid, imidacloprid, clothianidin
and selected metabolites.

Jpn J Clin Ecol（Vol.23 No.1 2014）20

Figure 4

Comparison of subjective symptoms, clinical findings and fruits/vegetables/tea beverage intake between three groups of neo-CPS.

especially acetamiprid. Although it remains unknown

Her performance improved gradually; and her grades

whether NNs, as well as metabolites, are causative

were at the top of her class again (unpublished data).

toxicants or coincidental xenobiotics, we foundFinger tremor is another typical symptom of neo-

retrospectively 102 patients (male/female=20/82)

CPS. Neurologically, it is postural tremor of approxi­

with neo-nicotinic symptoms from 2008 to 2012, allmately 4-12 Hz, and may be diagnosed as an idiopathic

were neo-CPS, and recovered by stopping the intake

one. As the diagnosis of essential tremor of non-of domestic fruits and tea beverage.

smoker, not only caffeine but also the intake of

The reversibility of impaired short-term memory
is one of the most representative symptoms of neo-conventional produces might be considered for
exclusion.

CPS. In October 2006, a 14-year-old girl visited theCharacteristic electrophysiological abnormalities

clinic with headache, shoulder pain, palpitations,are observed in neo-CPS patients. A 28-year-old

impaired short-term memory, insomnia and a poor

woman visited the clinic with chest pain, headache,result of examination. Her grades at school were

sleepiness, constipation, throat pain, and muscle pain

getting worse. She descended from the top of her

after consecutive intake of bottled green tea 500 mℓclass to the bottom in a few months. She could not

per day for more than 3 months. Finger tremor andremember what she ate the previous day.

In

impaired short-term memory were also observed. In

November 2006, she visited an ophthalmologist, andher ECG, severe sinus tachycardia (146 bpm) was

was diagnosed with accommodation disorder sus­

observed on the first day of visit. On the next day,pected by pesticide exposure. In January 2007, her

her heart rate returned to almost the normal range,headache continued. The doctor stopped her intake

but mild QT prolongation emerged.

of fruits and tea beverages. One week later, herfollowed by bradycardia is popular in the patients

headache disappeared; and her impaired short-termwith neo-nicotinic symptoms, as well as intermittent

memory and disorder of accommodation improved.

WPW syndrome, paroxysmal atrial fibrillation or

Tachycardia

Human neonicotinoids exposure in Japan21

early repolarization, which is a candidate trigger of

neo-CPS. A 31-year-old man drank bottled green tea

sudden death. NN might facilitate those kinds of

500mℓ per day consecutively. Since he had prolonged

arrhythmia by the substantial electrocardiographic

exposure to imidacloprid by the termite control of his

condition. In auditory brain stem response (ABR),

dwelling in 2003, he was depressive. A psychiatricthe shortening of the interval between the first wave

doctor administered antipsychotic drugs in diagnosis

and the fifth wave (I-V interval) is a typical finding.

of depression with personality disorder. One day, he

By sound stimulation to the ear, five waves may occur

visited the clinic and complained of muscle pain,by the successive nerve excitation. It is known that

finger tremor, general fatigue, impaired short-termin chronic OP intoxication the fifth wave latency andmemory, insomnia, poor verbal communication,

I-V interval are elongated, but in neo-CPS with neo-

palpitations, chest pain, and fever 38.5 °C. His ECG

nicotinic symptoms, both shorten. In the infrared

showed early repolarization pattern.

pupillography, not only sympathotonic but also

brainstem response, I-V interval was shortened,parasympathotonic findings were observed. A pupil

andaction for photo-stimulation is a good marker ofparasympathotonic pattern. After six weeks of theautonomic activity. Her heart rate was 146 bpm, which

prohibition of green tea, his verbal communicationsuggests sympathotonic. However, the parameter of

improved; and the irritation diminished .

infrared pupillography, D1 and A1 decreased, which

ⅲ. Toxicological consideration of neo-Conven-means miosis; and it can be interpreted as

pupillography

showedIn auditory

sympathotonic

and

22)

tional Produce Syndrome

parasympathetic dominant state. Input disturbance

Minimum levels of urinary NNs and metabolites in

22)

is unlikely. Maxi­mum dilatation velocity increased .

neo-CPS are as follows: N-desmethyl-acetamiprid:

Attention deficit hyperactivity disorder (ADHD)-

3.2 ppb in neo-nicotinic symptoms and 0.91 ppb inlike reactions were observed in a few children of neo-dementia; acetamiprid: 0.058 ppb (<LOQ) in neo-

CPS. A 3-year-old boy went for grape picking with

nicotinic symptoms. In the literature, the minimum

his parents. From Sep 4th, he started drinking fresh

toxic dose of acute acetemiprid intoxication was

grape juice more than 500 mℓ per day. On Sep 8th, herather high (30 mg/kg BW) with plasma acetemiprid

showed incontinence, stomachache and low activity;

7)of 2.39 ppm . However, 3 ppb of imidacloprid wasand his heart rate was 108 bpm. On Sep 11th, he was

detected from the urine of a patient who attempted

hyperactive and unruly; and his heart rate was 85

suicide by ingestion of imidacloprid solution and was

bpm. On Sep 16 , he recovered completely, and his

put in intensive care25).

th

ADHD-like action diminished (unpublished data).
We could not analyze his urine.

neo-nicotinic symptoms seems to occur by the
mediation of nicotinic receptors, because heart,

Skin eruption was frequently observed in neo-CPS

central nervous systems, neuromuscular junction,

20)

who classified in Group B . Anti-virus drug were

gastrointestinal tract, keratinocyte and immune

effective for the skin eruption. In Japan, the pandemic

system have nicotinic acetylcholine receptors. The

of Kaposi’s varicellimorm eruption, which is caused

symptoms developed systemically after the onset

by Herpes Simplex virus, was reported23).

and diminished slowly by prohibition of conventionalThe

immunotoxicity of NNs would be considered for

produce.

human being after chronic exposure. Di Prisco reported

occur in humans by consecu­
tive intake of NNs

that clothianidin acts as a negative modulator of NF-

contaminated food, because bioaccumulation ofκΒ activation in honey bees .

imidacloprid by low dose exposure was observed in

24)

Depression was also observed in a patient of

Bioaccumulation of NN metabolite may

26)

animal study .

Jpn J Clin Ecol（Vol.23 No.1 2014）

22

Table 4
ApplesMRLs for apples and tea-leaves

Japan

US

CODEX

EU

Imidacloprid
Acetamiprid
Thiacloprid
Thiamethoxam
Clothianidin
Nitenpyram
Dinotefuran

0.5
2
2
0.3
1
0.5
0.5

0.5
1
0.3
0.2
0.5

0.5
0.7
0.3
0.5

0.5
0.7
0.3
0.3
0.5
0.01*
0.01*

Tea-leaves

Japan

US

CODEX

EU

Imidacloprid
Acetamiprid
Thiacloprid
Thiamethoxam
Clothianidin
Nitenpyram
Dinotefuran

10
30
30
20
50
10
25

－
50**

－
－
－
20
0.7
－
－

0.05*
0.1*
10
20
0.7
－
－

－
20***
70****－－* indicates lower limit of analytical determination.
**There are no U.S. registrations as of February 10, 2010, for the use of acetamiprid on dried tea-leaves.
***There are no U.S. registrations as of March 27, 2013.
****No U.S. registrations.

In our study, women seem to be more susceptible than4, 7, 21)

toxicities of NNs are comparable to those of OPs, and. Because both cytochrome P-450 enzymes andlethal (Table 1). We have not been aware of the highaldehyde oxidases are active for NN metabolism inresidual pesticides for the decades before 1992 when

the human body, they may develop some metabolites

the use of NNs started. Successive use of NNs may

whose toxicities are not comprehensively evaluated;cause accumulation and toxicity in the environment

and the diversity of those enzyme activities by

and human beings. We should use NN insecticides

species, polymorphism and estrogen-like substances

restrainedly and rationally.

men

are known

ⅱ. Vicinity of applied area from residence

27－29).

As the cause of neo-CPS, other pesticides, phyto­

Many farms and forests in Japan are located nearchemicals and new environmental pollutants must be

residential areas. When NN insecticide is applied byconsidered, in addition to nine neonicotinoids. Further

aerial or ground spraying, residents are vulnerable toinvestigation is needed.

exposure to drift. The information of spray driftcaused by NN application should be properly obtained

Ⅳ. Why neonicotinoid intoxication occurs
in Japan?
ⅰ. Poor understanding of characteristics

and needs to be disclosed to the public.
ⅲ. High MRLs and a broad range of application
The maximum residue levels (MRL) for acetamiprid

An advertising copy of NN insecticides is “safe andare very high for fruits and tea-leaves in Japan.

mild”. In fact, deaths by acute neonicotinoid poisoning

Comparisons of MRLs of several NNs for some foodare rare in Japan because concentrations of NNs in

are shown in Table 4. The MRLs of imidacloprid and7)liquid formulations are low . However, acute oral

thiamethoxam are almost at the same level in theHuman neonicotinoids exposure in Japan

23

world; however the MRLs of acetamiprid, thiacloprid,

References

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Ⅴ. Conclusion
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Acknowledgements
I wish to thank to all of my co-workers, Yoshiko Aoyama at

Jpn J Clin Ecol 21: 24-34, 2012 (in Japanese)8 ) Japan Plant Protection Association: Handbook of Pesticide,
Japan Plant Protection Association. 2011, pp 65-75 (inAoyama Allergy Clinic, Kazutoshi Fujioka at Hawaii Instituteof Molecular Education, Motoyuki Kamata at Kanto-Gakuin
University, Toru Aoi at Gunma National College of Technology,

Japanese)9 ) Food Safety Commission of Japan, Ed. Noyaku Hyokasyo(Pesticide Evaluation Report) Acetamiprid. Food Safety

Tomonori Kawakami at Toyama Prefectural University,
Tomiko Yoshihara at Tokyo Kasei University, Naomichi
Moribayashi at Kiryu Kosei General Hospital, Mayumi
Ishizuka, Yoshinori Ikenaka, and Shyota Nakayama at
Hokkaido University, Kensaku Imai and Yoshifumi Ujiie at
Genaris, Inc. I thank to Professor Makiko Komori at Tokyo
Women’s Medical University for completing the ethicalprocedure to collect human urine samples.

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Funding

matter (PM 2.5) by microwave-assisted extraction andThis study is partially supported by Japan Endocrine-

liquid chromatography-tandem mass spectrometry. J

disruptor Preventive Action. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript. No additional external funding

Chromatogr A. 1216: 8817-8827, 200914) Yamamoto A, Terao T, et al. Evaluation of river pollutionof neonicotinoids in Osaka City (Japan) by LC/MS withreceived for this study.
Conflict of interest
The author has declared that no competing interest exists.

dopant-assisted photoionization. J Environ Monit. 14:
2189-2194, 201215)

Ichikawa Y, Moriyama M, et al. Drift monitoring ofacetamiprid sprayed by an air-blaster to pine trees inGunma Pref. Nihon Nohyaku Gakkaishi 33:281−288,
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日本人のネオニコチノイド曝露
要約
ネオコチノイド系殺虫剤は、日本では92年から使われ、09農薬年度の出荷量は407t だった。水溶性、浸透性、低揮発性、熱安定性で、作物、土壌、自然水中で持続的に効力を発揮し、摂取後、腸管粘膜、脳血液関門、胎盤を通過する。使用増加に伴い、環境中毒と思われる症例が見出されている。
04年、05年にアセタミプリドの地上散布後、各78、63人が受診し、頭痛、筋痛、胸痛、発熱、手指振戦、記憶障害、心電図異常がみられた。
06年以降、国産果物・野菜500g/日または茶飲料500mℓ/日以上を連日摂取し体調不良を訴えた患者が4,000人以上受診し、うち可逆性の短期記憶障害、手指振戦、心電図異常、頭痛、全身倦怠、発熱、咳、動悸、胸痛、腹痛、筋痛/筋攣縮を訴えた患者の尿中からネオニコチノイド代謝産物の6-クロロニコチン酸
7.5-84.8ng/mℓ、N-デスメチル-アセタミプリド3.2ng/mℓを検出した。
（臨床環境 23：14－24，2014）《キーワード》ネオニコチノイド、殺虫剤、アセタミプリド、イミダクロプリド、中毒