Toxicology, 1 (1973) 43--62

© Elsevier/North-Holland,Amsterdam - Printed in The Netherlands

S U M M A R Y O F R E C E N T S T U D I E S IN J A P A N
ON METHYL MERCURY POISONING *

KOHEI KOJIMAa and MASAHIKO FUJITA b

a Food Chemistry Division, Environmental Sanitation Bureau,
Ministry of Health and Welfare, Tokyo, and bDivision of Pharmaceutical
Science, National Institute of Public Health, Tokyo (Japan)
(Received July 21st, 1972)

CONTENTS

I. Further observations on methyl mercury in the environment 43

II. Further studies of the methylation of inorganic mercury and the
decomposition of organic mercury 45
III. Clinical and pathological studies on patients 47
IV. Animal studies on metabolism 51
V. Animal studies on pathology and toxicology 54
VI. Levels of mercury in the human body 57
References 58

I. FURTHER OBSERVATIONS ON METHYL MERCURY IN THE ENVIRONMENT

F a t e o f the m e r c u r y p o l l u t i o n in the M i n a m a t a district

I r u k a y a m a et al. 2 5 , 2 1 , 2 0 i n v e s t i g a t e d t h e p r e s e n t s t a t u s o f m e r c u r y
p o l l u t i o n in t h e M i n a m a t a d i s t r i c t w h e r e M i n a m a t a disease h a d first b e e n
d e s c r i b e d . No n e w case o f t h e d i s e a s e has b e e n r e p o r t e d since 1 9 6 1 , b u t it
was c o n s i d e r e d t h a t f u r t h e r s m a l l d i s c h a r g e s o f m e r c u r y c o m p o u n d s h a d
occurred from the Minamata Factory until June 1966, after which date the
s y s t e m o f w a s t e t r e a t m e n t was c h a n g e d c o m p l e t e l y . T h e p r o d u c t i o n of
a c e t a l d e h y d e in t h i s f a c t o r y was d i s c o n t i n u e d in M a y 1 9 6 8 .
T h e m e r c u r y level o f l o c a l fish a n d shellfish fell r e m a r k a b l y in 1 9 6 8 a n d
the ratio of methyl mercury to total mercury tended to be reduced. The
m e r c u r y c o n t e n t o f t h e hair of 201 i n h a b i t a n t s in M i n a m a t a c i t y was
d e t e r m i n e d . T h e levels s h o w e d a t e n d e n c y t o g r a d u a l d e c r e a s e in 1 9 6 8 .
H o w e v e r , h a i r m e r c u r y levels in f i s h e r m e n a n d t h e i r f a m i l i e s r e m a i n e d h i g h e r

* Those reports which were reviewed in "Methyl mercury in fish: A toxicological--epi-

demiological evaluation of risks, Report from an expert group, Stockholm 1971" and
in "Minamata disease, Study group of Minamata disease, Kumamoto University, Japan
1968" are not included in this summary.

43
than those found in the general population and were still above 20 ppm in
November 1968 in 4 out of 48.
Fujiki et al. 5 determined the amounts of m e t h y l m ercury in the "navel-
strings" o f the inhabitants in Minamata district, which had been kept in their
homes and r epor t e d that the levels of m e t h y l m ercury present showed
similar variation to those detected in the shellfish H o r m o m y a mutabiIis
(Gould) from Minamata bay. F r o m these results t h e y estimated that the
contamination with m e r c u r y began in about 1948, reached its peak a b o u t
1958, and gradually decreased thereafter.

Occurrence of m e t h y l mercury in the chlorine industry

Yamaguchi et al. 82 reported that m e t h y l m ercury was found in the
n e i g h b o u r h o o d of a caustic soda f a c t o r y where only metallic m e r c u r y had
been used industrially. Most of m e t h y l m ercury occurred in the sludge of a
t r e a t m e n t pit where spent calcium carbide was added to neutralize the water
from the electrolysis plant. It was shown experimentally that m e t h y l mer-
cury can be produced by the reaction of inorganic m e r c u r y with calcium
carbide.

Mercury in river sediment and fish

Aoki 2 investigated the inorganic and m e t h y l m ercury levels in the b o t t o m
sediment of rivers and in fish caught in these rivers. The average of three
different surveys in 1968--1969 was 0.77 ppm of total m ercury in the flesh
of fish caught in the Oyabe River where higher a m o u n t s of m ercury were
f o u n d in the b o t t o m muds. Catfish which live on the b o t t o m contained the
highest amounts, i.e. 1.10 ppm of total and 0.66 ppm of m et hyl mercury.
Fish in rivers which were flowing through areas of m e r c u r y mining contained
particularly high levels of mercury. The results revealed generally t hat the
higher the total m e r cur y level, the higher the level of m e t h y l m e r c u r y found.
Yamanaka et al. 83 determined the levels of m e r c u r y in tuna fish and in
the hair of crews of tuna-fishing boats. The level of m e r c u r y in tuna fish did
n o t depend on the fishing area, but on the species of tuna. The m e r c u r y
levels f o u nd in the hair were about four times as high as the average levels in
the Japanese population with respect to total m e r c u r y and 6 to 7 times as
high with respect to m e t hyl mercury.

A c c u m u l a t i o n o f m e t h y l mercury in fish
F u r th er studies on the accumulation of m e t h y l m ercury in fish and
shell-fish f r o m water containing m e t h y l m e r c u r y were report ed by Kita-
mura 3 6 T e r a m o t o et al. 71 and Kashimoto et al. 31. Fujita et al. 6 investi-
gated the role of plankton which represents the link between water and fish
in the f o o d chain in order to gain insight into the mechanism of accumula-
tion and transference of mercury. After addition of mercuric chloride t h e y
observed a rapid uptake of m e r c u r y from water by fresh water diatoms, the
max imu m being attained after the first 7 hours. Diatoms c o n c e n t r a t e d

44
mer cu r y to 1.4--6.1 • 104 times the concent rat i on found in fresh water on
the surface of their bodies.
Hashizume et al. 14 studied the accumulation and transportation of ethyl
mer cu r y in t h e f ood chain using a model stream. Benthic algae accumulated
80% to 90% of ethyl m er c ur y within one or t w o days after the addition of
ethyl mercury. E t hyl m e r c u r y was n o t d e c o m p o s e d in the water, but decom-
posed rapidly in algae and slowly in insect larvae.

Levels o f mercury in birds and animals

An investigation into the residual m e r c u r y in five Japanese storks which
had died during 1965- - 1966 was r e port ed by Muto and Suzuki 47. The
a m o u n t f o u n d in the birds, 4.6--13.4 mg/kg, was nearly as great as the lethal
dose and this was assumed to have derived from the small fish polluted with
m e r c u r y which had been consumed by these birds.
Takizawa et al. 69 f ound higher a m ount s of mercury, including m e t h y l
mercury, in the bones and remains of the organs of the cadaver of a cat
which had died in 1964 with neurological symptoms. The cat had lived in the
district near the up-stream area of the Agano River. T hey concluded from
these findings that the m e r c u r y pollution of the river had already occurred
prior to June 1964, the year of the Niigata earthquake.

II. FURTHER STUDIES OF THE METHYLATION OF INORGANIC MERCURY AND

THE DECOMPOSITION OF ORGANIC MERCURY

M e t h y l a t i o n o f mercury
Since Jensen and JernelSv f o u n d that inorganic m e r c u r y was converted
into meth yl m e r c u r y by some organisms, the mechanism of this m e t h y l a t i o n
has been the subject of further investigations in Japan. Kim et al. 34 found
that n o n - e nz ym at i c m e t h y l a t i o n t o o k place by the reaction of methylco-
baloximes with mercuric chloride in a phosphate buffer solution in the
absence of any reducing agent. The m e t h y l a t i o n proceeded at a remarkably
high rate following simple mixing of m et hyl cobal am i n with inorganic mer-
cury and produced di m e t hyl m e r c u r y as an initial p r o d u c t of the reaction
(Imura et al. 16).
Kitamura et al. 42,39 discovered a mercury-resistant bacterium and a
species of Neurospora sitophila, which were able to form m e t h y l and ethyl
m e r c u r y c o m p o u n d s when these micro-organisms were incubated in a culture
medium containing mercuric chloride.
Ukita and Imura 78 studied the possibility of m e t h y l a t i o n of inorganic
mer cu r y by various fish-liver homogenates. T h e y f o u n d that yellow fin
tuna-liver h o m o g e n a t e converted inorganic m e r c u r y to m e t h y l m e r c u r y after
allowing the mixture to stand in the dark for 5 h at 37 °. The same result was
observed using an h o m o g e n a t e sterilized at 120 ° for 15 min. T h e y did not
observe such m e t h y l a t i o n reactions with other fish and mammalian liver
homogenates.
The causative agent of Minamata disease around Minamata bay had been

45
 shown to be methyl mercury present in the waste water of a local acetalde-
hyde plant. Irukayama et al. 24 reported on the mechanism of the reaction
by which methyl mercury was formed in the plant. Tajima 61,62 studied the
mechanism of formation of methyl mercury from inorganic mercury by
reactions with acetaldehyde, acetylene, peracetic acid, etc. Yamaguchi et
al. 82 found methyl mercury to be present in the neighbourhood of a caustic
soda factory where only metallic mercury had been used in the manufac-
turing process. Most of the methyl mercury occurred in the sludge of a
treatment pit for effluent water that contained inorganic mercury. It was
shown experimentally that methyl mercury is produced by the reaction of
inorganic mercury with calcium carbide, the spent residue of which is added
to the pit in order to neutralize the effluent water. It was also reported that
traces of methyl mercury were produced in reactions of inorganic mercury
with amorphous carbon.
Tajima 63 who administered mercuric chloride orally to rats to study in
vivo the possibility of the transformation of inorganic mercury to m e t h y l
mercury found no evidence of transformation. Similar results were seen in a
group given mercuric chloride and ethyl alcohol, which is metabolised to
acetaldehyde in vivo. Kitamura et al. 41 administered orally mercuric chloride
solution to rats and determined m e t h y l mercury and total mercury in blood,
liver, kidney, brain and hair. Methyl mercury was found at higher levels in
the blood and kidneys than in the control group.
Kitagawa and Abe 35 analyzed commercial pesticides containing phenyl
mercuric acetate and found a maximum of 3% methyl mercury impurity.
They assumed that the methyl mercury compound was produced by decom-
position of phenylmercury acetate.
Akagi et al.1 reported that mercuric chloride was methylated by meth-
anol, ethanol or acetic acid in aqueous solution under the influence of UV
light of wave-length 360 mp, and that mercuric chloride was converted to
methyl mercury and ethyl mercury by propionic acid under the same
condition.
Kitamura and Sumino 38 studied the possibility of the methylation of
inorganic mercury by organic compounds in aqueous solution under the
influence of UV irradiation. In the presence of acetone or acetaldehyde 20%
to 30% of mercuric chloride was methylated. The conversion occurred
within 15 to 30 min of irradiation with UV light, the a m o u n t formed
reached a m a x i m u m after 1 to 2 h, and decreased gradually after this period.

T h e d e c o m p o s i t i o n o f organic mercurials by o t h e r chemicals

In order to eliminate and reclaim the mercury compounds in industrial
discharges, Irukayama et al. 18 treated the mother liquor containing methyl
mercury in an acetaldehyde plant with aluminium powder and aluminium
chloride. Nakamura 48 studied the decomposition of organic mercurials to
inorganic mercury compounds by chlorination, ozonization, and aluminium
powder and hydrochloric acid to find a satisfactory m e t h o d of treatment of
the waste water containing organic mercury compounds. Irukayama et al. 19

46
r ep o r ted that the m e r c u r y com pou nds, including m e t h y l m ercury com-
pounds in waste water f r om a vinylchloride plant could be removed by
t r e a t m e n t with aluminium powder, exchange resin and sodium sulphide.

The decomposition of organic mercurials by micro-organisms

T o n o m u r a et al. 76,75,74 isolated a mercury-resistant pseudomonas from
soil which was heavily c o n t a m i n a t e d with phenylmercuric acetate. The
organism was capable of decomposing phenylmercuric acetate, ethylmercuric
phosphate and m e t h y l m e r c u r i c chloride to metallic mercury. Benzene,
ethane and m et hane were also identified as decomposition products of
phenylmercuric acetate, ethylmercuric phosphate and m et hyl m ercuri c chlo-
ride, respectively. Fur uka w a et al. 9, T o n o m u r a and Kanzaki 73 and Fur-
ukawa and T o n o m u r a 10 r e por t ed that the cleavage of the C--Hg bond in
phenylmercuric acetate and ethylmercuric phosphate was catalyzed by a
cell-free e xt r a c t of the pseudomonas in the presence of a sulfhydryl com-
pound, and t hat this reaction was coupled with NADH or NADPH f o r m a t i o n
by glucose-dehydrogenase.
The mercury-resistant bacterium Pseudomonas K62 strain was used by
Suzuki et al. 55 in a t t e m p t s to remove mercurials in industrial waste. The
organisms were incubated in a mercurial solution to allow take-up of mer-
cury, the cells were t he n transferred t o culture medium and incubated with
shaking for 6 h. During this period a b o u t 70% of cell-bound m ercury was
vaporized.

Decomposition o f organic mercurials by plants

Takeda et al. 66 showed experimentally that organic mercurials are de-
composed not only in the roots but also in other organs of the soybean. The
d eco mp o s i t i on rates were f o u n d to decrease in the following order: ethyl-
mercuric chloride > but yl m er c ur i c chloride > phenylmercuric chloride >
m e t h y l m e r c u r i c chloride 65. Cysteine and d i h y d r o t h i o c t i c acid were found
to accelerate the decom pos i t i on of m e t h y l m e r c u r y c o m p o u n d s in vitro. This
fact appears to be one of the reasons for the rapid decomposition of
phenylmercuric acetate in plant tissue 28

III. CLINICAL AND PATHOLOGICAL STUDIES ON PATIENTS

F u r th er clinical and pathological studies have been carried out on patients

in the Minamata and Niigata districts.

(a) Follow-up o f Minamata cases

T o k u o m i 72 investigated the s y m p t o m s in 26 Minamata patients who had
had characteristic s y m p t o m s of Minamata disease more than 10 years ago,
and observed some i m p r o v e m e n t in the symptoms.
Partial recovery f r om visual field constriction was clearly observed in a
few cases. Impairment of hearing had improved compared with findings 10
years ago, in 60% of the patients particularly in the high pitch t o n e area. The

47
hearing became better generally, except in cases of deafness. Ataxic walking
and writing also recovered partially but not fully. T r e m o r of fingers was
f o u n d in 54% of the patients instead of 75% of patients 10 years ago.
Disturbances of superficial sensation were observed in 80% of the patients,
but the e x t e n t of the disability had decreased considerably. Disturbance of
deep sensation was present in 58% instead of 100% of patients and was less
severe. On the other hand, salivation and sweating persisted in some cases,
and almost all patients still had physical difficulties and were unable to live
ordinary lives. No other clinical characteristic findings were observed apart
from the neurological ones.
Takeuchi e t al. 67 noticed that some of the s y m p t o m s of central and
peripheral nervous system disturbance persisted unchanged, whilst some
symptoms, such as mental and character abnormalities had b e c o m e worse
during the past 10 years in the Minamata patients.
The most remarkable pathological change was observed in the white
matter o f the brain. The degenerative changes which were n o t clear after
2--3 years, had now b e c o m e rather more obvious after 4--6 years, and had
also b e c o m e m or e widespread after 10 years. In m any cases gross changes
were f o u n d including sclerosis in some. Thinning of the myelin sheaths was
noticeable. The ot her remarkable change was degenerative thinning of the
cerebral cortex.
Hyperplasia of neuroglia, and repair Of injured peripheral nerves, i.e.
cicatrization and increase of collagen, were also observed. Evidence of
degeneration of peripheral nerve fibres might be an i m p o r t a n t finding in
order to judge the progress of the disease. Unusual thickness of the axis
cylinders and n e u r o l e m m a were often observed.
R ed u cti on of the weight of the brain was generally noted, but there was
no significant difference between acute, subacute and chronic cases. The
mer cu r y c o n t e n t of organs including brain reduced rapidly during the first 3
months, but m or e gradually during the subsequent 1--2 years, and some
amounts, rather higher than the normal levels were still found even after 10
years.
Harada e t al. 13 investigated the status of affected babies suffering from
Minamata disease including congenital cases. Of the 121 cases found in the
Minamata district during 1953--1960, 23 were congenital cases (3 died later)
and 30 others were infants (10 of those died later). T h e y were now aged
10--15 years and 15--19 years, respectively. Ataxia and speech disturbances
had persisted in almost all congenital cases, disturbance of chewing and
swallowing had recovered fairly well but were still present in about half of
the cases. Involuntary m o v e m e n t and pathological reflex changes had de-
creased. Abnormal electroencephalograms were observed in two-thirds of the
cases. Recovery of the s y m p t o m s was better in affected infants than in
congenital cases; ataxia and disturbance of speech had improved in one half
of the cases, and impairment of hearing, disturbance of chewing and swal-
lowing was present in less than one-third of cases. Constriction of visual field

48
was still observed in e v e r y case in which the test c o u l d be carried on. T h e
m e r c u r y level in t h e hair had r e t u r n e d to a b o u t normal.
As m e n t i o n e d above, the m o r e severe cases were f o u n d a m o n g t h e con-
genitally ai~ected patients and less severe cases in the i n f a n t patients. This
implies t h a t s y m p t o m s were severe and disorders were m o r e extensive in
y o u n g e r patients, and t h a t r e c o v e r y was less likely.
A l t h o u g h the m o t h e r s o f the c o n g e n i t a l l y a f f e c t e d patients s e e m e d to
have ingested r a t h e r large a m o u n t s o f m e r c u r y during their pregnancies, no
t y p i c a l s y m p t o m was observed a m o n g t h e m , and o n l y in few cases were
slight n u m b n e s s of limbs and neuralgic-like s y m p t o m s observed. This also
c o n f i r m e d the age d i f f e r e n c e in the sensitivity to organic m e r c u r y poisoning.
S o m e of these y o u n g patients w i t h slight s y m p t o m s had since married and
had given birth to h e a l t h y children, and t h e s u b s e q u e n t children o f t h o s e
m o t h e r s w h o previously had had a congenitally a f f e c t e d child were n o w also
healthy.
T h e o n s e t of m e n s t r u a t i o n was n o t d e l a y e d in t h e congenitally a f f e c t e d
f e m a l e patients e x c e p t in very severe cases. This was i n t e r p r e t e d as showing
t h a t organic m e r c u r y does n o t seriously i n t e r f e r e with r e p r o d u c t i v e capacity.
The c h r o m o s o m e s of these patients were e x a m i n e d b u t no special abnormali-
ties were f o u n d .
E t o h 4 r e p o r t e d characteristic findings in t h e peripheral nerves o f 3
c h r o n i c patients w h o had d e v e l o p e d s y m p t o m s a b o u t 10 years ago. B i o p s y
specimens o f the s e n s o r y p o r t i o n o f the sural nerve s h o w e d on light
m i c r o s c o p y disappearance o f nerve fibres with collagen proliferation, irregu-
lar size and irregular a r r a n g e m e n t s of nerve fibres, and irregular p r o l i f e r a t i o n
o f S c h w a n n ' s cells in all cases. E x a m i n e d b y e l e c t r o n m i c r o s c o p y , t h e sural
nerve s h o w e d scars with increasing collagen and variable changes in the nerve
fibres, particularly irregular and i n c o m p l e t e r e g e n e r a t i o n . E x t r e m e l y small
a x o n s o f irregular size as well as lamellar processes o f the c y t o p l a s m o f
S c h w a n n ' s cells were p r e s e n t in increased n u m b e r s .
T h e entire p i c t u r e of M i n a m a t a disease appears t o have clarified. H o w e v e r ,
Harada 12 stated t h a t all aspects o f t h e disease had n o t y e t been clarified.
T h e m e r c u r y p o l l u t i o n had been f o u n d in o t h e r districts, and m a n y cats were
observed t o have s y m p t o m s in districts w h e r e no h u m a n poisoning case had
b e e n f o u n d . Higher levels o f m e r c u r y in the hair of p e o p l e were observed
w i d e l y in places very distant f r o m M i n a m a t a and no investigations had been
d o n e to show their s u b s e q u e n t fate. T h e onset of poisoning had been
t h o u g h t to have o c c u r r e d in 1 9 5 3 - - 1 9 6 0 , b u t some evidence for its presence
as early as 1 9 4 6 had been discovered.
T h e s y m p t o m s of the disease had changed and it s e e m e d a p p r o p r i a t e at
present t o add a new variant of the disease in w h i c h the main s y m p t o m s
were t h o s e o f m e n t a l and c h a r a c t e r disorder. T h e r e were also such facts as
the o b s e r v a t i o n o f a higher rate o f f e e b l e - m i n d e d n e s s in the district w h e r e
poisoning had o c c u r r e d during the period resulting in c o n g e n i t a l l y a f f e c t e d
babies.
F u t a t s u k a e t al. 11 investigated the physical state o f m i d d l e s c h o o l pupils

49
b o r n during the period w h e n m a n y cases of Minamata disease occurred. T h e y
s h o w e d no i n t e r f e r e n c e w i t h regard to height and weight or physical state
b u t t h e r e a p p e a r e d to be widespread slight loss o f c o o r d i n a t i o n o f m o v e m e n t
and slight peripheral sensory loss.

F o l l o w up o f Niigata cases
Shirakawa et al. 53 studied the e l e c t r o e n c e p h a l o g r a m s ( E E G ) o f patients
in the Niigata district. 23 out o f 26 patients and 9 persons w h o had had no
neurological s y m p t o m s b u t had been s h o w n to have m o r e t h a n 200 p p m o f
m e r c u r y in their hair were selected. 3 persons w h o had o t h e r illnesses were
e x c l u d e d and the remaining 28 persons were tested. T h e results were classi-
fied into ( 1 ) m o n o r h y t h m i c f r o n t a l t h e t a p a t t e r n ; ( 2 ) i r r e g u l a r slow wave
p a t t e r n ; ( 3 ) l o w voltage E E G p a t t e r n including (a) low voltage with slow
waves, (b) low voltage with fast waves and (c) low voltage with alpha waves;
(4) diffuse alpha pattern; and (5) n o r m a l p a t t e r n .
The results of the test at the onset o f s y m p t o m s were c o m p a r e d with t h o s e
a f t e r one year.
Pattern at onset after one year

(1) 2
(2) 3 5
(3) a 4
b 4 5
c 4 4
(4) 6 1
(5) 5 7
Total 28 22
As had b e e n observed in o t h e r studies o n m e r c u r y poisoning, low voltage
E E G p a t t e r n s and diffuse alpha p a t t e r n s were m o r e f r e q u e n t l y f o u n d at the
onset o f s y m p t o m s . No positive c o r r e l a t i o n b e t w e e n s y m p t o m s and E E G
p a t t e r n s was observed, e x c e p t t h a t m o n o r h y t h m i c f r o n t a l t h e t a p a t t e r n
o c c u r r e d in the serious cases.
T h e u n i p o l a r lead EEGs f r o m the occipital position were c o m p a r e d at
onset of s y m p t o m s with t h o s e after one year. No statistically significant
differences were n o t e d b u t it s e e m e d t h a t the a m p l i t u d e s had b e c o m e a little
larger. T h r e s h o l d values were tested b y the p e n t a z o l activation m e t h o d a f t e r
o n e year f r o m the onset of the s y m p t o m s . T h e value was lower t h a n any
c o n t r o l and the irregular slow wave p a t t e r n was observed m o r e f r e q u e n t l y at
lower t h r e s h o l d values. No positive c o r r e l a t i o n was observed b e t w e e n E E G
p a t t e r n s and the m e r c u r y c o n t e n t of b l o o d and urine. It was assumed that
the E E G changes were related to i n t e r f e r e n c e with the cortical f u n c t i o n and
general cortical p r o j e c t i o n system.

50
IV. ANIMAL STUDIES ON METABOLISM

Kats u n u m a et al. 33 investigated the distribution of m e r c u r y in the blood of

rabbits given mercuric nitrate, phenyl m ercuri c acetate, m e t h y l m e r c u r i c
chloride, ethylmercuric chloride of merthiolate. The m e r c u r y was divided
almost equally between the red corpuscles and the plasma after administra-
tion of mercuric nitrate. The decrease in the c o n c e n t r a t i o n of m ercury in the
plasma was larger than in the red corpuscles after a single administration of
mercuric nitrate. Almost all of the m e r c u r y was found in the red blood
corpuscles after administration of alkyl mercuric chloride and merthiolate;
only one-sixth of the m e r cur y of phenylmercuric acetate remained in the
plasma, five-sixths were f o u n d in the corpuscles. The m ercury in the red
corpuscles was f ound to be present b o t h in the stroma and the endoplasma
after administration of mercuric nitrate and phenylmercuric acetate, but
after ethylmercuric chloride it was f o u n d mainly in the stroma.
I r u k a y a m a et al. 17 c om par e d the metabolism of m e t h y l m e r c u r i c sulphate
and m e t h y l m e r c u r i c iodide. Cats fed {CH3Hg)2SO 4 developed the same signs
and s y m p t o m s as cats fed the poisonous seafood from Minamata bay. The
o r g a n o m e r c u r y c o m p o u n d present in organs such as the liver, the kidney,
and the bone marrow of the treated animals did not extract with chloro-
form, but it was easily removed by BAL. The m e t h y l m e r c u r y c o m p o u n d in
the organs of cats fed (CH3Hg)2SO 4 and rats fed CH3HgI was found to be
the same c o m p o u n d . The excretion of m e r c u r y in the faeces of cats fed
(CH3Hg)2SO 4 was considerably smaller com pared with that of cats fed
CH3HgC1 and (CH3Hg)2S.
Kameda 30 determined the level of m e r c u r y in the peripheral nerves of
rats poisoned with m e t h y l mercury. The ratio of the m e r c u r y c o n c e n t r a t i o n
in peripheral nerves to that of the brain was 1:2. A m e r c u r y level exceeding
at least 10 ppm was required to cause the neurological s y m p t o m s accom-
panied by morphological changes in the peripheral nerves. Mercury increased
rapidly in the peripheral nerves following administration of m e t h y l m e r c u r y
but decreased more gradually after discontinuance of administration. How-
ever, a small a m o u n t of m e r c u r y (3.1 ppm) could still be det ect ed at the end
of the experiment, i.e. 102 days after discontinuance of the administration
of m e t h y l mercury. It was concluded from these experiments that m e t h y l
m e r c u r y passed the blood-nerve barrier.
Katsuno and K o n d o 32 f o u n d that there was a linear logarithmic relation-
ship between the dose administered and the level of m e t h y l m e r c u r y in the
red blood corpuscles of the rat over an oral dose range of 0.16 to 16
p g / d a y / r a t . The level of m e t h y l m e r c u r y in red blood corpuscles 70 days
after a single administration of 1.12 mg of m e t h y l m e r c u r y to rats was
almost the same as that following daily administration of 0.112 mg of
m e t h y l m e r c u r y for a total of 70 days.
Hirota 15 studied the distribution of m e t h y l m e r c u r y in various organs of
the rat following a single intramuscular administration of 10 mg/animal or 1
mg/animal. The results are set out in Table I. Methyl m ercury c o n t e n t was

51
TABLE I
MEAN METHYL MERCURY CONTENT OF ORGANS OF 37 ADULT RATS AFTER
SINGLE ADMINISTRATION OF 10 mg METHYLMERCURIC CHLORIDE (MMC)

Time after Number Concentration of methyl mercury (pg MMC/g wet tissue)
administration of rats Mean values + S.D.
(days)
Brain Liver Kidney Blood

1 6 2.58 +0.8 42.2+18.4 59.1+ 4.7 198.0+88.7

5 7 13.7 +6.8 60.2_+ 9.4 89.4_+28.0 210.7_+69.5
10 6 14.7 +4.2 46.5+16.5 79.6_+14.5 201.5 +_73.4
15 6 22.8 +8.9 44.7_+16.8 73.0+ 8.5 198.4_+54.1
20 6 15.3 -+7.6 34.0+14.0 44.0+13.5 177.9+60.4
25 2 10.6 -+2.6 24.0+ 2.0 38.2_+10.6 82.0_+25.7
30 2 7.75+0.2 21.9+ 1.8 32.9+ 2.0 7 6 . 7 _ + 6.0
40 2 4.95+0.5 11.5+_ 5.4 19.0+ 2.5 42.5_+12.7

highest in the b l o o d and lower in the k i d n e y , liver and brain. The levels in
blood, liver and k i d n e y decreased linearly w h e n p l o t t e d on a semilogarithmic
curve over a period o f 40 days. A c c u m u l a t i o n of m e t h y l m e r c u r y in and
elimination f r o m the brain a p p e a r e d to be slower t h a n in the liver and
kidney.
The levels o f m e t h y l m e r c u r y in the brain o f rats were highest in the
cerebellum, c e r e b r u m and brain stem in t h a t order. No significant d i f f e r e n c e
was n o t e d b e t w e e n the f r o n t a l and occipital parts of the c e r e b r u m . M e t h y l
m e r c u r y c o n t e n t in the brain was slightly higher in t h o s e rats with n e r v o u s
m a n i f e s t a t i o n s t h a n in t h o s e w i t h o u t t h e m . In patients w h o had died o f
M i n a m a t a disease, n o d i f f e r e n c e was observed in the a m o u n t s of m e t h y l
m e r c u r y d e p o s i t e d in the various parts o f the brain e x c e p t for t h e pons and
cervical cord w h e r e the levels were lower t h a n elsewhere.
Suzuki e t al. 58 a d m i n i s t e r e d s u b c u t a n e o u s l y or i n t r a v e n o u s l y m e t h y l ,
p h e n y l or inorganic m e r c u r y c o m p o u n d s to rabbits, rats and mice. T h e y
assayed the m e r c u r y c o n t e n t in various areas o f dissected brains and with
m e t h y l m e r c u r i c acetate, f o u n d the highest c o n t e n t to be in the cerebral
cortex, the n e x t highest in the cerebellum and the lowest in the brain stem.
With p h e n y l m e r c u r i c acetate or inorganic m e r c u r y , the highest c o n c e n t r a t i o n
was f o u n d in the cerebellum and the lowest in the cerebral c o r t e x . The
biological half-life o f m e t h y l m e r c u r i c acetate in the w h o l e brain or each
c o m p a r t m e n t was a b o u t 6 or 7 days, b u t t h a t o f p h e n y l m e r c u r i c a c e t a t e was
a b o u t 2 weeks at the lower dose level and a b o u t 20 days at the higher level.
K i t a m u r a e t al. 4 ° investigated the a c c u m u l a t i o n o f m e t h y l m e r c u r i c
chloride fed to mice. The g r o u p given the lowest daily dose o f 0.1 p p m in
diet did n o t show a n y a c c u m u l a t i o n , b u t the groups receiving 0.2 p p m and
0.5 p p m Slightly a c c u m u l a t e d m e t h y l m e r c u r y in the w h o l e b o d y , the
digestive organs and the fur. T h e a c c u m u l a t i o n o f m e t h y l and t o t a l m e r c u r y

52
observed in the group given 1.0 ppm was remarkably high. T h e y concluded
that m e t h y l m e r c u r y was absorbed and rapidly d e c o m p o s e d in the body.
Using low levels of administration, Taguchi 60 studied the absorption,
excretion, and accumulation of m e t h y l m e r c u r y in vivo in mice, and its
transplacental passage into the foetus in the rat. He found the following rates
of absorption of m e r c u r y c o m p o u n d 6 h after oral administration from the
digestive tract: m e t h y l m e r c u r i c chloride 73%, phenylmercuric acetate 45%
and mercuric acetate 6%. Mercury levels in the bodies of mice given solid
foods containing m e t h y l m e r c u r i c chloride (equivalent to 1.0 ppm m ercury)
showed an apparent increase. But further experiments revealed that there
was a limit to the accumulation of m e t h y l m e r c u r y after about 75 days, the
value being a b o u t 40 pg.
23.2% of the total dose of m e t h y l m e r c u r i c chloride administered to the
m o t h e r passed into the foetus. Methylmercuric chloride concentrations in
the brain and liver were higher in the foetus than in the mothers. The
mer cu r y levels in blood and hair apparently showed lower values in pregnant
rats than in the non-pregnant rat. Compared with the findings in human
mothers and their new-borns, the m e r c u r y c o n t e n t in the blood corpuscles
was higher and t h a t of serum was lower in new-born rats.
Takahashi e t al. 64 and Ukita e t al. 8 ° studied the t i m e - d e p e n d e n t
distribution of 203Hg-mercury c o m p o u n d s in rats and m o n k e y s by whole
b o d y autoradiography. The autoradiograms of rats injected with [203Hg]-
ethylmercuric chloride indicated an accumulation of radioactivity in almost
all organs which persisted longer than in the mouse. No difference was
observed between the two animal species after the administration of
[ 203 Hg] mercuric chloride.
Whole-body autoradiograms were prepared from rats and m o n k e y s at
different time intervals after b o t h intravenous and intraperitoneal adminis-
trations of [ 2 0 3 H g ] m e r c u r i c chloride or [ 2 ° 3 H g ] e t h y l m e r c u r i c chloride.
The distribution pattern in the whole b o d y differed greatly for the two
co mp o u n d s . The m o d e of migration and the accumulation of the radioac-
tivity in the central nervous system was observed more precisely in the
m o n k e y s than in the rats following administration of [ 203 Hg] ethylmercuric
chloride.
A p r o n o u n c e d accumulation of radioactivity was observed in the cortices
of the cerebrum and cerebellum, especially the occipital lobes of a m o n k e y 8
days after the administration of [203Hg] ethylmercuric chloride. The mer-
cury c o m p o u n d that had accumulated in the brain was extracted as dithi-
zonate and identified as ethylmercuric dithizonate. The t i m e-dependent
migration of m e r c u r y into the brain was m uch greater in the m o n k e y than in
the rat.
Autoradiograms of the central nervous system of the m o n k e y suggested
that ethyl m e r c u r y residue possibly passed into the central nervous system
through the blood-brain barrier, since the radioactivity first appeared in the
choroid plexuses, the intracranial and extracerebral arteries, and subsequently
became distributed t h r o u g h o u t the cerebral and cerebellar cortices after a

53
 time interval. There was no significant radioactivity in the areas adjacent to
the lateral ventricles in all of the autoradiograms prepared from the m o n k e y s
60 min, 20 h and 8 days after the administration of [ 2 ° 3 H g ] e t h y l m e r c u r i c
chloride.
Ukita e t al. 79 studied by whole-body autoradiography the distribution of
[2°3Hg]mercury c o m p o u n d s injected into normal and pregnant mice.
Ethylmercuric chloride and butylmercuric chloride accumulated in the liver,
kidney, lung and muscles. The ease of passage through the placenta was
observed to be as follows: ethylmercuric chloride > butylmercuric chloride
phenylmercuric chloride > mercuric chloride. The m e r c u r y c o m p o u n d s
passing the placenta were taken up by the central nervous system of the
foetus.
Suzuki e t al. 57 investigated the ret ent i on of m ercury by the t h y r o i d in
rats and rabbits. Considerable r e t e n t i o n was f o u n d with mercuric acetate,
phenylmercuric acetate and m e t h y t m e r c u r i c acetate. The height of follicle
cells in the t h y r o i d of rats increased and the changes became greater during
14 days after the injection of all three compounds.
The residues of m er c ur y in the b o d y were f o u n d to decrease as a result of
excretion as r e p o r t e d by Kitamura e t al. 37,38 and Kitamura 36. A point
exists at which the initial b o d y level reduces to half. T h e y named the period
to reach this point the biological half-life. T h e y proposed the hypothesis that
the more the b o d y burden increased, the greater the a m o u n t of excretion.
Using the equation d y / d t = k . y , or y = yo e - k t (in which y = the a m o u n t
present in the body; t = time; k = coefficient) t hey calculated the theoretical
biological half-life and the rate of accumulation of m e r c u r y compounds.
Sadakane 52 administered ethylmercuric phosphate to rabbits and rats
and studied its accumulation and distribution in these animals.

V. ANIMAL STUDIES ON PATHOLOGY AND TOXICOLOGY

Takizawa 68 fed fish from the Agano river to a cat and rabbits, and found
the same s y m p t o m s and histopathological changes as were seen in animals
given methyl m er c ur i c chloride. The m et hyl m e r c u r y contents of the organs
of each dead animal were investigated.
Nose 49 studied the t o x i c i t y of the lower alkylmercuric c o m p o u n d s in the
rat. He stated that the chemical structure bore a close relationship to the
manifestation of s y m p t o m s of poisoning and that the increase in the n u m b e r
of carbon atoms correlated with a diminution in the s y m p t o m s observed.
According to this investigator the higher alkyl m ercury com pounds, such as
n-butyl m e r cur y seemed to have little pathogenicity. He showed that the
greater p r o p o r t i o n of methyl-, ethyl-, n-propyl- and n-butylmercuric com-
pounds which were absorbed and which accumulated in various organs, were
metabolised by breakage of the C--Hg bond and were excreted as inorganic
mercury.
A hypothesis regarding the critical concent rat i on of m e r c u r y in the brain
necessary to induce neurological symptoms, was tested by Suzuki and

54
Miyama 56 by feeding methylmercuric chloride to mice. The most sensitive
and earliest sign i.e. the lessening of the capability to maintain the head in a
horizontal position when hung up by the tail, was noticed at brain concen-
trations of 10 ~g Hg/g. The group receiving 10 pg Hg/g in their diet as the
lowest level tested, did not show any loss of body weight or neurological
symptoms until the 41st day of feeding of mercury.
Ishikura e t al. 26 studied the toxicity of methoxyethylmercuric chloride.
Diets containing m e t h o x y e t h y l m e r c u r i c chloride or butylmercuric chloride
were fed to dd strain male mice. Significant differences were observed
between the growth curves of mice given methoxyethylmercuric chloride in
doses of 1250 and 2500 t~g Hg/day and that of the control. Specific neuro-
logical s y m p t o m s were observed in almost all animals of these two test
groups. In the case of m e t h o x y e t h y l m e r c u r i c chloride, the highest mercury
content was found to be in the liver, decreasing in the kidney, spleen and
brain, in that order. Mercury levels in the liver were higher in the group
receiving the highest dose, but no specific difference between the levels of
mercury detected was seen in the kidneys of all groups. Accumulation of
mercury in the brain was higher with butylmercuric chloride than with
methoxyethylmercuric chloride.
In order to study further the cause of congenital Minamata disease,
Tatetsu e t al. 7o administered CH3Hg S CH 3 orally to rats and found
degenerative changes in the brains of new-born pups from those mother rats
which had been given 5 mg/kg of the c o m p o u n d during 2--3 weeks of
pregnancy.
Miyagawa e t al. 46 administered orally daily 1 mg/animal of dimethylmer-
curic sulphide to rats for 12--20 days and investigated the pathological
changes in the granular cells of the cerebellum electron microscopically.
Remarkable changes were observed in the granular cells compared with other
sites. The selectivity of the changes appeared to be characteristic of m e t h y l
mercury and it was assumed that a disturbance of protein synthesis might be
involved. Mitochondria remained visible for long periods after the disap-
pearance of smaller organelles in the granular cells. Two types of degenera-
tive changes were observed in granular cells; in one the contents of the cell
nucleus emptied into the cytoplasm and in the other the nucleus appeared to
coagulate.
Fukuhara 7 studied by electron microscopy the changes in the cerebellar
granular cell layers after experimental m e t h y l mercury poisoning in rats. In
the granular cells some axonal swelling was observed at first, about half the
animals showing predominantly degenerating granular cells. The nuclear
contents appeared to be condensed into spots and the nuclear membranes
became dilated. The endoplasmic reticulum showed severe disintegration and
the cristae of the mitochondria were disrupted. In degenerating mitochon-
dria, abnormally dense granules (diameter 500--1000 A) were noticed and
the mitochondria condensed gradually into dense masses accompanied by
nuclear and cytoplasmic degeneration. Many degenerating granular cells
appeared to be invested with myelin lamellae, which were denoted "perika-

55
 ryal myelin". This had the same absorbance as the axonal myelin. The
f r eq u en cy of the occurrence of the perikaryal myelin correlated with the
degree of granular cell degeneration. The occurrence of the perikaryal myelin
was th o u ght to reflect n o t only excessive product i on of myelin, but also
some participation of .these abnormal granular cells in the clinical picture.
Axonal swellings were observed in the granular cell layers which were
packed with mitochondria, m e m br a nous dense bodies and vesicular ele-
ments. In pericytes on capillaries, m uch lipofuscin and lysosomes accumu-
lated, but the endoplasmic reticulum was well developed.
Matsumoto and Kameda 44 studied by electron microscopy the degenera-
tive changes in and regeneration of nerve fibres in mice with polyneuritis
induced by m e t h y l m e r cur y poisoning. At first coarsening of the axonal
myelin was observed and, in m a ny cases, the axis cylinder seemed to be more
dense. And in the next stage, the axonal myelin disintegrated and scattered
in the cytoplasm of the Schwann cells. Small organelles in the Schwann cells
disappeared completely and the cell membranes form ed complicated projec-
tions. The cell membranes of the non-medullated nerve fibres also f o r m e d
complicated projections. A b o u t one m o n t h after stopping administration of
the meth y l m e r c u r y following the appearance of neurological symptoms,
regeneration of nerve fibres was observed; m any axons were f o r m e d sur-
rounding the nucleus of the Schwann cell and small organelles in the
Schwann cell became active again. Eventually some axonal myelin form ed
around these new axons.
F u k u h ara e t al. 8 studies the pathological alterations in the blood-brain
barrier in rats poisoned with m e t hylm ercuri c chloride, by electron micro-
scopy. The contrast medium t h o r o t r a s t (24--26% colloidal t hori um dioxide)
was used to check the e x t e n t and ease of passage through the blood-brain
barrier. The rats were observed seven days after the intramuscular injection
of 10 mg m e t hyl m er c ur i c chloride. 0.5 ml of t h o r o t r a s t was injected into
rats of b ot h control and treated groups and animals were sacrificed 30 min
after injection.
The th or ot r a s t appeared as electron-dense irregular particles a b o u t
30--100 X in size. In the control group the t h o r o t r a s t particles were never
seen in the endothelial cells nor in basement m em brane of cerebral vessels.
On the other hand, in the treated group there appeared at first an increased
number of p i n o c y t o t i c vesicles within the endothelial cells of the brain
capillaries, and secondly, the interendothelial junctions were separated by
th o r o tr as t particles. Similar separation of cell junctions by t h o r o t r a s t were
seen in the basement membrane.
A few t hor ot r as t particles were also visible within the endothelial cells.
The t h o r o t r a s t particles which passed through the basement m em brane were
observed at first to be in the intercellular space but later t hey were detected
in the cytoplasm of the astrocytes around the capillaries.
Brown and Yoshida 3 studied the changes in the cerebellum of chicken
treated with dimethyl m er c ur y and m e t h y l m e r c u r i c nitrate by electron and
light microscopy.

56
 The earliest changes f ound were dilatation of the lamellae of the endoplas-
mic reticulum or Golgi complexes in b o t h Purkinje cell and granular cells.
The Golgi complex disappeared slowly from the neurons. RNA particles
became separated f r om membranes and, at the same time, enlargement of
nuclear pores was n o t e d with extrusion of nuclear material into the out er
membrane. Variable changes were f oun d in the pre- and post-synapse endings
of the cerebellar island. Some endings appeared relatively intact; others were
extensively vacuolated, had altered membranes and electron-dense inclu-
sions. The post-synapse endings of t e n had no organised structure. Many
electron-dense bodies were not e d in the endothelial and perithelial cells. The
Bergman glia adjacent to the capillary were markedly enlarged, of low
electron density and showed extensive alterations in the structure of their
mitochondria. Organic mercurial intoxication alters cell m em brane structures
and appears to interfere with protein p r o d u c t i o n in cerebellar neurons and
glia.
Ishikura and Yonaha 27 studied the effect of phenylmercuric acetate and
ethylmercuric phosphate on e r y t h r o c y t e cholinesterase of rat, human or
bovine. Both c o m p o u n d s inhibited this e n z y m e and the inhibition was
reversed by the addition o f cysteine. It was shown that phenylmercuric
acetate inhibited bovine e r y t h r o c y t e cholinesterase competitively and the
ethylmercuric acetate inhibited it non-competitively.
Matsumoto and Yamaguchi 45 studied the effect of various chemicals on
the ease of passage of mercurials through the lining of small intestine of the
rat. Cysteine accelerated the process, but L-methionine, thioacetamide,
glutamic acid, ethanol, EDTA and 2,4-dinitrophenol had practically no
effect on the permeability of the intestinal mucosa.
After reporting on the toxicities of mercuric com pounds, including
meth y lmer c ur i c chloride, on the chick e m b r y o following injection into the
egg and after administration to the hen, Kuwahara 43, Irukayam a and
Kuwahara 22 studied the effect of mercurials administered to the cock on
the hatchability of eggs. T h e y f o u n d no significant effect from methylmer-
curic chlorides administered at 600 pg (as Hg) per day over several months.
I r u k ay am a and Kuwahara 23 also r eport ed that the greater part of m e t h y l
mer cu r y administered to the hen transferred into the egg and accumulated in
the egg-white in com bi na t i on with albumin.
Iwata and O k a m o t o 29 administered either zinc, cadmium, manganese or
selenium with m e t h y l m e r c u r i c iodide, and studied the effects of these metals
on the to x i ci t y of m e t hyl mercury. Only selenium had an observable effect.
It reduced the toxic effect of m e t hyl m e r c u r y similar to the k n o w n effect of
selenium on inorganic m e r c u r y intoxication.

VI. LEVELS OF MERCURY IN THE HUMAN BODY

Yamaguchi 81 r e p o r t e d that the average concent rat i on of m e r c u r y in the

urine of 166 school children of 4 elementary schools was 4.8 + 0.43 pg/1.39
university students had an average c o n c e n t r a t i o n of 2.1 + 0.37 pg/1 equiv-

57
alent to an o u t p u t o f 2.0 ± 0.43 p g / d a y . T h e c o n c e n t r a t i o n o f m e r c u r y in
t h e b l o o d o f 18 u n i v e r s i t y s t u d e n t s was 5.3 ± 0.63 pg/1.
O h t a e t al. 51 d e t e r m i n e d t h e average c o n t e n t o f m e r c u r y in h u m a n
tissues o b t a i n e d f r o m 10 a u t o p s i e d adults w h o had n o t b e e n involved in
o c c u p a t i o n a l m e r c u r y e x p o s u r e . T h e m e a n m e r c u r y c o n t e n t in various fresh
h u m a n tissues was f o u n d to be as follows:
Hg ( p p m ) Hg ( p p m )
Brain 0.45 ± 0.33 Pancreas 0.45 + 0.52
Liver 0.49 + 0.31 Stomach (mucus) 0.45 ± 0.36
Heart 0.65 ± 0.59 Intestine (mucus) 0.38 ± 0.45
Kidney 0.86 ± 0.72 S u p r a r e n a l gland 0.61 ± 0.45
Lung 0.75 ± 0.73 T h y r o i d gland 0.59 ± 0.60
Spleen 0.47 -+ 0.41 Muscle 0 . 4 6 -+ 0.35
F r o m t h e s e data, it was e s t i m a t e d t h a t a b o u t 24 m g o f m e r c u r y was p r e s e n t
in a J a p a n e s e a d u l t o f a p p r o x . 50 kg b o d y weight.
O h t a a n d Terai 50 d e t e r m i n e d t h e m e r c u r y c o n t e n t o f gallstones a n d
u r i n a r y calculi f r o m t h e a u t o p s i e d adults w h o had n o t b e e n involved in
o c c u p a t i o n a l m e r c u r y e x p o s u r e , a n d t h e f o l l o w i n g average values w e r e ob-
tained; gallstone 4.8 + 1.4 p p m , u r i n a r y calculus 2.6 + 1.5 p p m . T h e m e r c u r y
c o n t e n t o f t h e u r i n a r y calculus is a b o u t 1 0 0 0 t i m e s t h a t o f t h e n o r m a l
h u m a n urine.
U e d a and A o k i 77 investigated t h e m e t h y l m e r c u r y c o n t e n t o f t h e organs
of 3 adults w h o died s u d d e n l y and f o u n d less t h a n 0.02 p p m in t h e c e r e b r u m
and c e r e b e l l u m , 0 . 0 2 - - 0 . 0 3 p p m in t h e liver a n d k i d n e y . T h e m e t h y l m e r -
c u r y content of their hair ranged from 1.16--3.46 ppm.
Suzuki et al. 59 analyzed the mercury content of the red cells, plasma,
urine and hair of workers exposed to mercury vapour and found a larger
amount of inorganic mercury in the plasma than in the red cells, but alkyl
mercury was present in the red cells in much larger amounts than in the
plasma.

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(Jap. with Eng. summ.).
3 W.J. Brown and N. Yoshida, Organic mercurial encephalopathy -- An experimental
electron microscope study, Advan. Neurol. Sci., 9 (1965) 34--42.
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58
 7 N. Fukuhara, Ultrastructural changes in the cerebellar granular cell layers of experi-
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8 N. Fukuhara, K. Oguchi and T. Tsubaki, On the pathological alterations in the
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9 K. Furukawa, T. Suzuki and K. Tonomura, Decomposition of organic mercurial
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11 M. Futatsuka, S. Nomura, T. Matsushita, Y. Arimatsu, A. Ueda, J. Misumi, R. Tomio
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12 M. Harada, Latent Minamata disease, Kagahu, 41 (1971) 250--258 (Jap.).
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14 K. Hashizume, A. Yokota and S. Nanbu, The accumulation of ethyl mercury by algae
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15 K. Hirota, Distribution of methyl mercury compound in human brain and rat organs,
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16 N. Imura, E. Sukegawa, S.K. Pan, K. Nagao, J.Y. Kim, T. Kwan and T. Ukita,
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18 K. Irukayama, M. Fujiki and H. Nakamura, Treatment of the mother fluid containing
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19 K. Irukayama, M. Fujiki, S. Ohmori and H. Nakamura, Removal of mercury from
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20 K. Irukayama, M. Fujiki, S. Tajima and A. Ohmori, The transition of the mercury
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21 K. Irukayama, M. Fujiki, S. Tajima, S. Ohmori, H. Nakamura and S. Kuwahara,
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22 K. Irukayama and S. Kuwahara, Effect of mercurials administered to roosters on the
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23 K. Irukayama and S. Kuwahara, Studies on the combination of methyl mercury with
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59
26 T. Ishikura, N. Inoue and M. Yonaha, Toxicity of organic mercury compounds, I.
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27 T. Ishikura and M. Yonaha, Inhibition of erythrocyte cholinesterase by organic
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31 T. Kashimoto, S. Fukushima and S. Tsukamoto, Accumulation of methyl mercury in
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32 S. Katsuno and M. Kondo, Relationship between dose level of methyl mercury and
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37 S. Kitamura, K. Hayakawa, T. Shibata, Y. Iida and K. Sumino, Biological half-life
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38 S. Kitamura and K. Sumino, Synthesis of methyl mercury in photochemical reaction,
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39 S. Kitamura, K. Sumino, K. Hayakawa, T. Shibata and Y. Iida, Biological half-life
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40 S. Kitamura, K. Sumino, K. Hayakawa and Y. Taguchi, Accumulation of low concen-
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41 S. Kitamura, K. Sumino, I. Hirano and M. Taira, Formation and decomposition of
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45 H. Matsumoto and S. Yamaguchi, Studies on the transmural movements of mercury
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46 T. Miyagawa, M. Deshimaru, T. Inoue, A. Teraoka and N. Hotta, Electron-microsco-
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60
47 T. Muto and T. Suzuki, Analytical results of residual mercury in the Japanese storks,
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51 N. Ohta, M. Terai and J. Kosinaga, Studies on inorganic constituents in biological
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52 T. Sadakane, Studies on the toxicity of mercury, Report 2. Metabolism of ethylmer-
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55 T. Suzuki, K. Furukawa and K. Tonomura, Studies on the removal of inorganic
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63 S. Tajima, Studies on the formation of methyl mercury compounds, Report 3. On
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64 T. Takahashi, T. Kimura, Y. Sato, H. Shiraki and T. Ukita, Time-dependent distribu-
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61
 66 M. Takeda, K. Isobe, T. Nigo, T. Tanabe and I. Kawashiro, Metabolic fate of organo-
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68 Y. Takizawa, Investigation into the cause of outbreak of organic mercury poisoning
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70 M. Tatetsu, M. Takagi, T. Miyakawa, S. Sumiyoshi and M. Deshimaru, Experimental
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71 K. Teramoto, T. Tatewaki, A. Shinohara and H. Maruyama, Accumulation of methyl
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72 H. Tokuomi, Symposium on clinical observation on the public nuisances and agricul-
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73 K. Tonomura and F. Kanzaki, The reductive decomposition of organic mercurials by
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79 T. Ukita, Y. Takeda, Y. Sato and T. Takahashi, Distribution of Z°3Hg-mercury
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80 T. Ukita, Y. Takeda, T. Takahashi, M. Yoshikawa, Y. Sato and H. Shiraki, Distribu-
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