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Cadmium Bioavailability in Food and Water

Data Plots

Statistics

Table of Studies

References

Questions

Cadmium Bioavailability
As part of an assessment of the relative bioavailability of cadmium in food and water, SRC collected data from published subchronic and chronic drinking water and feeding studies of rats. The data are grouped into data quality tiers and include estimates of the rates of accumulation of cadmium in kidney and liver. Data on the effects of cadmium on drinking water and food also were collected. A summary of the statistics of the data revealed that the bioavailability of cadmium in food and water, as assessed by kidney and liver accumulation, were not different.

Supported in part by EPA Cooperative Agreement CR 822761-01.

Reported in: Ruoff,
Contributors: William L. Ruoff, Gary L. Diamond, Susan F. Velazquez (TERA), William M. Stiteler and Daniel J. Gefell, W.L., G.L. Diamond, S.F. Velazquez, W.M. Stiteler and D. Gefell. 1994. Bioavailability of cadmium in food and water: A case study on the derivation of relative bioavailability factors for inorganics and their relevance to the reference dose. Reg. Toxicol. and Pharmacol. 20:139-160.

Data Quality Tiers

Tier 1
Data from studies in which identical exposure and analytical protocols were used to compare rats exposed to cadmium chloride in food or drinking water, and for which dosage was reported or could be accurately calculated. Tier 1 is usually considered to be the highest quality data for determining relative bioavailability, and is also usually the most scarce type of data.		 Tier 2
Data from studies in which rats were exposed to cadmium chloride in food and/or drinking water using similar protocols and for which dosage was reported or could be accurately calculated. The data was organized into groups within which experimental protocols were closely matched with respect to strain, sex, initial and final age, and initial and final body weights of the rats, and duration of treatment, and dosate. Tier 2 included Tier 1 data.
Tier 3
Data from studies in which rats were exposed to cadmium chloride in food or drinking water, from which dosage was reported or could be accurately calculated. No attempt was made to match experimental designs, therefore, the studies varied considerably with respect to rat strain, body weight, age and sex of rats, dose level, and duration of administration. However, the ranges of dosages from the two media were similar. Tier 3 included data from Tiers 1 and 2. 		Tier 4
Data from studies in which rats were exposed to cadmium chyloride in diet or drinking water, from which an exposure level (ppm) was reported. As with Tier 3, the studies in Tier 4 varied considerably with respect to strain, body weight, age and sex of rats, exposure level , and duration of administration; however, the ranges of dosages from the two media were similar. Tier 4 included data from Tiers 1, 2 and 3.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Data Tier Plots

The plots below represent the rate of accumulation of cadmium in the liver and kidney cortex of rats versus cadmium dosage in food or drinking water for the Tier data set listed.

Key to Plots
 = Food
= water
A plot = liver
B plot = kidney cortex

Tier 1 Data Set  
   
Tier 2 Data Set  
   
Tier 3 Data Set  
   
Tier 4 Data Set  
   
Drinking Water and Food Intake Plot
 Effects of exposure to cadmium in drinking water or food on intake of drinking water (A) or food (B), respectively. Controls were not exposed to cadmium. Data on drinking water intake are from thirteen studies; data on food intake are from eight studies.

Summary of Estimates of Relative Bioavailability
(Ff/w) of Cadmium Statistics

Statistical Methods
Data from Tiers 1, 2 and 3 were subjected to linear regression analysis to determine whether the rates of accumulation of cadmium in the liver and renal cortex, as a function of dosage, were significantly different (p<0.05), based on medium of administration. The slope of the regression lines relating tissue accumulation and dosage in food (mf) and water (mw) were used as indices of bioavailability of cadmium (F) in each medium; thus, the relative bioavailability or ratio of bioavailability of cadmium in food to that in water(Ff/w) was defined as the ratio of the slopes (mf/mw):

Data from Tiers 1, 2 and 3 were subjected to linear regression analysis to determine whether the rates of accumulation of cadmium in the liver and renal cortex, as a function of dosage, were significantly different (p<0.05), based on medium of administration. The slope of the regression lines relating tissue accumulation and dosage in food (mf) and water (mw) were used as indices of bioavailability of cadmium (F) in each medium; thus, the relative bioavailability or ratio of bioavailability of cadmium in food to that in water(Ff/w) was defined as the ratio of the slopes (mf/mw):

Ff/w = mf/mw Equation 1

The regression model that was used to estimate mf and mw is as follows (Mendenhall, 1968):

Y = ß0 +ß1X1 + ß2X2 +ß3X1X2 Equation 2

where:

Y = rate of accumulation of cadmium in tissue (µg/g wet weight/day)
X1 = 0 if the exposure medium is food, or 1 if the medium is water
X2 = dosage (mg/kg body weight/day)

If the medium of exposure is food (i.e., X1=0), Equation 2 reduces to:

Y = ß0 + ß2X2 Equation 3

and ß2 is the slope of the line relating tissue accumulation rate and dosage in food (mf). For exposures from water (i.e., X1=1):

Y = ß0 + ß1 + (ß2+ß3) · X2 Equation 4

ß2+ß3 is the slope of the line relating tissue accumulation rate and dosage from water (mw). Thus, ß3 is the difference between the slopes for water and food (mw-mf) and the ratio ß2/(ß2+ß3) is the ratio of the slopes, mf/mw, or Ff/w.

Two null hypotheses were tested. The first compared Ff/w with 1 (i.e., H0:Ff/w=1 vs. H1:Ff/w is not equal to 1. The null hypothesis in this case is equivalent to H0:mf/mw=1, which can be expressed in terms of model parameters as H0:ß3=0. The second hypothesis compared Ff/w with 0.5 (i.e., H0:Ff/w=0.5 vs. H1:Ff/w>0.5. The null hypothesis in this case is equivalent to H0:mf/mw=0.5, which can be expressed in terms of model parameters as H0:ß2=ß3. The null hypotheses were tested by a t-statistic (Mendenhall, 1968) and were rejected if the p-value was less than 0.05. The statistical analyses and data plots were developed with Statgraphics (version 5.0) (STSC, 1991).

Summary for Tiers 1, 2 and 3

T
I
E
R

Tissue		 mw
(95% CL)
(N)		 mf
(95% CL)
(N)
mw-mf
(95% CL)
Ff/w
(mf/mw)		 p
H0:Ff/w=1
H1:Ff/w not equal to 1		 p
H0:Ff/w=0.5
H1:Ff/w>0.5
1 Kidney 0.126
(0.108 - 0.145)
(30)		 0.126
(0.083 - 0.168)
(25)		 0.001
(-0.041 - 0.042)		 1.00 0.974 <0.005
2 Kidney 0.096
(0.073 - 0.118)
(35)		 0.104
(0.086 - 0.122)
(32)		 -0.008
(-0.044 - 0.027)		 1.08 0.642 <0.005
3 Kidney 0.061
(0.051 - 0.071)
(69)		 0.095
(0.088 - 0.101)
(55)		 -0.034
(-0.047 - -0.020)		 1.56 <0.001 <0.005
1 Liver 0.037
(0.029 - 0.044)
(30)		 0.044
(0.025 - 0.064)
(25)		 -0.007
(-0.026 - 0.011)		 1.19 0.420 <0.005
2 Liver 0.064
(0.044 - 0.083)
(32)		 0.059
(0.045 - 0.074)
(32)		 0.004
(-0.021 - 0.029)		 0.92 0.739 <0.025
3 Liver 0.067
(0.051 - 0.083)
(64)		 0.083
(0.078 - 0.089)
(55)		 -0.016
(-0.033 - 0.001)		 1.24 0.062 <0.005

mw and mf refer to the slopes the regression lines relating the rate of accumulation of cadmium in tissue (µg/g wet weight/day) to cadmium dosage (mg/kg body weight/day). The ratio of the slopes (mf/mw) is an estimate of relative bioavailability (Ff/w)

From Tier 1 Data

Dosage Tissue mw
(95% CL)
(N)		 mf
(95% CL)
(N)		 mw-mf
(95% CL)		 Ff/w
(mf/mw)		 p
H0:Ff/w=1
H1:Ff/w is not equal to 1
<0.15 Kidney 0.126
(0.108 - 0.145)
(30)		 0.126
(0.083 - 0.168)
(25)		 0.001
(-0.041 - 0.042)		 1.00 0.974
<0.1 Kidney 0.097
(0.084 - 0.109)
(25)		 0.122
(0.066 - 0.177)
(23)		 -0.008
(-0.078-0.028)		 1.26 0.350
<0.01 Kidney 0.080
(0.051 - 0.109)
(15)		 0.108
(0.066 - 0.150)
(11)		 -0.028
(-0.074 - -0.018)		 1.35 0.223
<0.15 Liver 0.037
(0.029 - 0.044)
(30)		 0.044
(0.025 - 0.064)
(25)		 -0.007
(-0.026 - 0.011)		 1.19 0.420
<0.1 Liver 0.025
(0.021 - 0.030)
(25)		 0.045
(0.018 - 0.071)
(23)		 -0.019
(-0.044 - 0.005)		 1.80 0.129
<0.01 Liver 0.024
(0.015 - 0.033)
(15)		 0.037
(0.021 - 0.053)
(11)		 -0.013
(-0.029 - 0.003)		 1.54 0.115

mw and mf refer to the slopes the regression lines relating the rate of accumulation of cadmium in tissue (µg/g wet weight/day) to cadmium dosage (mg/kg body weight/day). The ratio of the slopes (mf/mw) is an estimate of relative bioavailability (Ff/w). The dosage range was 0.00008-0.147 mg cadmium/kg/day.

From Tier 3 Data



Dosage

Tissue		 mw
(95% CL)
(N)		 mf
(95% CL)
(N)
mw-mf
(95% CL)
Ff/w
(mf/mw)		 p
H0:Ff/w=1
H1:Ff/w is not equal to 1
<14 Kidney 0.061
(0.051 - 0.071)
(69)		 0.095
(0.088 - 0.101)
(55)		 -0.034
(-0.047 - -0.020)		 1.56 <0.001
<4 Kidney 0.081
(0.064 - 0.099)
(62)		 0.094
(0.079 - 0.109)
(51)		 -0.013
(-0.038 - 0.012)		 1.16 0.298
<1 Kidney 0.240
(0.201 - 0.280)
(44)		 0.082
(0.074 - 0.090)
(36)		 0.159
(0.118 - 0.200)		 0.34 <0.001
<0.1 Kidney 0.143
(0.068 - 0.218)
(28)		 0.086
(0.036 - 0.137)
(23)		 0.057
(-0.031 - 0.144)		 0.60 0.199
<0.01 Kidney 0.080
(0.051 - 0.109)
(15)		 0.108
(0.066 - 0.150)
(11)		 -0.028
(-0.074 - 0.018)		 1.35 0.223
<14 Liver 0.067
(0.051 - 0.083)
(64)		 0.083
(0.078 - 0.089)
(55)		 -0.016
(-0.033 - 0.001)		 1.24 0.062
<4 Liver 0.046
(0.033 - 0.058)
(59)		 0.063
(0.051 - 0.076)
(51) 		-0.018
(-0.035 - 0.000)		 1.37 0.052
<1 Liver 0.089
(0.072 - 0.106)
(44)		 0.051
(0.043 - 0.058)
(36)		 0.038
(0.018 - 0.059)		 0.58 <0.001
<0.1 Liver 0.032
(0.021 - 0.043)
(28)		 0.032
(0.009 - 0.055)
(23)		 0.000
(-0.025 - 0.025)		 1.00 0.992
<0.01 Liver 0.024
(0.015 - 0.033)
(15)		 0.037
(0.021 - 0.053)
(11)		 -0.013
(-0.029 - 0.003)		 1.54 0.115

mw and mf refer to the slopes the regression lines relating the rate of accumulation of cadmium in tissue (µg/g wet weight/day) to cadmium dosage (mg/kg body weight/day). The ratio of the slopes (mf/mw) is an estimate of relative bioavailability (Ff/w). The dosage range was 0.00008-13.2 mg cadmium/kg/day.

Summary of Studies on Cadmium Bioavailability
Included in the Analysis

Study

 Rat Strain/Sex Media Duration (days) Tier(s)
Aughey et al., 1981 male Wistar water 7, 14, 28, 56, 84 4
Aughey et al., 1984 male Wistar water 21, 28, 42, 56, 70, 84, 168 4
Bernard et al., 1980 female Sprague-Dawley water 31, 70, 92, 122, 153, 183, 214, 336 4
Bernard et al., 1981 female Sprague-Dawley water 31, 70, 92, 122, 153, 183, 244 4
Bernard et al., 1983 female Sprague-Dawley water 70, 122, 183, 244, 305 4
Bernard et al., 1988 female Sprague-Dawley water 70 4
Bernard and Lauwerys, 1981 female Sprague-Dawley water 122 4
Buhler et al., 1981 male and female Wistar water or food 7, 14, 28, 56, 84 1-4
Cousins et al., 1977 male Sprague-Dawley food 98 2-4
Decker et al., 1958 male and female Sprague-Dawley water 183, 365 3-4
Eakin et al., 1980 male OSU Brown rats food 28, 56, 84, 112 4
Fingerle et al., 1982 male and female Sprague-Dawley water 574, 644 3-4
Fowler et al., 1975 male Charles River water 42, 84 3-4
Groten et al., 1991 male Wistar food 28, 56 2-4
Itokawa et al., 1974 male Wistar water 120 2-4
Jamall et al., 1989 male Sprague-Dawley water 49 2-4
Kajikawa et al., 1981 male Wistar water 8, 112, 168, 224, 280 4
Kawamura et al., 1978 female Wistar water 90 4
Kotsonis and Klaassen, 1978 male Sprague-Dawley water 21, 42, 84, 168 2-4
Larsson and Piscator, 1971 female Sprague-Dawley water 28, 56 4
Loeser and Lorke, 1977 male and female Wistar food 28, 56, 84 2-4
Maji and Yoshida, 1974 male and female Wistar food 13 3-4
Mangler et al., 1988 female Sprague-Dawley water 183, 365, 549 2-4
Nation et al., 1984 male Sprague-Dawley food 57 4
Pribble and Weswig, 1973 male and female brown rats water or food 549 4
Prigge et al., 1977 male Wistar water 52 4
Prigge, 1978 female Wistar water 90 4
Rosenberg and Kappas,1991 male Sprague-Dawley water 5 3-4
Sakata et al., 1988 male Wistar water 12, 26, 50, 100 4
Shaikh et al., 1989 male Wistar water 730 4
Tewari et al., 1986 male albino ITRC food 15, 30, 45, 60 4
Uthe and Chou, 1980 female Sprague-Dawley food 90 2-4
Viau et al., 1984 female Sprague-Dawley water 365 4
Washko and Cousins, 1975 male Sprague-Dawley water 56 2-4
Zenick et al., 1982 male Sprague-Dawley water 75 2-4

Cadmium References

Abe, Y., Tanaka, S., and Itokawa, Y. (1972). Japan. J. Hyg. 28, 243.
 (In Japanese with abstract in English).

Agency for Toxic Substances and Disease Registry (ATSDR) (1992). Toxicological Profile for Cadmium. U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA.

Andersen, O., Sch„fer, L., and Nielsen, J.B. (1992). Diet composition determines the bioavailability of cadmium for intestinal uptake. IARC Science Publ. 114, 173-182.

Aughey, E., Scott, R., Fell, G.S., and Cunningham, C. (1981). Rat blood cadmium levels and early renal lesions. In Trace Element Metabolism in Man and Animals (J.M. Gawthorne and C.L. White, Eds.), pp. 453-456. Australian Academy of Science, Canberra, 1981.

Aughey, E., Fell, G.S., Scott, R., and Black, M. (1984). Histopathology of early effects of oral cadmium in the rat kidney. Environ. Health Perspect. 15, 153-161.

Baranski, B., and Sitarek, K. (1987). Effect of oral and inhalation exposure to cadmium on the estrous cycle in rats. Toxicol. Lett. (Amst) 36, 267-274.

Bernard, A.M., and Lauwerys, R.R. (1981). The effects of sodium chromate and carbon tetrachloride on the urinary excretion and tissue distribution of cadmium in cadmium-pretreated rats. Toxicol. Appl. Pharmacol. 57, 30-38.

Bernard, A., Goret, A., Buchet, J.P., Roels, H., and Lauwerys, R. (1980). Significance of cadmium levels in blood and urine during long-term exposure to cadmium. J. Toxicol. Environ. Health 6, 175-184.

Bernard, A., Lauwerys, R., and Gengoux, P. (1981). Characterization of the proteinuria induced by prolonged oral administration of cadmium in female rats. Toxicology 20, 345-357.

Bernard, A., Viau, C., and Lauwerys, R. (1983). Renal handling of human á2-microglobulin in normal and cadmium-poisoned rats. Arch. Toxicol. 53, 45-57.

Bernard, A.M., de Russis, R., Amor, A.O., and Lauwerys, R.R. (1988). Potentiation of cadmium nephrotoxicity by acetaminophen. Arch. Toxicol. 63, 291-294.

Borzelleca, J.F., Clarke, E.C., and Conde, L.W., Jr. (1989). Short-term toxicity (1 and 10 days) of cadmium chloride in male and female rats: Gavage and drinking water. J. Am. Coll. Toxicol. 8, 377-404.

Buhler, D.R., Wright, D.C., Smith, K.L., and Tinsley, I.J. (1981). Cadmium absorption and tissue distribution in rats provided low concentrations of cadmium in food or drinking water. J. Toxicol. Environ. Health 8, 185-197.

Carmignani, M., and Boscolo, P. (1984). Cardiovascular responsiveness to physiological agonists of male rats made hypertensive by long-term exposure to cadmium. Sci. Total Environ. 34, 19-33.

Cousins, R.J., Squibb, K.S., Feldman, S.L., de Bari, A., and Silbon, B.L. (1977). Biomedical responses of rats to chronic exposure to dietary cadmium fed in ad libitum and equalized regimes. J. Toxicol. Environ. Health 2, 929-943.

Decker, L.E., Byerrum, R.U., Decker, C.F., Hoppert, C.A., and Langham, R.F. (1958). Chronic toxicity studies. I. Cadmium administered in drinking water to rats. Arch. Ind. Health 18, 228-231.

Eakin, D.J., Schroeder, L.A., Whanger, P.D., and Weswig, P.H. (1980). Cadmium and nickel influence on blood pressure, plasma renin, and tissue mineral concentrations. Am. J. Physiol. 238, E53-E61.

Ellis, K.J., Vartsky, D., Zanzi, I., and Cohn, S.H. (1979). Cadmium: In vivo measurement in smokers and nonsmokers. Science 205, 323-325.

Engstr”m, B., and Nordberg, G. (1978). Effects of milk diet on gastrointestinal absorption of cadmium in adult mice. Toxicology.
9, 195-203.

Fingerle, H., Fischer, G., and Classen, H.G. (1982). Failure to produce hypertension in rats by chronic exposure to cadmium. Food Chem. Toxicol. 20, 301-306.

Flanagan, P.R., McLellan, J.S., Haist, J., Cherian, G., Chamberlain, M.J., and Valberg, L.S. (1978). Increased dietary cadmium absorption in mice and human subjects with iron deficiency. Gastroenterology 7, 841-846.

Foulkes, E.C. (1986). Absorption of cadmium. In Handbook of Experimental Pharmacology (Foulkes, E.C., Ed.), Vol. 80, pp. 75-100. Springer-Verlag, Berlin.

Fowler, B.A. (1975). The morphologic effects of chronic cadmium administration on the renal vasculature of rats given low and normal calcium diets. Toxicol. Appl. Pharmacol. 34, 233-252.

Fox, M.R. (1983). Cadmium bioavailability. Fed. Proc. 42, 1726-1729.

Friberg, L. (1984). Cadmium and the kidney. Environ. Health Perspect. 54, 1-11.

Friberg, L., Piscator, M., Nordberg, G.F., and Kjellstrom, T. (1974). Cadmium in the Environment. CRC Press, Boca Raton, FL. (As cited in Friberg et al., 1985).

Friberg, L, Elinder, C.G., Kjellstrom, T., and Nordberg, G.F. (1985). Cadmium and Health: A Toxicological and Epidemiological Appraisal, Vol.I and II. CRC Press, Inc., Boca Raton, FL.

Groten, J.P., Sinkeldam, E.J., Luten, J.B., and van Bladeren, P.J. (1990). Comparison of the toxicity of inorganic and liver-incorporated cadmium: A 4-wk feeding study in rats. Food Chem. Toxicol. 28, 435-442.

Groten, J.P., Sinkeldam, E.J., Muys, T., Luten, J.B., and van Bladeren, P.J. (1991). Interaction of dietary Ca, P, Mg, Mn, Cu, Fe, Zn, and Se with the accumulation and oral toxicity of cadmium in rats. Food Chem. Toxicol. 29, 249-258.

Itokawa, Y., Abe, T., Tabei, R., and Tanaka, S. (1974). Renal and skeletal lesions in experimental cadmium poisoning. Arch. Environ. Health 28, 149-154.

Jamall, I.S., Nail, M., Sprowls, J.J., and Trombetta, L.D. (1989). A comparison of the effects of dietary cadmium on heart and kidney antioxidant enzymes: Evidence for the greater vulnerability of the heart to cadmium toxicity. J. Appl. Toxicol. 9, 339-345.

James, H.M., M. Hilburn and J.A. Blair. (1985). Effects of meals and meal times on the uptake of lead from the gastrointestinal tract in humans. Hum. Toxicol. 4, 401-407.

Kajikawa, K., Nakanishi, I., and Kuroda, K. (1981). Morphological changes of the kidney and bone of rats in chronic cadmium poisoning. Exp. Molec. Pathol. 34, 9-24.

Kanisawa, M., and Schroeder, H.A. (1969). Renal arteriolar changes in hypertensive rats given cadmium in drinking water. Exp. Molec. Pathol. 10, 81-98.

Kawamura, J., Yoshida, O, Nishino, K., and Itokawa, Y. (1978). Disturbances in kidney functions and calcium and phosphate metabolism in cadmium-poisoned rats. Nephron. 20, 101-110.

Kello D., and Kostial K. (1977). Influence of age and milk diet on cadmium absorption from the gut. Toxicol. Appl. Pharmacol. 40, 277-282.

Kitamura, S. (1972). Cadmium absorption and accumulation (mainly about humans) (in Japanese). Kankyo Hoken Rep. 11. p. 42. Japanese Public Health Association. (As cited in Friberg et al., 1985).

Koizumi, N. (1975). Title not available. Jpn. J. Hyg. 30, 300. (In Japanese with abstract in English). (As cited in Tsuchiya, 1978).

Kotsonis, F.N., and Klaassen, C.D. (1978). The relationship of metallothionein to the toxicity of cadmium after prolonged oral administration to rats. Toxicol. Appl. Pharmacol. 46, 39-54.

Larsson, S.E., and Piscator M. (1971). Effect of cadmium on skeletal tissue in normal and calcium-deficient rats. Israel J. Med. Sci. 7,
495-498.

Loeser, E., and Lorke, D. (1977). Semichronic oral toxicity of cadmium. 1. Studies on rats. Toxicology 7, 215-224.

Machemer, L., and Lorke, D. (1981). Embryotoxic effect of cadmium on rats upon oral administration. Toxicol. Appl. Pharmacol. 58, 438-443.

Maji, T., and Yoshida, A. (1974). Therapeutic effect of dietary iron and ascorbic acid on cadmium toxicity of rats. Nutr. Rep. Int. 10, 139-149.

Mangler, B., Fischer, G., Classen, H.G., and Th”ni, H. (1988). The induction and reversibility of cadmium-induced nephropathy in rats: Quantitative analytical and histological studies. Trace Elem. Med. 5,
143-149.

McLellan, J.S., Flanagan, P.R., Chamberlain, M.J., and Valberg, L.S. (1978). Measurement of dietary cadmium absorption in humans. J. Toxicol. Environ. Health 4, 131-138.

Mendenhall, W. (1968). Introduction to Linear Models and the Design and Analysis of Experiments. Duxbury Press, Belmont, CA. CRC Press, Inc., Boca Raton, FL. pp. 148-150.

Mushak, P. (1991). Gastro-intestinal absorption of lead in children and adults: Overview of biological and biophysico-chemical aspects. Chem. Spec. Bioavail. 324, 87-104

Nation, J.R., Bourgeois, A.E., Clark, D.E., Baker, D.M., and Hare, M.F. (1984). The effects of oral cadmium exposure on passive avoidance in the adult rat. Toxicol. Lett. 20, 41-47.

Newton, D., Johnson, P., Lally, A.E., et al. (1984). The uptake by man of cadmium ingested in crab meat. Hum. Toxicol. 3, 23-28.

Nogawa, K., Kobayashi, E., and Konishi, F. (1981). Comparison of bone lesions in chronic cadmium intoxication and vitamin D deficiency. Environ. Res. 24, 233-249.

Ohanian, E.V., Iwai, J., Leiti, G., and Tuthill, R. (1978). Genetic influence on cadmium induced hypertension. Am. J. Physiol. 235, H385-H391.

Pond, W.G., and Walker, E.F., Jr. (1975). Effect of dietary Ca and Cd level of pregnant rats on reproduction and on dam and progeny tissue mineral concentrations (38606). Proc. Soc. Exp. Biol. Med. 148, 665-668.

Pribble, H.J., and Weswig, P.H. (1973). Effects of aqueous and dietary cadmium on rat growth and tissue uptake. Bull. Environ. Contam. Toxicol. 9, 271-274.

Prigge, E. (1978). Early signs of oral and inhalative cadmium uptake in rats. Arch. Toxicol. 40, 231-247.

Prigge, E., Baumert, H.P., and Muhle, H. (1977). Effects of dietary and inhalation cadmium on hemoglobin and hematocrit in rats. Bull. Environ. Contam. Toxicol. 17, 585-590.

Rabar, I., and Kostial, K. (1981). Bioavailability of cadmium in rats fed various diets. Arch. Toxicol. 47, 63-66.

Rahola, T., Aaran, R.-K., and Miettinen, J.K. (1972). Half-time studies of mercury and cadmium by whole body counting. In Assessment of Radioactive Contamination in Man, IAEA-SM-150/13, pp. 553-562. International Atomic Energy Agency, Unipublisher, New York.

Rosenberg, D.W., and Kappas, A. (1991). Induction of heme oxygenase in the small intestinal epithelium: A response to oral cadmium exposure. Toxicology 67, 199-210.

Sakata, S., Iwami, K., Enoki, Y., Kohzuki, H., Shimizu, S., Matsuda, M., and Moriyama, T. (1988). Effects of cadmium on in vitro and in vivo erythropoiesis: Erythroid progenitor cells (CFU-E), iron, and erythropoietin in cadmium-induced iron deficiency anemia. Exp. Hematol. 16, 581-587.

Shaikh, Z.A., and Smith, J.C. (1980). Metabolism of orally ingested cadmium in humans. Toxicol. Lett. (Amst) 0 (Spec. Issue 1), 81.

Shaikh, Z.A., K.M. Harnett, Perlin, S.A., and Hu