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Gastrointestinal absorption of different compounds of 115mcadmium and the effect of different concentrations in the rat
ENVIRONMENTAL
RESEARCH
6, 159-164
(1973)
Gastrointestinal Absorption 1 15T”Cadmium and
of Different Compounds the Effect of Different
Concentrations WELLINGTON Enoironmental Research
in the Rat
MOORE, JR., JEHRY F. STAHA, AND WALDEN
Protection Agency, Center, Erxironmental
Ofice of Research and Monitoring, Toxicology Research Llicision, Received
of
Afcgrlst
C. CHOCKER
National Cincinnati,
Environmental Ohio 45268
1, 1972
The absorption and retention of three different compounds of ““‘“cadmium and the effects of variations in concentration were studied in female rats. After a single oral did not significantly influence dose, the chloride, sulfate, and acetate forms of “““‘Cd the absorption, retention, or distribution of the ““““Cd in the tisslles. TIE only organs containing significant amounts of “““Cd were the liver, kidney, and gastrointestinal tract. Increases in concentration of cadmium resulted in more cadmium being absorbed from the gastrointestinal tract, although the amount absorbed was not proportional to the increase in concentration.
Along with the rapid expausion in the use of cadmium and its compounds in industrial processes,there has arisen the problem of increased environmental contamination (Flick, Kraybill, and Dimitroff, 1971). Cadmium is obtained as a by-product in the refining of zinc and other metals. These industries and those associated with refining, machining, and electroplating of cadmium materials serve’ as possible emission sources for environmental pollution. Cadmium is also used in the manufacture of pesticides and fertilizers, and both the production and use of these products increase the levels of cadmium in the environment. Based on present information, cadmium is not considered as an essential element for the maintenance of life in man or animals (Schroeder et al., 1967). Several investigators have studied the fate of a single oral dose of cadmium and have reported that only a small percentage is absorbed. Decker et ul. (1957) gave about 6.6 mg/kg of “XXNO, to rats by stomach tube and found 95-99% in the stomach, gut, and feces after 8 and 24 hr. Cotzias, Borg, and Selleck (1961) dosed mice with 40 &Ii “‘“CdCl, by intubation and found, after 4 hr, 0.523%absorption. Richmond et ~7. (1966) reported a mean retention after a few days of about 1% (range 0.53%) in mice after administration of “‘“Cd by intubation. Miller et al. (1968) gave goats “WdCl, (0.04-0.06 mg/Cd per goat) in gelatin capsules and found that more than 90%of the dose had been excreted in the feces after 14 days. He estimated total body retention at 0.3-0.4% of the given dose. The purpose of this study is to investigate what effect, if any, different chemical compounds of cadmium might have upon gastrointestinal absorption, retention, and tissue distribution. The effect of different concentrations of cadmium upon absorption is also reported. 159 Copyright All rights
@ 1973 by Academic Press, of reproduction in any form
Inc. reserved.
160
MOORE,
STARA,
MATERIALS
AND
AND
CROCKER
METHODS
Female rats of the COBS strain, weighing 150-180 g, were used in this study. All animals were maintained on a regular diet and water ad lib. With the exception of one group, all animals were fasted 24 hr before dosing. The chloride, sulfate, and acetate forms of “sfncadmiunl, which had specific activities of 0.835, 0.815, and 0.815 mCi/mg cadmium, respectively, were used in the study. The rats were divided into three groups of 48 animals and each animal in a group was given by stomach tube a single dose of 50 ,&i in 0.5 ml distilled water of one of the “?zadmium compounds. Immediately after dosing, whole body counts were made on 10 animals selected randomly. The animals were counted daily for the first few days and then every other day for the duration of the experiment. A 200channel gamma spectrometer with a 5-in. NaI (TL) crystal was used for wholebody counting. At intervals of 1, 2, 4, 8, 16, and 32 days after dosing, eight animals from each group were sacrificed for tissue samples. In order to determine if fasting had any effect upon ll”“Lcadmium absorption, 10 nonfasted rats were given 1’5mcadmium chloride via stomach tube. For the assessment of the influence of different concentrations of total cadmium upon gastrointestinal absorption, two additional levels of cadmium chloride (0.75 mg Cd/animal, 7.5 mg Cd/animal) were studied using the same procedures. RESULTS
sulfate, and “%adThe retention rates for ll%adrnium chloride, “““cadmium mium acetate after a single dose given via stomach tube are shown in Fig. 1. The results indicated that the type of cadmium compound did not significantly influence the gastrointestinal absorption and retention of “““Cd although the amount of llSrnCd retained after administration of “:‘““cadmium acetate was somewhat higher. There was an initial rapid clearance during the first 4 days, repre-
250 * 40 30.$
:........-.:;:a3cop o- - - -oCdC12 .
f-
i:zn UBI Oc 0’P I * 2%H; 6’ %\o f0
5432-
D
*
----___ I . -;----a.---” ------k3 1)
-*--------/
1
FIG.
( CH,CO)‘,
1.
Whole-body and “““CdCl,.
retention
of “““Cd
after
...--
. --F-.2--
a single
1
intragastric
:
dose of “““CdSO,,
llbmCd-
G.
I.
ABSORPTION
OF
DIFFERENT
161
llZWLCd COMPOUNDS
senting the passage of nonabsorbed cadmium through the intestinal tract. Fasting the animals for 24 hr did not significantly influence absorption or the time required compounds through the gastrointestinal tract. In the for transit of the “-Wd group of rats which was not fasted prior to dosing, 55.0% of the ‘l”mcadmium chloride was retained at the end of 24 hr and 3.01% at ‘the end of 4 days, while in the fasted group, the values were 55.6% and 3.170, respectively. Thus, after 6 days, between 2.7% and 3.5% of the ilZ~Ql was absorbed when given as cadmium chloride, cadmium sulfate, or cadmium acetate. Analysis of the sIow component for each of the retention curves indicated a when administered as biological half-life of between 35 and 57 days for “‘“‘Cd the chloride, sulfate, or acetate. The linear least-squares equation for the slow component of each retention curve was 3.22-0.36X for cadmium chloride, 2.27.021X for cadmium sulfate, and 3.88-.041X for cadmium acetate, where the values in the equation represent the intercept minus the value for the slope times a given day after dosing. Radioactive counts of the feces and urine showed that most of the l’“Wd was eliminated via the feces and only an extremely small amomlt was found in the urine. Twenty-four hours after administration of the “““‘cadmium acetate, 52.1% of the initial dose was present in the 24-hr feces sample and 0.025% of the initial dose was in the 24-hr urine sample. Six days after dosing, 0.22% and 0.013% was found in 24-hr samples of feces and urine, respectively. After the first few days, there was a very low continuous rate of excretion of lln’tiCd in the feces during the entire period of study. At 32 days postexposurc 0.026% of the initial dose was present in a 24-hr feces sample. Tissue samples werr taken from different organs and analyzed for ‘““‘Cd. After a single oral dose, the only tissues containing significant amounts of “““‘Cd were the gastrointestinal tract, liver, and kidney. No radioactive cadmium was detected in any of the blood samples. The peak concentration of ll”“Cd in the gastrointestinal tract occurred during the first 24 hr followed by a rapid decline. Maximum
Cadmium l)uodenllm Cadmium Cadmium Cadmium Liver Cadmium Cadmium Cadmium Kidney Cadmium Cadmium Cadmium
compound
1
”
rhloride sulfate a&&e
4
s
16
0.19 0.15 0.16
0.19 0.13 0.16
0 13 0.12 0.12
0.11 0 061 0.083
0.11 0.073 0.074
0.084 0.078 0. on0
0.0“7 I 0.094 0.031
chloride sIllfate a&ate
0. I 3 0.31 0.1s
chloride su1fat.e acetate
0.061 0.081 0.077
0.27 0 “0 0.25
162
MOORE,
STARA,
AND
CROCKER
-c--O.06 ms Cd --_ ..-- 0.75mg Cd -v--7.50 m g Cd
1
FIG. 2.
’
’ 4
’
’ 8
-T1 1 -1 12 Days,
Effect of total concentration
b16 After
1-._ I I _._ I 20 24 Dosing
1-i-P 28
of “5mCdCl, upon
. 32
whole-body
retention.
concentrations in the liver and kidney were reached 48 hr after exposure with a very slow decline in concentration thereafter. The type of cadmium compound did not affect significantly the concentration or distribution of 115WLCd in the tissues.The percentage of the initia1 dose per gram of tissue found in the duodenum, liver, and kidney at different time intervals after exposure is given in Table 1. The influence of different concentrations of cadmium chloride upon the absorption of 11511Cd from the gastrointestinal tract is shown in Fig. 2. Examination of Fig. 2 reveals that at low concentrations, the absorption of llzWd was increased while at higher concentrations, ‘the absorption of 116Wd was decreased. These results reflected the increasing dilution of the tracer ‘15”Cd by the higher concentrations of total Cd, such that the specific activity of the absorbed Cd decreased with increasing concentrations of Cd. In fact, the data showed that the total amount of Cd absorbed increased with increasing concentrations, since a lo-fold increase in total Cd reduced 115Wd retention by only approximately onehalf. The mean amount of Cd in the livers and kidneys (/(g/g wet sample) for the three concentrations is shown in Table 2. The animals receiving the highest concentration had the greatest amount of Cd in the liver and kidney, although the increase was not proportional to the increase in concentration. TABI&: Trssr-IC
CONCICZTTIL
\TIONK
2 OF C
WMIUM
,~g Cd/g ~~.---~ Ammmt 0.060 0.75 7.5
of Cd give11 mg Cd/animal mg Cd/animal mg Cd/animal
Kidney .0731 “.mo .77”3
wet weight, Liver 102.5 : 7723 1.5645
G.
I.
ABSORPTION
OF
DIFFERENT
“‘n’Cd
COMPOUNDS
163
DISCUSSION
For these cadmium compounds, the results show that only 3-5% of a given oral dose of cadmium is absorbed with considerable variation among animals. Other reports on mice and rats give an absorption rate of about 2-3% for Cd chloride, which is comparable. Cadmium absorption in animals is also influenced by certain dietary factors, such as the amount of cadmium, calcium, vitamin D, zinc, and protein in the diet. The level of cadmium in the diet is an obvious variable which affects the percentage of absorption of cadmium as demonstrated in this study. Larsson and Piscator (1971) have folund that liver and kidneys of rats on a low calcium diet contained about 50%more Cd than the same organs from rats on a high calcium diet. Suzuki et al. (1969) reported that the passage of cadmium through the digestive tract was slower in rats fed a low-calcium diet as compared to those fed a high-calcium diet. Vitamin D has been shown to increase intestinal absorption of cadmium in rnchitic chickens. Worker and Migikowsky (1961) also observed an increase in uptake of cadmium in chickens fed a lowcalcium and low-vitamin D diet. Studies in our laboratory have shown an increase in cadmium absorption and retention in rats maintained on a diet deficient in zinc. Suzuki et al. (1969) f ound that rats fed a low-protein diet had considerably higher whole-body retention of cadmium than those fed a highprotein diet (range 5-14 vs range 3-10). At present, experimental data on the absorption of cadmium by man is not available. so extrapolation from animal data ImiSt be asctl. The data presented here indicate that the probable average absorption rate in man would be around 2-X? with consider&c variation. Estimations for man based on the intalw of cadmium over a 50-year period and the body burden? found at autopsies indicate an average absorption of somewhere between 3 and 8%. These values are not much different from those reported for animals, especially when consideration is given to the different factors which influence cadmium absorption. Cadmium absorption was increased considerably by low intake of calcium and protein in animals; it appears that similar effect would occ’ur in man. Whcntvcr human data become available on cadmium absorption, these factors mllst be also considered. REFERENCES C., BOIK:, L). C., AND S~LLECK, R. ( 1961). Virtual ahscnce of turnover in metabolism: ‘“’ Cd studies in the molw. Amer. J. Pl~ysiol. 201, 927-930. DECKER, C. F., BTERRUE~I, R. II., AND HAPPEW, C. A. (1957). A stlldy of the distribution and retention of cadmium-115 in the albino rat. Arch. Rioch. Biophys. 66, 140-145. FLICK, D. F., KRAYBILL, II. F., AND DIKTIWFF, J. M. (1971). Toxic effects of cadmium: A review. Environ. Res. 4, 71-83. Fnnxnc, L., PISCATOR, M., ANO NOIWHEIK;, C.. ( 1971 ). Cadmium in the environment. A toxicological and epidemiological appraisal. Chapter 4: Metabo!ism. The Karolinska Institute, Stockholm. MILI~ER, W. J., BLACKMON, II. M., AND RIARTIN, W. F. (1968). Cadmium ahsorption, excretion and tissue distribution following single tracer oral and intravenous doses in young goats. J. Dairy Sci. 51, 18.36-18.39. RICHHOND, C. R., FINDLAY, J. S., ANI) LONDON, J. F. ( 1966). Whole-body retention of cadmium-109 by mice following oral, intraperitoneal and intravenous administration. U. S. At. Energy Comm., Univ. of Calif. Los Alamos Sci. Lab. LA-3GlO-MS, pp. 195-200. COTZIAS,
cadmium
G.
164
MOORE,
STARA,
AND
CROCKER
H. A., NASON, A. P., TIPTON, I. H., AND BALASSA, J. J. (1967). Essential trace in man: Zinc. Relation to environmental cadmium. J. Chronic Dis. 20, 179-210. SUZUKI, S., TAQUCHI, T., AND YOHOHASHI, G. (1969). Dietary factors influencing upon the retention rate of orally administered “““CdCL in mice. Arch. Id. Health 7, 155-162. WORKER, N. A., AND MIGIKOWSKY, B. B. ( 1961). Effect of vitamin D on the utilization of zinc, cadmium and mercury in the chick. J. Nutr. ‘75,222-224. SCHROEDER,
metals
RESEARCH
6, 159-164
(1973)
Gastrointestinal Absorption 1 15T”Cadmium and
of Different Compounds the Effect of Different
Concentrations WELLINGTON Enoironmental Research
in the Rat
MOORE, JR., JEHRY F. STAHA, AND WALDEN
Protection Agency, Center, Erxironmental
Ofice of Research and Monitoring, Toxicology Research Llicision, Received
of
Afcgrlst
C. CHOCKER
National Cincinnati,
Environmental Ohio 45268
1, 1972
The absorption and retention of three different compounds of ““‘“cadmium and the effects of variations in concentration were studied in female rats. After a single oral did not significantly influence dose, the chloride, sulfate, and acetate forms of “““‘Cd the absorption, retention, or distribution of the ““““Cd in the tisslles. TIE only organs containing significant amounts of “““Cd were the liver, kidney, and gastrointestinal tract. Increases in concentration of cadmium resulted in more cadmium being absorbed from the gastrointestinal tract, although the amount absorbed was not proportional to the increase in concentration.
Along with the rapid expausion in the use of cadmium and its compounds in industrial processes,there has arisen the problem of increased environmental contamination (Flick, Kraybill, and Dimitroff, 1971). Cadmium is obtained as a by-product in the refining of zinc and other metals. These industries and those associated with refining, machining, and electroplating of cadmium materials serve’ as possible emission sources for environmental pollution. Cadmium is also used in the manufacture of pesticides and fertilizers, and both the production and use of these products increase the levels of cadmium in the environment. Based on present information, cadmium is not considered as an essential element for the maintenance of life in man or animals (Schroeder et al., 1967). Several investigators have studied the fate of a single oral dose of cadmium and have reported that only a small percentage is absorbed. Decker et ul. (1957) gave about 6.6 mg/kg of “XXNO, to rats by stomach tube and found 95-99% in the stomach, gut, and feces after 8 and 24 hr. Cotzias, Borg, and Selleck (1961) dosed mice with 40 &Ii “‘“CdCl, by intubation and found, after 4 hr, 0.523%absorption. Richmond et ~7. (1966) reported a mean retention after a few days of about 1% (range 0.53%) in mice after administration of “‘“Cd by intubation. Miller et al. (1968) gave goats “WdCl, (0.04-0.06 mg/Cd per goat) in gelatin capsules and found that more than 90%of the dose had been excreted in the feces after 14 days. He estimated total body retention at 0.3-0.4% of the given dose. The purpose of this study is to investigate what effect, if any, different chemical compounds of cadmium might have upon gastrointestinal absorption, retention, and tissue distribution. The effect of different concentrations of cadmium upon absorption is also reported. 159 Copyright All rights
@ 1973 by Academic Press, of reproduction in any form
Inc. reserved.
160
MOORE,
STARA,
MATERIALS
AND
AND
CROCKER
METHODS
Female rats of the COBS strain, weighing 150-180 g, were used in this study. All animals were maintained on a regular diet and water ad lib. With the exception of one group, all animals were fasted 24 hr before dosing. The chloride, sulfate, and acetate forms of “sfncadmiunl, which had specific activities of 0.835, 0.815, and 0.815 mCi/mg cadmium, respectively, were used in the study. The rats were divided into three groups of 48 animals and each animal in a group was given by stomach tube a single dose of 50 ,&i in 0.5 ml distilled water of one of the “?zadmium compounds. Immediately after dosing, whole body counts were made on 10 animals selected randomly. The animals were counted daily for the first few days and then every other day for the duration of the experiment. A 200channel gamma spectrometer with a 5-in. NaI (TL) crystal was used for wholebody counting. At intervals of 1, 2, 4, 8, 16, and 32 days after dosing, eight animals from each group were sacrificed for tissue samples. In order to determine if fasting had any effect upon ll”“Lcadmium absorption, 10 nonfasted rats were given 1’5mcadmium chloride via stomach tube. For the assessment of the influence of different concentrations of total cadmium upon gastrointestinal absorption, two additional levels of cadmium chloride (0.75 mg Cd/animal, 7.5 mg Cd/animal) were studied using the same procedures. RESULTS
sulfate, and “%adThe retention rates for ll%adrnium chloride, “““cadmium mium acetate after a single dose given via stomach tube are shown in Fig. 1. The results indicated that the type of cadmium compound did not significantly influence the gastrointestinal absorption and retention of “““Cd although the amount of llSrnCd retained after administration of “:‘““cadmium acetate was somewhat higher. There was an initial rapid clearance during the first 4 days, repre-
250 * 40 30.$
:........-.:;:a3cop o- - - -oCdC12 .
f-
i:zn UBI Oc 0’P I * 2%H; 6’ %\o f0
5432-
D
*
----___ I . -;----a.---” ------k3 1)
-*--------/
1
FIG.
( CH,CO)‘,
1.
Whole-body and “““CdCl,.
retention
of “““Cd
after
...--
. --F-.2--
a single
1
intragastric
:
dose of “““CdSO,,
llbmCd-
G.
I.
ABSORPTION
OF
DIFFERENT
161
llZWLCd COMPOUNDS
senting the passage of nonabsorbed cadmium through the intestinal tract. Fasting the animals for 24 hr did not significantly influence absorption or the time required compounds through the gastrointestinal tract. In the for transit of the “-Wd group of rats which was not fasted prior to dosing, 55.0% of the ‘l”mcadmium chloride was retained at the end of 24 hr and 3.01% at ‘the end of 4 days, while in the fasted group, the values were 55.6% and 3.170, respectively. Thus, after 6 days, between 2.7% and 3.5% of the ilZ~Ql was absorbed when given as cadmium chloride, cadmium sulfate, or cadmium acetate. Analysis of the sIow component for each of the retention curves indicated a when administered as biological half-life of between 35 and 57 days for “‘“‘Cd the chloride, sulfate, or acetate. The linear least-squares equation for the slow component of each retention curve was 3.22-0.36X for cadmium chloride, 2.27.021X for cadmium sulfate, and 3.88-.041X for cadmium acetate, where the values in the equation represent the intercept minus the value for the slope times a given day after dosing. Radioactive counts of the feces and urine showed that most of the l’“Wd was eliminated via the feces and only an extremely small amomlt was found in the urine. Twenty-four hours after administration of the “““‘cadmium acetate, 52.1% of the initial dose was present in the 24-hr feces sample and 0.025% of the initial dose was in the 24-hr urine sample. Six days after dosing, 0.22% and 0.013% was found in 24-hr samples of feces and urine, respectively. After the first few days, there was a very low continuous rate of excretion of lln’tiCd in the feces during the entire period of study. At 32 days postexposurc 0.026% of the initial dose was present in a 24-hr feces sample. Tissue samples werr taken from different organs and analyzed for ‘““‘Cd. After a single oral dose, the only tissues containing significant amounts of “““‘Cd were the gastrointestinal tract, liver, and kidney. No radioactive cadmium was detected in any of the blood samples. The peak concentration of ll”“Cd in the gastrointestinal tract occurred during the first 24 hr followed by a rapid decline. Maximum
Cadmium l)uodenllm Cadmium Cadmium Cadmium Liver Cadmium Cadmium Cadmium Kidney Cadmium Cadmium Cadmium
compound
1
”
rhloride sulfate a&&e
4
s
16
0.19 0.15 0.16
0.19 0.13 0.16
0 13 0.12 0.12
0.11 0 061 0.083
0.11 0.073 0.074
0.084 0.078 0. on0
0.0“7 I 0.094 0.031
chloride sIllfate a&ate
0. I 3 0.31 0.1s
chloride su1fat.e acetate
0.061 0.081 0.077
0.27 0 “0 0.25
162
MOORE,
STARA,
AND
CROCKER
-c--O.06 ms Cd --_ ..-- 0.75mg Cd -v--7.50 m g Cd
1
FIG. 2.
’
’ 4
’
’ 8
-T1 1 -1 12 Days,
Effect of total concentration
b16 After
1-._ I I _._ I 20 24 Dosing
1-i-P 28
of “5mCdCl, upon
. 32
whole-body
retention.
concentrations in the liver and kidney were reached 48 hr after exposure with a very slow decline in concentration thereafter. The type of cadmium compound did not affect significantly the concentration or distribution of 115WLCd in the tissues.The percentage of the initia1 dose per gram of tissue found in the duodenum, liver, and kidney at different time intervals after exposure is given in Table 1. The influence of different concentrations of cadmium chloride upon the absorption of 11511Cd from the gastrointestinal tract is shown in Fig. 2. Examination of Fig. 2 reveals that at low concentrations, the absorption of llzWd was increased while at higher concentrations, ‘the absorption of 116Wd was decreased. These results reflected the increasing dilution of the tracer ‘15”Cd by the higher concentrations of total Cd, such that the specific activity of the absorbed Cd decreased with increasing concentrations of Cd. In fact, the data showed that the total amount of Cd absorbed increased with increasing concentrations, since a lo-fold increase in total Cd reduced 115Wd retention by only approximately onehalf. The mean amount of Cd in the livers and kidneys (/(g/g wet sample) for the three concentrations is shown in Table 2. The animals receiving the highest concentration had the greatest amount of Cd in the liver and kidney, although the increase was not proportional to the increase in concentration. TABI&: Trssr-IC
CONCICZTTIL
\TIONK
2 OF C
WMIUM
,~g Cd/g ~~.---~ Ammmt 0.060 0.75 7.5
of Cd give11 mg Cd/animal mg Cd/animal mg Cd/animal
Kidney .0731 “.mo .77”3
wet weight, Liver 102.5 : 7723 1.5645
G.
I.
ABSORPTION
OF
DIFFERENT
“‘n’Cd
COMPOUNDS
163
DISCUSSION
For these cadmium compounds, the results show that only 3-5% of a given oral dose of cadmium is absorbed with considerable variation among animals. Other reports on mice and rats give an absorption rate of about 2-3% for Cd chloride, which is comparable. Cadmium absorption in animals is also influenced by certain dietary factors, such as the amount of cadmium, calcium, vitamin D, zinc, and protein in the diet. The level of cadmium in the diet is an obvious variable which affects the percentage of absorption of cadmium as demonstrated in this study. Larsson and Piscator (1971) have folund that liver and kidneys of rats on a low calcium diet contained about 50%more Cd than the same organs from rats on a high calcium diet. Suzuki et al. (1969) reported that the passage of cadmium through the digestive tract was slower in rats fed a low-calcium diet as compared to those fed a high-calcium diet. Vitamin D has been shown to increase intestinal absorption of cadmium in rnchitic chickens. Worker and Migikowsky (1961) also observed an increase in uptake of cadmium in chickens fed a lowcalcium and low-vitamin D diet. Studies in our laboratory have shown an increase in cadmium absorption and retention in rats maintained on a diet deficient in zinc. Suzuki et al. (1969) f ound that rats fed a low-protein diet had considerably higher whole-body retention of cadmium than those fed a highprotein diet (range 5-14 vs range 3-10). At present, experimental data on the absorption of cadmium by man is not available. so extrapolation from animal data ImiSt be asctl. The data presented here indicate that the probable average absorption rate in man would be around 2-X? with consider&c variation. Estimations for man based on the intalw of cadmium over a 50-year period and the body burden? found at autopsies indicate an average absorption of somewhere between 3 and 8%. These values are not much different from those reported for animals, especially when consideration is given to the different factors which influence cadmium absorption. Cadmium absorption was increased considerably by low intake of calcium and protein in animals; it appears that similar effect would occ’ur in man. Whcntvcr human data become available on cadmium absorption, these factors mllst be also considered. REFERENCES C., BOIK:, L). C., AND S~LLECK, R. ( 1961). Virtual ahscnce of turnover in metabolism: ‘“’ Cd studies in the molw. Amer. J. Pl~ysiol. 201, 927-930. DECKER, C. F., BTERRUE~I, R. II., AND HAPPEW, C. A. (1957). A stlldy of the distribution and retention of cadmium-115 in the albino rat. Arch. Rioch. Biophys. 66, 140-145. FLICK, D. F., KRAYBILL, II. F., AND DIKTIWFF, J. M. (1971). Toxic effects of cadmium: A review. Environ. Res. 4, 71-83. Fnnxnc, L., PISCATOR, M., ANO NOIWHEIK;, C.. ( 1971 ). Cadmium in the environment. A toxicological and epidemiological appraisal. Chapter 4: Metabo!ism. The Karolinska Institute, Stockholm. MILI~ER, W. J., BLACKMON, II. M., AND RIARTIN, W. F. (1968). Cadmium ahsorption, excretion and tissue distribution following single tracer oral and intravenous doses in young goats. J. Dairy Sci. 51, 18.36-18.39. RICHHOND, C. R., FINDLAY, J. S., ANI) LONDON, J. F. ( 1966). Whole-body retention of cadmium-109 by mice following oral, intraperitoneal and intravenous administration. U. S. At. Energy Comm., Univ. of Calif. Los Alamos Sci. Lab. LA-3GlO-MS, pp. 195-200. COTZIAS,
cadmium
G.
164
MOORE,
STARA,
AND
CROCKER
H. A., NASON, A. P., TIPTON, I. H., AND BALASSA, J. J. (1967). Essential trace in man: Zinc. Relation to environmental cadmium. J. Chronic Dis. 20, 179-210. SUZUKI, S., TAQUCHI, T., AND YOHOHASHI, G. (1969). Dietary factors influencing upon the retention rate of orally administered “““CdCL in mice. Arch. Id. Health 7, 155-162. WORKER, N. A., AND MIGIKOWSKY, B. B. ( 1961). Effect of vitamin D on the utilization of zinc, cadmium and mercury in the chick. J. Nutr. ‘75,222-224. SCHROEDER,
metals