y;>.
 United States
 Environmental Protection
 Agency
Health Effects
Research Laboratory
Research Triangle Park NC 27711
 Research and Development
EPA/600/S1 -86/004 Nov. 1986
Project  Summary

Cadmium  Intake  Via  Oysters
and  Health   Effects in  New
Zealand:  Cadmium  Intake,
Metabolism and  Effects  in
People with a  High  Intake of
Oysters  in  New  Zealand

Joan McKenzie, Tord Kjellstrom, and Ram Sharma
  The aim of this study was to confirm
the high dietary intakes of cadmium
and other trace elements from oysters
in a population associated with the oys-
tering industry, and to determine (i) the
impact of those high intakes on cad-
mium concentrations in accessible tis-
sues of the study subjects and (ii) the
occurrence of health effects in the pop-
ulation resulting from their dietary ex-
posure to cadmium.
  Methods for the analysis of cadmium
in whole blood, urine and hair by flame-
less atomic absorption spectrophoto-
metry were established. The analysis of
Bluff oysters (Ostrea lutaria) confirmed
a high cadmium content (27 jig/g dry
wt); the content of other trace ele-
ments (zinc, copper, manganese, sele-
nium) was also determined, and differ-
ences in the proportions of the trace
elements compared with other species
of oysters and other shellfish found in
New Zealand were observed.
  Seventy-eight subjects participated;
from forty-eight of them samples of
faeces (3 day), blood, urine (overnight)
and hair were obtained both pre-
season and end-season (i.e., 6 months
later). Questionnaires on oyster intake
were administered; dietary and medi-
cal questionnaires were administered
at the end of the season when height,
weight and blood pressure were meas-
ured. The subjects were classified into
four categories of oyster intake with av-
erage consumptions being <0.5, 0.5-
<2,2-<6 and a6 dozen/week for Cate-
gories I, II, III and IV, respectively. The
faecal output of cadmium confirmed
the high intakes; e.g.. Category IV sub-
jects were ingesting about 250 |tg cad-
mium/day at the end of the season; cal-
culated intakes for Categories I, II and III
were 34 jig/d, 75 pg/d and 116 |ig/d,
respectively, at the end of the season.
Intakes of zinc were also elevated, and
selenium intake would have been dou-
bled for those subjects  consuming
many oysters.
 The concentration of cadmium  in
whole blood was higher in the smokers
than in the  non-smokers.  In the non-
smokers the increase in whole blood
cadmium due to oyster consumption
was only 1.2 ng/ml for Category IV.
Whole  blood selenium concentration
also was higher in Category IV subjects
but their serum zinc and  copper con-
centrations were unaffected. The con-
centrations of cadmium, zinc and B2-
microglobulin in the urine were
unaffected by oyster consumption;
there was no indication of glycosuria or
proteinuria that could have been at-
tributed to a high intake of cadmium.
Hair cadmium, zinc and copper also ap-
peared to be unaffected by oyster con-
sumption. There were no indications of
any medical problems that could have

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been attributed to a high cadmium in-
take;  although  the blood pressure of
Category III and especially Category IV
subjects was relatively higher than that
for Categories I and II and they also had
a greater body size.
  This Project  Summary was devel-
oped by EPA's Health Effects Research
Laboratory, Research Triangle Park, NC,
to announce key findings of the re-
search project that is fully documented
in a separate report of the same title
(see Project Report ordering informa-
tion at back).

Introduction
  During recent years there has been a
keen interest among researchers and
public health administrators in the toxi-
city of cadmium, with particular  refer-
ence to the possible increase of cad-
mium intake  due to increased use of
sewage  sludge  for soil treatment. The
risk of an actual increase in the cad-
mium intake has been well documented
and a major remaining question is
whether  such an increase is likely to
lead to any health effects.
  So far, only in Japan have population
groups with exceedingly  high cadmium
intakes via food been found. In the high
cadmium intake groups  in Japan, the
prevalence  of cadmium-induced
proteinuria might be as high as 50% or
more. Some studies in Japan demon-
strate clear dose-response relationships
and these data have been used to
analyse the dose-response at relatively
low dose levels. Calculations have been
supported by metabolic  models which
involve a number of assumptions, and
therefore uniform agreement  on the
health hazards involved  with slight in-
creases of average cadmium intake has
not been reached.
  Preliminary data from New Zealand
indicated that the oysters had such high
cadmium levels that a small  subgroup
of the population who  consumed a
large number of oysters annually,  could
have cadmium  intakes as high as the
affected populations in Japan. The
present study endeavoured to docu-
ment oyster intake in the  group with the
alleged high oyster consumption, their
cadmium intake and also  their cadmium
concentrations in various biological me-
dia such as blood, urine and hair. As the
oysters had relatively high levels  of se-
lenium,  zinc, copper  and manganese,
these trace  elements were also ana-
lyzed in most of the biological materials
collected.
  This New Zealand cadmium-exposed
group is the  only  one found outside
Japan with such high  cadmium intake
via food, and it is envisaged that further
studies of this group will give valuable
data for the explanation of the
metabolism as well as the toxic mecha-
nism of  cadmium.
  The aim of this study was to confirm
the high dietary intakes of cadmium and
other trace elements from oysters in a
population associated  with the oyster-
ing industry,  and to determine (i) the
impact  of those high  intakes on cad-
mium concentrations in accessible tis-
sues of the study subjects and (ii)the
occurrence of health effects in the popu-
lation resulting from their dietary expo-
sure to cadmium.
  This project covered an initial 18-
month period of which the specific aims
were the following:
(a) to develop methods for cadmium
   analysis in the tissues studied.
(b) to evaluate the cadmium content of
   various shellfish in New Zealand
   and the daily  cadmium intake in
   groups with  a high shellfish con-
   sumption.
(c) to  measure the  individual and
   group-average daily cadmium in-
   take of workers in a New Zealand
   oyster industry.
(d) to measure the interrelationship of
   cadmium concentrations (and of
   other trace metals) in serum, blood,
   urine and hair  in the group with a
   high cadmium intake from oysters
   and to measure the effect of sea-
   sonal variations on the cadmium in-
   take and tissue concentrations.
(e) to measure the occurrence of tubu-
   lar proteinuria  in the group with a
   high cadmium  intake.

Procedure
  About 70 male and female workers
are employed in the oyster canning in-
dustry and 50 male fishermen are in-
volved full time in the fishing during the
season  from March to August. In addi-
tion, there are 50 retired workers from
this industry still living in the same area.
Meetings were  held  with  the oyster
fishermen and canning workers in the
fishing  port of Bluff before the season
started  in 1981, and everyone was en-
couraged to take part in the study. As
the study involved the collection of
faeces, urine, blood and hair samples as
well as  keeping dietary records, etc., it
was not expected that everyone would
be willing to participate.
  The aim was to find a same-sized ref-
erence group of meat  industry slaugh-
termen with a low oyster intake, but it
turned out that many of these workers
in the area also had a high oyster intake,
and furthermore, it was even more diffi-
cult to convince them to take part as
they had no personal involvement with
the oyster industry.
  A number of people were found in
Bluff and in small communities adjacent
to Bluff with a low oyster intake but with
similar living conditions, etc., to the oys-
ter  fishermen;  these people were  in-
cluded in the group as a reference. All in
all,  76 people were  selected and they
were classified according to average
oyster consumption  during the season
into 4 groups. All these people lived in
the Bluff or Invercargill areas. An addi-
tional reference group for the Study of
blood cadmium and  urine cadmium
was found in the city of Dunedin.
  Samples were collected at two times,
and for a subgroup of 18 people at three
times. The first samples of faeces, urine,
blood and hair were  collected  in the
week before the season started  on
March 1, 1981. However the equipment
on the oyster fishing boats is checked in
the presence of a Ministry of Agriculture
and Fisheries Inspector in the few days
preceeding the opening of the season.
Since the  oysters reputedly taste better
at the beginning  of the season some
fishermen had already eaten a few oys-
ters in that week preceeding the official
opening of the season, and  their faecal
output of cadmium reflected that intake.
In the middle of the season in July 1981
additional samples of blood and a faecal
specimen were collected from 18 peo-
ple who were keen  to cooperate; they
also kept  a daily diary of oyster intake
from then until the next sampling. Fi-
nally, at the end of the season in August
1981 a full set of faeces, urine, blood
and hair samples were collected again,
as  well as an interview to obtain a di-
etary history and  a medical history.
  With this design of the study,  we
could evaluate the relationship between
oyster intake and  cadmium  intake on  a
quantitative basis and we could study
its time relationship, because at the be-
ginning of the season the  intake was
likely to be less than in the middle or the
end of the season.  The group studied
covered the age range 20-75 years and it
included 57 men and 19 women. Since
we were  describing mainly the short-
term relationship between cadmium in-
take and cadmium in tissues it was con-

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 sidered that  any age  effect on the
 cadmium concentration  in tissues was
 not likely to cause bias in the results.
   In order to evaluate the possible ef-
 fects of cadmium, urinary  beta-2-
 microglobulin  as well as total  protein-
 uria and  glycosuria were measured,
 blood pressure was measured and the
 medical history was recorded in an in-
 terview.
   Faeces were analyzed for cadmium,
 zinc, copper,  and manganese. Urine
 was analyzed  for pH, specific gravity,
 cadmium, zinc, creatinine, urea,  glu-
 cose, protein, and beta-2-microglobulin.
 Blood was analyzed for packed cell vol-
 ume, hemoglobin, cadmium, selenium,
 zinc, copper, and beta-2-microglobulin.
 Hair was  analyzed for cadmium, zinc,
 and copper. Dietary history was evalu-
 ated for energy, protein, calcium, zinc,
 and iron.


 Results and  Conclusions

  Methods for the estimation  of cad-
 mium in blood, urine and hair have
 been established , and to date appear to
 be reasonably accurate and  reliable.
 Further inter-laboratory comparisons
 will be carried  out.
  Bluff  oysters have  a high cadmium
 content; although all species of oysters
 have a relatively high cadmium content
 compared to most other foodstuffs, dif-
 ferent species show large differences in
 concentrations of cadmium as well as
 other trace elements. This is of great in-
 terest because a high consumption of
 different shellfish might reveal differ-
 ences in cadmium metabolism due to
 interactions among the elements.
  Intakes of cadmium in the population
 studies  were high. Analysis of faeces
 confirmed the high intakes of cadmium
 based on analyses of cadmium concen-
 tration in oysters and estimates of daily
 consumption. There was  a close agree-
 ment between  the observed content of
 cadmium, zinc and copper in faeces and
 estimated output. Some of the subjects
 with the highest oyster consumption
 had daily cadmium intakes greater than
 500 \j.g, which  are higher intakes than
 those shown to be associated with  a
 high incidence  of renal tubular damage
 in people exposed to contaminated rice
 in Japan. The New Zealand oyster con-
 sumers  also had intakes of zinc greater
than twice the normal New Zealand in-
take, and intakes of selenium about
twice a normal New Zealand intake. The
 limited data  available indicate that the
Japanese people with a high cadmium
exposure also had intakes of zinc and
selenium similar to those of the oyster
consumers.
  In spite of the very high intake of cad-
mium from oysters the concentration of
cadmium in whole blood was not in-
creased greatly in proportion to the in-
creased  intake. The data clearly show
increased blood cadmium  concentra-
tions due to smoking  in the four groups
with different levels of oyster consump-
tion. Among non-smokers the increase
in blood cadmium due to oyster  con-
sumption was only 1.2 ng/ml. There was
a good correlation between blood  cad-
mium  concentration  and oyster intake
at the beginning as well as at the end of
the oyster season. There were no ob-
served changes during the season or
between groups  in  urinary cadmium
output or in  hair cadmium concentra-
tion. There was a close correlation be-
tween  blood cadmium and  blood sele-
nium concentration, whereas neither
serum zinc nor serum copper concen-
tration increased with an  increasing
blood  cadmium concentration. There
were no differences in hair zinc or  cop-
per concentration.

  The  dipstick  proteinuria  and glyco-
suria tests did not show any indication
of cadmium-induced renal damage. The
frequency distribution of urinary beta-
2-microglobulin concentration was  sim-
ilar to "control groups" from other epi-
demiological  studies, and none of the
participants had a beta-2-microglobulin
concentration higher  than 250 (j.g/1  (ad-
justed to specific gravity 1.025).
  There  was a tendency for higher
blood pressures than expected  in the
groups with the highest oyster intakes.
This tendency was influenced by smok-
ing habits but an effect of cadmium on
blood pressure could  not be ruled out.
  Finally, the present study showed that
the cadmium  in Bluff oysters does not
appear to be absorbed to the extent that
is considered normal for other foods.
The mechanism for this diminished ab-
sorption could be interactions with sele-
nium and/or other trace  elements, but
could also be  unusual chemical specia-
tion in oysters compared to other food-
stuffs.  It  could also be that cadmium
from oysters is metabolised differently
from cadmium from other foods after it
has been absorbed.

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     Joan McKenzie and Ram Sharma are with University of Otago, Dunedin, New
       Zealand; and Tord Kjellstrom is with University of Auckland, Auckland, New
       Zealand.
     Normal Kowal is the EPA Project Officer (see below).
     The complete report, entitled "Cadmium Intake Via Oysters and Health Effects in
       New Zealand: Cadmium Intake, Metabolism and Effects in People with a High
       Intake of Oysters in New Zealand," (Order No. PB 86-219 144/AS; Cost:
       $16.95, subject to change) will be available only from:
             National Technical Information Service
             5285 Port Royal Road
             Springfield, VA 22161
             Telephone: 703-487-4650
     The EPA Project Officer can be contacted at:
             Health Effects Research Laboratory
             U.S. Environmental Protection Agency
             Research Triangle Park, NC27711
United States
Environmental Protection
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
Official Business
Penalty for Private Use $300
EPA/600/S1-86/004
        0000329   PS

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