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Effect of rat's diet on 85Sr, 115mCd, and 203Hg absorption in suckling rats
ENVIRONMENTAI~
RESEARCH
25, 281-285 (1981)
Effect of Rat’s Diet on 85Sr, l15%d, and 203Hg Absorption in Suckling Rats K. KOSTIAL, I.,$IMONOVI~,*
I. RABAR, AND M. LANDEKA
Received July IO. 1980 Six-day-old suckling rats were artificially fed over 8 hr with cow‘s milk or rat’s diet labeled with ““Sr, “““‘Cd. or 203Hg. The whole-body radioactivity was determined in a double-crystal scintillation counter every 24 hr over a 6-day period. Rat‘s diet caused a reduction in the whole-body retention of all radioisotopes which was highest for :‘ISHg and lowest for %r. All sucklings were killed 6 days after the radioisotope administration and the radioactivity was determined in the carcass and in the gut. Rat’s diet reduced carcass retention by about 107 for ?Sr, and two and three times for “““‘Cd and “uaHg, respectively. Rat’s diet also reduced gut retention by about 20% for “YSr. two times for “““‘Cd and eight times for ‘““Hg. It is concluded that dietary factors are partly responsible for the high metal absorption in sucklings. This specially applies to mercury because rat’s diet caused a considerable reduction in the whole-body retention of this metal primarily by decreasing its gut retention.
INTRODUCTION
It is known that sucklings retain a much higher fraction of orally administered metals than adults. This high absorption in neonates seems to be a general feature of metal metabolism (toxic and essential) in several animal species and in humans (Nordberg et (11.. 1978). One of the possible roles was attributed to milk, since the high absorption in neonates suddenly decreases at the time of weaning and since older animals on milk diet also show increased absorption of several metals (Kostial et nl., 1978). However, morphological and functional features specific for neonates like the nonspecific pinocytotic absorption of macromolecules (Shiraishi and Ichikawa, 1972) are also maintained only until the time of weaning. Weaning is therefore a period of major morphological, functional, as well as nutritional changes for the neonate. The purpose of this work was to evaluate the relative significance of nutritional changes for the absorption of metals in sucklings. We therefore artificially fed sucklings with rat’s diet 1 to 2 weeks before the natural weaning period and determined the retention of orally administered Yjr, Ils”lCd, and zn3Hg. The results indicate that diet plays an important role in metal absorption in neonates. MATERIALS
AND METHODS
The experiment was performed on 6-day-old suckling rats which were kept in litters of six (reduced to this number within 24 hr after birth). They were artif& cially fed over 8 hr with either cow’s milk (0.4 ml) administered by a dropper (Kostial ef al.. 1967) or with rat’s diet (0.2 g) ground to particles and administered
282
KOSTIAL
ET
AL.
with a glass spoon. There were 18 litters in the experiment. In each litter three sucklings were artificially fed on milk (controls) and three on rat’s diet. The animals were divided into three groups of 6 litters which received s5Sr (0.5 &i), llsmCd (5 &i), or 203Hg (1 &i) in milk or in rat’s diet over the 8-hr artificial feeding period. All radioisotopes were supplied from the Radiochemical Centre, Amersham, England. The specific activity of l15Vd and *03Hg was about 0.5 mCi/mg Cd or Hg, and 85Sr was practically carrier free. The whole-body radioactivity was determined immediately after the end of the artificial feeding (this value was taken as 100% of the dose) and then every 24 hr over the 6-day experimental period. At the end of the experiment the rats were killed by excess of ether and the radioactivity was determined in the carcass (whole body after removal of the total intestinal tract distal to the diaphragm) and gut (the total intestinal tract, contents included). The retention of radioactive cadmium and mercury was also determined in the liver and kidneys. Radioactivity measurements of the whole body, carcass, and gut were performed in a double-crystal scintillation counter (Tobor, Nuclear Chicago), by setting whole samples in a counting chamber between the crystals. Radioactivity measurements of the liver and kidneys were performed in a well-type scintillation counter (Nuclear Chicago), The results were corrected for radioactive decay and geometry of the samples. They were expressed as percentage of the dose and presented as arithmetic means and standard error of the means. The r test was used to determine the level of statistical significance between the groups. TABLE 1 OF ““Sr, ‘15”ICd, AND ‘““Hg IN SUCKLING ARTIFICIALLY FED MILK OR RAT’S DIET
RETENTION
WHOLE-BODY
I I>“Cd
%r
Milk (18)”
Rat’s diet (17)
Milk/ rat’s diet
Milk
1
90.13” 0.74’
82.91 1.24
2
85.48 1.18
77.95 1.21
3
81.13 1.09 78.91 1.04
74.65 1.34 73.60 1.22
5
76.73 1.02
69.99 1.15
6
73.19 1.18
67.00 1.12
Days after administration
4
Nore. Data are given (P < 0.001). 0 Number of animals b Arithmetic means. p SEM.
as percentage in parentheses.
RATS
‘O:‘Hg Milk/ rat’s diet
Milk
(18)
Rat’s diet (18)
1.09
80.28 1.65
55.67 1.47
1.10
56.40 2.74
34.92 1.61
41.98 4.07 41.40 3.59
27.94 1.48 24.77 1.62
1.10
38.27 3.57
22.92 1.50
1.09
35.19 3.10
21.60 1.31
1.09 1.07
oral dose.
All differences
(18)
Rat’s diet (17)
Milk/ rat’s diet
1.44
85.73 1.72
37.69 3.03
2.27
1.62
74.19 1.47
17.08 2.07
4.34
68.26 1.16 66.84 1.28
13.08 1.73 11.17 1.38
1.67
57.80 1.32
9.32 0.96
6.20
1.63
47.70 1.19
7.66 0.84
6.23
1.50 1.67
between
groups
are highly
5.22 5.98
significant
Sr,
Cd,
AND
Hg ABSORPTION
IN
SUCKLING
283
RATS
RESULTS
All whole-body retention values of 85Sr. 115”rCd, and 2”3Hg were lower in the sucklings which received radioactive isotopes with rat’s diet than in control. milk-fed animals. The highest difference between the groups was observed for z”3Hg and the lowest for x5Sr. Differences in the body retention which occurred 1 to 2 days after oral administration of the radioisotopes were maintained throughout the experiment (Table 1 and Fig. 1). The carcass and organ retentions were also reduced in the sucklings on rat’s diet-they were about 10% lower for X5Sr and about two and three times lower for 1’5”tCd and ?03Hg, respectively (Table 2). The gut retention was also lower in the sucklings treated with rat’s diet than in controls. The highest reduction was observed for f”3Hg (about eight times) indicating that the high difference in the whole-body retention of mercury between the groups (about six times-Table 1) was partly due to a greatly reduced gut retention in the sucklings which received rat’s diet.
100
o
milk
0
rat’s
diet
60
60
1
1
days FIG. or rat’s
1. Whole-body diet (0).
retention
of”“Sr.
L
2
3
after
administration
“S”‘Cd
and
‘““Hg
in suckling
5
6
rats
artificially
fed
cow’s
milk
(0)
284
KOSTIAL
ET AL.
TABLE
2
CARCASS.
GUT, AND ORGAN RETENTION z”:rHg IN SUCKLING RATS FED MILK
Milk No. of animals Carcass Gut
18 74.24 + 1.O@ 0.16 ” 0.01
Rat’s diet
17 67.93 i- 1.25 0.13 t 0.01
OF “%r, ““‘“Cd, OR RAT’S DIET
Factor: milk/rat’s diet
AND
Level of significance, PC
1.t 1.2
0.001 0.05
1.9 1.5 1.9 1.5
0.001 0.05 0.001 0.001
3.4 8.4 3.3 3.2
0.001 0.001 0.001 0.001
“““‘Cd
No. of animals Carcass Gut Liver Kidneys No. of animals Carcass Gut Liver Kidneys
12.63 21.41 5.48 0.48
18 ” 1.08 ? 2.87 4 0.69 2 0.03
6.70 14.04 2.92 0.33
18 ” 0.25 -c 1.20 r 0.16 2 0.02
‘“W 10.43 39.80 2.81 I .38
18 2 0.46 ‘- 1.08 2 0.10 _t 0.07
3.08 4.75 0.86 0.43
17 k 0.23 t 0.66 k 0.09 2 0.03
Note. Percentage dose 6 days after oral administration. milk or rat’s diet labeled with radioisotopes. u Arithmetic means + SEM.
Sucklings were artificially fed for 8 hr with
DISCUSSION
Nutritional factors are known to influence the absorption and retention of several metals (Nordberg et al., 1978; Fox, 1979; Bremner, 1979). However, this does not necessarily apply to sucklings since the neonatal age is a specific period for cation absorption. It is a period when no differences in the intestinal absorption between cations with and without an active transport mechanism have been observed; in which the absorption of homeostatically controlled cations and the competitive mechanism for cation absorption are different than in adults; and when some metals have a higher retention and a longer residence time in the gut than in adults (Kostial et al., 1979a). In spite of these differences we found that rat’s diet administered to sucklings 1 to 2 weeks before normal weaning decreased metal absorption. The absorption values were still much higher than those usually observed in adult rats. However, under our experimental conditions sucklings consumed only small amounts of rat’s diet over the 8-hr artificial feeding period and also they were returned to their mothers, i.e., to milk, immediately after the end of the radioisotope administration. Therefore the reabsorption during the enteral recycling of the metals was not affected by rat’s diet but by milk. Differences found between the groups are therefore likely to be underestimated under our experimental conditions.
Sr, Cd,
AND
Hg ABSORPTION
IN SUCKLING
RATS
285
There are several possible explanations for the effect of rat’s diet on metal absorption. The higher trace element content is not likely to be one of them, since we recently found that the addition of iO0 ppm Fe, 50 ppm Zn, 200 ppm Mn, and 20 ppm Cu to milk caused almost no changes in the absorption and retention of orally administered cadmium and mercury in sucklings (Kostial et al., 1980). Rat’s diet could accentuate the extrusion of cells from the villi where the metal is deposited in sucklings (Inaba and Lengemann, 1972; Sasser and Jarboe. 19771, but under our experimental conditions it is more likely that it primarily prevented metal deposition in the gut. This specially applies to cadmium and mercury which show a high retention in the “gut compartment” after oral administration in sucklings (Kostial et cl/.. 1979a). Mercury from gut seems to be specially accessible to interaction with the luminal content since a change of diet several days after a single oral administration of *03Hg causes considerable changes in the gut and carcass retention of this metal (Kostial et nl., 1979b). All this indicates that some ligands from the rat’s diet have a higher affinity for metals than the ligands involved in the first step of intestinal absorption, i.e.. in the transfer of metal from the intestinal lumen into the mucosa. It can be concluded that dietary factors participate in the high absorption of metals in neonates and that further studies into the absorption mechanism in sucklings in relation to diet are needed. ACKNOWLEDGMENT This work was partially supported under a research grant from the U.S. Environmental Agency.
Protection
REFERENCES Bremner, 1. (1979). The toxicity of cadmium. zinc, and molybdenum and their effects on copper metabolism. Proc. Nutr. SW. 38, 235-242. Forbes, G. B.. and Reina. J. C. (1972). Effect of age on gastrointestinal absorption (Fe, Sr, Pb) in the rat. J. Nlrrr. 102, 647-652. Fox. M. R. S. (1979). Nutritional influences on metal toxicity: Cadmium as a model toxic element. En\~irc~rl. Hvnlrh Prr.sprct. 29, 95% 104. Inaba, J.. and Lengemann, F. W. (1972). Intestinal uptake and whole body retention of “‘Cc by suckling rats. Hmlrh Phys. 22, 169- 175. Kostial, K., Kello. D., Jugo, S.. Rabar, I., and Maljkovic, T. (1978). Influence of age on metal metabolism and toxicity. Environ. Hralth Prrsprct. 25, 81-86. Kostial. K.. Rabar, I.. Blanusa, M., and Landeka, M. (1979a). Effect of age on heavy metal absorption. Proc.. Nlrtr. SM. 38, 251-256. Kostial. K.. Rabar, I., and Ciganovic, M. (1980). The influence of trace elements on cadmium and mercury absorption in suckling rats. In “Abstracts, International Conference on Industrial and Environmental Xenobiotics: Biotransformation and Kinetics, May 27-30. Prague.” p. 37. Kostial, K.. Rabar, I.. Ciganovid. M., and Simonovic, I. (1979b). Effect of milk on mercury absorption and gut retention in rats. Err//. Environ. Conform. Taxicd. 23. 566-S71. Kostial, K., Simonovic. I., and PiSonic. M. (1967). Effect of calcium and phosphates on gastrointestinal absorption of strontium and calcium in newborn rats. Nrrrrrrr (Lr~rnlon) 215, 1181, 1182. Nordberg, G. F., Fowler, B. A., Friberg, L., Jernelov, A., Nelson. N., Piscator, M.. Sanstead, H. H.. Vestal. J.. and Vouk. V. B. (1978). Factors influencing metabolism and toxicity of metals: A consensus report. En~~iuon. Hen/t11 Persped. 25, 3-41. Sasser. L. B.. and Jarboe, G. E. (1977). Intestinal absorption and retention ofcadmium in neonatal rat. To.ric~cd. Appl. Pharmcrcwl. 41, 423-431. Shiraishi, Y.. and Ichikawa. R. (1972). Absorption and retention of ““Ce and ““Zr-S’Nb in newborn. juvenile. and adult rats. Hurrlril Phs. 22. 373-378.
RESEARCH
25, 281-285 (1981)
Effect of Rat’s Diet on 85Sr, l15%d, and 203Hg Absorption in Suckling Rats K. KOSTIAL, I.,$IMONOVI~,*
I. RABAR, AND M. LANDEKA
Received July IO. 1980 Six-day-old suckling rats were artificially fed over 8 hr with cow‘s milk or rat’s diet labeled with ““Sr, “““‘Cd. or 203Hg. The whole-body radioactivity was determined in a double-crystal scintillation counter every 24 hr over a 6-day period. Rat‘s diet caused a reduction in the whole-body retention of all radioisotopes which was highest for :‘ISHg and lowest for %r. All sucklings were killed 6 days after the radioisotope administration and the radioactivity was determined in the carcass and in the gut. Rat’s diet reduced carcass retention by about 107 for ?Sr, and two and three times for “““‘Cd and “uaHg, respectively. Rat’s diet also reduced gut retention by about 20% for “YSr. two times for “““‘Cd and eight times for ‘““Hg. It is concluded that dietary factors are partly responsible for the high metal absorption in sucklings. This specially applies to mercury because rat’s diet caused a considerable reduction in the whole-body retention of this metal primarily by decreasing its gut retention.
INTRODUCTION
It is known that sucklings retain a much higher fraction of orally administered metals than adults. This high absorption in neonates seems to be a general feature of metal metabolism (toxic and essential) in several animal species and in humans (Nordberg et (11.. 1978). One of the possible roles was attributed to milk, since the high absorption in neonates suddenly decreases at the time of weaning and since older animals on milk diet also show increased absorption of several metals (Kostial et nl., 1978). However, morphological and functional features specific for neonates like the nonspecific pinocytotic absorption of macromolecules (Shiraishi and Ichikawa, 1972) are also maintained only until the time of weaning. Weaning is therefore a period of major morphological, functional, as well as nutritional changes for the neonate. The purpose of this work was to evaluate the relative significance of nutritional changes for the absorption of metals in sucklings. We therefore artificially fed sucklings with rat’s diet 1 to 2 weeks before the natural weaning period and determined the retention of orally administered Yjr, Ils”lCd, and zn3Hg. The results indicate that diet plays an important role in metal absorption in neonates. MATERIALS
AND METHODS
The experiment was performed on 6-day-old suckling rats which were kept in litters of six (reduced to this number within 24 hr after birth). They were artif& cially fed over 8 hr with either cow’s milk (0.4 ml) administered by a dropper (Kostial ef al.. 1967) or with rat’s diet (0.2 g) ground to particles and administered
282
KOSTIAL
ET
AL.
with a glass spoon. There were 18 litters in the experiment. In each litter three sucklings were artificially fed on milk (controls) and three on rat’s diet. The animals were divided into three groups of 6 litters which received s5Sr (0.5 &i), llsmCd (5 &i), or 203Hg (1 &i) in milk or in rat’s diet over the 8-hr artificial feeding period. All radioisotopes were supplied from the Radiochemical Centre, Amersham, England. The specific activity of l15Vd and *03Hg was about 0.5 mCi/mg Cd or Hg, and 85Sr was practically carrier free. The whole-body radioactivity was determined immediately after the end of the artificial feeding (this value was taken as 100% of the dose) and then every 24 hr over the 6-day experimental period. At the end of the experiment the rats were killed by excess of ether and the radioactivity was determined in the carcass (whole body after removal of the total intestinal tract distal to the diaphragm) and gut (the total intestinal tract, contents included). The retention of radioactive cadmium and mercury was also determined in the liver and kidneys. Radioactivity measurements of the whole body, carcass, and gut were performed in a double-crystal scintillation counter (Tobor, Nuclear Chicago), by setting whole samples in a counting chamber between the crystals. Radioactivity measurements of the liver and kidneys were performed in a well-type scintillation counter (Nuclear Chicago), The results were corrected for radioactive decay and geometry of the samples. They were expressed as percentage of the dose and presented as arithmetic means and standard error of the means. The r test was used to determine the level of statistical significance between the groups. TABLE 1 OF ““Sr, ‘15”ICd, AND ‘““Hg IN SUCKLING ARTIFICIALLY FED MILK OR RAT’S DIET
RETENTION
WHOLE-BODY
I I>“Cd
%r
Milk (18)”
Rat’s diet (17)
Milk/ rat’s diet
Milk
1
90.13” 0.74’
82.91 1.24
2
85.48 1.18
77.95 1.21
3
81.13 1.09 78.91 1.04
74.65 1.34 73.60 1.22
5
76.73 1.02
69.99 1.15
6
73.19 1.18
67.00 1.12
Days after administration
4
Nore. Data are given (P < 0.001). 0 Number of animals b Arithmetic means. p SEM.
as percentage in parentheses.
RATS
‘O:‘Hg Milk/ rat’s diet
Milk
(18)
Rat’s diet (18)
1.09
80.28 1.65
55.67 1.47
1.10
56.40 2.74
34.92 1.61
41.98 4.07 41.40 3.59
27.94 1.48 24.77 1.62
1.10
38.27 3.57
22.92 1.50
1.09
35.19 3.10
21.60 1.31
1.09 1.07
oral dose.
All differences
(18)
Rat’s diet (17)
Milk/ rat’s diet
1.44
85.73 1.72
37.69 3.03
2.27
1.62
74.19 1.47
17.08 2.07
4.34
68.26 1.16 66.84 1.28
13.08 1.73 11.17 1.38
1.67
57.80 1.32
9.32 0.96
6.20
1.63
47.70 1.19
7.66 0.84
6.23
1.50 1.67
between
groups
are highly
5.22 5.98
significant
Sr,
Cd,
AND
Hg ABSORPTION
IN
SUCKLING
283
RATS
RESULTS
All whole-body retention values of 85Sr. 115”rCd, and 2”3Hg were lower in the sucklings which received radioactive isotopes with rat’s diet than in control. milk-fed animals. The highest difference between the groups was observed for z”3Hg and the lowest for x5Sr. Differences in the body retention which occurred 1 to 2 days after oral administration of the radioisotopes were maintained throughout the experiment (Table 1 and Fig. 1). The carcass and organ retentions were also reduced in the sucklings on rat’s diet-they were about 10% lower for X5Sr and about two and three times lower for 1’5”tCd and ?03Hg, respectively (Table 2). The gut retention was also lower in the sucklings treated with rat’s diet than in controls. The highest reduction was observed for f”3Hg (about eight times) indicating that the high difference in the whole-body retention of mercury between the groups (about six times-Table 1) was partly due to a greatly reduced gut retention in the sucklings which received rat’s diet.
100
o
milk
0
rat’s
diet
60
60
1
1
days FIG. or rat’s
1. Whole-body diet (0).
retention
of”“Sr.
L
2
3
after
administration
“S”‘Cd
and
‘““Hg
in suckling
5
6
rats
artificially
fed
cow’s
milk
(0)
284
KOSTIAL
ET AL.
TABLE
2
CARCASS.
GUT, AND ORGAN RETENTION z”:rHg IN SUCKLING RATS FED MILK
Milk No. of animals Carcass Gut
18 74.24 + 1.O@ 0.16 ” 0.01
Rat’s diet
17 67.93 i- 1.25 0.13 t 0.01
OF “%r, ““‘“Cd, OR RAT’S DIET
Factor: milk/rat’s diet
AND
Level of significance, PC
1.t 1.2
0.001 0.05
1.9 1.5 1.9 1.5
0.001 0.05 0.001 0.001
3.4 8.4 3.3 3.2
0.001 0.001 0.001 0.001
“““‘Cd
No. of animals Carcass Gut Liver Kidneys No. of animals Carcass Gut Liver Kidneys
12.63 21.41 5.48 0.48
18 ” 1.08 ? 2.87 4 0.69 2 0.03
6.70 14.04 2.92 0.33
18 ” 0.25 -c 1.20 r 0.16 2 0.02
‘“W 10.43 39.80 2.81 I .38
18 2 0.46 ‘- 1.08 2 0.10 _t 0.07
3.08 4.75 0.86 0.43
17 k 0.23 t 0.66 k 0.09 2 0.03
Note. Percentage dose 6 days after oral administration. milk or rat’s diet labeled with radioisotopes. u Arithmetic means + SEM.
Sucklings were artificially fed for 8 hr with
DISCUSSION
Nutritional factors are known to influence the absorption and retention of several metals (Nordberg et al., 1978; Fox, 1979; Bremner, 1979). However, this does not necessarily apply to sucklings since the neonatal age is a specific period for cation absorption. It is a period when no differences in the intestinal absorption between cations with and without an active transport mechanism have been observed; in which the absorption of homeostatically controlled cations and the competitive mechanism for cation absorption are different than in adults; and when some metals have a higher retention and a longer residence time in the gut than in adults (Kostial et al., 1979a). In spite of these differences we found that rat’s diet administered to sucklings 1 to 2 weeks before normal weaning decreased metal absorption. The absorption values were still much higher than those usually observed in adult rats. However, under our experimental conditions sucklings consumed only small amounts of rat’s diet over the 8-hr artificial feeding period and also they were returned to their mothers, i.e., to milk, immediately after the end of the radioisotope administration. Therefore the reabsorption during the enteral recycling of the metals was not affected by rat’s diet but by milk. Differences found between the groups are therefore likely to be underestimated under our experimental conditions.
Sr, Cd,
AND
Hg ABSORPTION
IN SUCKLING
RATS
285
There are several possible explanations for the effect of rat’s diet on metal absorption. The higher trace element content is not likely to be one of them, since we recently found that the addition of iO0 ppm Fe, 50 ppm Zn, 200 ppm Mn, and 20 ppm Cu to milk caused almost no changes in the absorption and retention of orally administered cadmium and mercury in sucklings (Kostial et al., 1980). Rat’s diet could accentuate the extrusion of cells from the villi where the metal is deposited in sucklings (Inaba and Lengemann, 1972; Sasser and Jarboe. 19771, but under our experimental conditions it is more likely that it primarily prevented metal deposition in the gut. This specially applies to cadmium and mercury which show a high retention in the “gut compartment” after oral administration in sucklings (Kostial et cl/.. 1979a). Mercury from gut seems to be specially accessible to interaction with the luminal content since a change of diet several days after a single oral administration of *03Hg causes considerable changes in the gut and carcass retention of this metal (Kostial et nl., 1979b). All this indicates that some ligands from the rat’s diet have a higher affinity for metals than the ligands involved in the first step of intestinal absorption, i.e.. in the transfer of metal from the intestinal lumen into the mucosa. It can be concluded that dietary factors participate in the high absorption of metals in neonates and that further studies into the absorption mechanism in sucklings in relation to diet are needed. ACKNOWLEDGMENT This work was partially supported under a research grant from the U.S. Environmental Agency.
Protection
REFERENCES Bremner, 1. (1979). The toxicity of cadmium. zinc, and molybdenum and their effects on copper metabolism. Proc. Nutr. SW. 38, 235-242. Forbes, G. B.. and Reina. J. C. (1972). Effect of age on gastrointestinal absorption (Fe, Sr, Pb) in the rat. J. Nlrrr. 102, 647-652. Fox. M. R. S. (1979). Nutritional influences on metal toxicity: Cadmium as a model toxic element. En\~irc~rl. Hvnlrh Prr.sprct. 29, 95% 104. Inaba, J.. and Lengemann, F. W. (1972). Intestinal uptake and whole body retention of “‘Cc by suckling rats. Hmlrh Phys. 22, 169- 175. Kostial, K., Kello. D., Jugo, S.. Rabar, I., and Maljkovic, T. (1978). Influence of age on metal metabolism and toxicity. Environ. Hralth Prrsprct. 25, 81-86. Kostial. K.. Rabar, I.. Blanusa, M., and Landeka, M. (1979a). Effect of age on heavy metal absorption. Proc.. Nlrtr. SM. 38, 251-256. Kostial. K.. Rabar, I., and Ciganovic, M. (1980). The influence of trace elements on cadmium and mercury absorption in suckling rats. In “Abstracts, International Conference on Industrial and Environmental Xenobiotics: Biotransformation and Kinetics, May 27-30. Prague.” p. 37. Kostial, K.. Rabar, I.. Ciganovid. M., and Simonovic, I. (1979b). Effect of milk on mercury absorption and gut retention in rats. Err//. Environ. Conform. Taxicd. 23. 566-S71. Kostial, K., Simonovic. I., and PiSonic. M. (1967). Effect of calcium and phosphates on gastrointestinal absorption of strontium and calcium in newborn rats. Nrrrrrrr (Lr~rnlon) 215, 1181, 1182. Nordberg, G. F., Fowler, B. A., Friberg, L., Jernelov, A., Nelson. N., Piscator, M.. Sanstead, H. H.. Vestal. J.. and Vouk. V. B. (1978). Factors influencing metabolism and toxicity of metals: A consensus report. En~~iuon. Hen/t11 Persped. 25, 3-41. Sasser. L. B.. and Jarboe, G. E. (1977). Intestinal absorption and retention ofcadmium in neonatal rat. To.ric~cd. Appl. Pharmcrcwl. 41, 423-431. Shiraishi, Y.. and Ichikawa. R. (1972). Absorption and retention of ““Ce and ““Zr-S’Nb in newborn. juvenile. and adult rats. Hurrlril Phs. 22. 373-378.