gastrointestinal absorption of cadmium in mice during gestation and lactation: ii. continuous...

TOXICOLQCY AND APPLIED PHARMACOLOGY 66, 368-375 (1982)

Gastrointestinal Absorption of Cadmium in Mice during Gestation and Lactation

II. Continuous Exposure Studies’**

MARYKA H.BHATTACHARYYA,*~~ BARTLETT D. WHELTON,~-*~ AND DAVID P.PETERSON*

*Division of Biological and Medical Research, Argonne National Laboratory, Argonne, Illinois 60439, and tDepartment of Chemistry, Eastern Washington University. Cheney, Washington 99004

Received June 3, 1982; accepted September 8. I982

Gastrointestinal Absorption of Cadmium in Mice during Gestation and Lactation. II. Con- tinuous Exposure Studies. BHAITACHARYYA, M. H., WHELTON, B. D., AND PETERSON,

D. P. Toxicol. Appl. Pharmacol. 66, 368-375. The effect on cadmium retention of continuous exposure to drinking water containing low levels of cadmium during pregnancy and lactation was studied in mice. Female mice were provided drinking water ad Zibitum containing ‘09CdC12 (0.03 $Zi logCd/ml, 0.11 ppb total cadmium) throughout either gestation, lactation, or a combined period of pregnancy and lactation. Nonpregnant control mice were exposed to the same cadmium solution for similar time periods. Dams in all three experimental groups retained two to three times more cadmium (expressed as percentage of ingested dose) than did nonpregnant controls. The ‘@‘Cd contents of liver, kidney, mammary tissue, and duodenum increased strikingly in all three groups. Increases in kidney and mammary tissue were particularly apparent during lactation, with increases of fivefold for kidney and at least ninefold for mammary tissue, compared to levels in nonpregnant controls. Increases in lwCd retention by the duodenum were fivefold during gestation and three- to fourfold during lactation. The kidneys of dams exposed during lactation retained 53% of the whole body ‘@‘Cd, while kidneys of nonpregnant controls retained only 27%. Results indicate that pregnant and lactating mice absorb and subsequently retain substantially more cadmium from their diets than do nonpregnant mice.

Maternal diet is an important source of essential minerals to the growing fetus during pregnancy and to the neonate during lactation. In the rat, the gastrointestinal tract of

’ This work supported by the Department of Energy under Contract W-31-109-ENG-38.

* The U.S. Government’s right to retain a nonexclu- sive royalty-free license in and to the copyright covering this paper, for governmental purposes, is acknowledged.

3 To whom all correspondence should be addressed. ’ Work performed at Argonne National Laboratory

under a Faculty Research Participant Program administered by the Argonne Division of Educational Pro- grams, and supported by the U.S. Department of Energy, Office of Energy Research, through its University/Na- tional Laboratory Cooperative Program.

the dam increases both in weight and in total surface area during lactation in response to increased demands for nutrients (Campbell and Fell, 1964; Boyne et al., 1966). Absorp- tion of essential minerals such as calcium (Halloran and DeLuca, 1980; Toverud et al., 1976) and iron (Batey and Gallagher, 1977) also increases during gestation and lactation. Recently we have studied the gastrointestinal absorption of a toxic metal, cadmium, during various stages of pregnancy and lactation. We demonstrated that cadmium absorption in lactating mice increases 2- to 3-fold over that in nonlactating mice (Bhattacharyya et al., 1981). Previously, Kostial and Mom&

004 1-008X/82/1 50368-08$02.00/O Copyright Q l@EZ by Academic Prees. Inc. All rigbta of reproduction in any form reserved.

368

Cd ABSORPTION DURING PREGNANCY AND LACTATION 369

lovic (1972) demonstrated that the percentage of po lead chloride absorbed by lactating rats is 3.4-fold higher than that absorbed by nonlactating rats. It appears, therefore, that absorption by the dam of both essential and toxic minerals can be increased during lactation.

In our first study (Bhattacharyya et al., 198 l), mice were exposed to a single dose of ‘09CdC12 by gavage on a given day of gestation or lactation and were killed 72 hr later. In the study reported here, mice were chron- ically exposed to drinking water containing low levels of ‘09CdC12 (0.11 ppb total cadmium). Mice were exposed either throughout pregnancy, throughout lactation, or throughout a combined period of pregnancy and lactation. This study allowed us to analyze effects of changes in gastrointestinal absorption of cadmium on the cumulative retention of cadmium by the dam. Results confirmed the earlier observation (Bhattacharyya et al., 198 1) that retention of po administered cadmium by the dam increases strikingly during lactation and also demonstrated that a similar effect occurs during gestation. The effect during gastation was not observed in the earlier single-exposure study.

METHODS

B6CF,/Anl mice (the F, generation of the C57BL6 X BALB/c cross, Argonne National Laboratory) were maintained on Wayne Lab Blox diet (Wayne Feeds, Continental Grain, Libertyville, Ill.) and tap water (pH 2.3) ad libitum. Drinking water was acidified to pH 2.3 with hydrochloric acid for control of Pseudomonas. Wayne Lab Blox diet contains 1.20% calcium, 0.93% phosphorus, 340 ppm iron, and 0.25 ppm cadmium (Dr. Joel Drews, Wayne Feeds, personal communication). The cadmium concentration in the drinking water was 0.1 ppb, as determined by flameless atomic absorption spectrophotometry (IL 555 CTF Atomizer, IL 951 AA Spectrophotometer, Instrumentation Laboratories, Wil- mington, Mass.). The animal room lighting schedule was 12 hr light (6 AM to 6 PM) followed by 12 hr dark (6 PM

to 6 AM); the relative humidity was 55%; and the room temperature was 22-23°C.

Female mice, 100 days old with a mean weight of 19 g (*2 g), were bred with male mice of the same age and strain, One male was housed with two females starting

at 5 PM on the day of mating. Females were checked for vaginal plugs at 9 AM the next morning. Females show- ing a vaginal plug were separated into three experimental groups with 10 mice per group. Two control groups of nonpregnant female mice of the same age, weight, and strain as the three experimental groups were also used. All mice were housed individually in plastic cages and were provided tap water ad libitum (pH 2.3) containing carrier-free ‘09CdClz (New England Nuclear, Boston, Mass.). The water contained 0.03 PCi “‘Cd/ml (0.01 ppb ‘%d) and 0.11 ppb total cadmium. Day 1 of gestation was the day on which the vaginal plug occurred, Day 19 was the day of delivery, and the following day, Day 20. was the first day of lactation. Experimental groups were designated 17 P, 17 L, and 38 P + L, in- dicating those exposed for 17 days during pregnancy ( 17 P), 17 days during lactation (17 L), or 38 days during a combined pregnancy and lactation period (38 P + L). Experimental group I7 P received ‘@‘Cd-water continuously from Day 1 to Day 18 of pregnancy; group 17 L received iogCd-water from Day 1 to Day 18 of lactation; group 38 P + L was exposed continuously for 38 days from Day 1 of pregnancy to Day 20 of lactation. The two nonpregnant (NP) control groups were exposed continuously to “%?d-water for 17 (17 NP) or 38 days (38 NP), corresponding to the exposure times for the experimental groups. Litters were adjusted to seven pups per dam on Day 2 of lactation. Water consumption was measured throughout the exposure periods to allow cal- culation of the amount of ‘O’Cd consumed.

Following each exposure period, ‘@Cd water was re- placed by normal tap water (pH 2.3). Mice were killed by ip injection of pentobarbita196 hr after cessation of exposure to “‘Cd-water. Pelt, liver, kidney, reproductive tract, mammary tissue, lung, spleen, heart, stomach, intestine (unrinsed, divided into first 5 cm, next 10 cm, and remaining gastrointestinal tract), and remaining carcass (including all remaining soft tissues) were removed, weighed, and analyzed for “‘Cd content. From each litter, two to four whole pups were rinsed first in 1 M HCI, then in distilled water, and analyzed for ‘mCd content. Tissue samples were immersed in 10% formalin to a volume of 10 ml in polypropylene scintillation vials. ‘mCd analysis was accomplished by measuring the 88- keV gamma ray of “‘Cd in a well-type gamma ray spectrometer (Beckman Gamma 310, Beckman Instru- ments, Irvine, Calif.) with a counting efficiency for the 88-keV gamma ray of 74%. An overall counting efficiency for ‘@‘Cd of 2.75% was achieved, taking into account the 3.72% yield of the 88-keV gamma ray. Some small samples were analyzed on a Beckman Gamma 4000 spectrometer that was calibrated to the Beckman Gamma 310. Counting efficiencies were determined with ‘@Cd standards of sizes appropriate to the samples analyzed, along with a ‘09Cd reference source purchased from New England Nuclear (Boston, Mass.). The total amount of ‘@‘Cd retained in the whole body was calculated as the sum of the “-‘%Zd in the individual body

370 BHATTACHARYYA, WHELTON, AND PETERSON

organs plus the remaining carcass and soft tissues. Cad- mium measured in the gastrointestinal tract was not in- cluded in this sum. ‘@%Jd levels in reproductive tract. lung, spleen, and heart were below the limit of detection. The detection limit was 3 cpm above background; background equalled 17.6 f 1.1 cpm (X f SD, n = 31).

Statistical analyses were conducted by Student’s t test

when data from two groups were compared (e.g., 38 P + L vs 38 NP). A one-way analysis ofvariance (ANOVA)

that handled groups of unequal size, followed by a Dun- can’s multiple range test, was employed for intercom- parison of more than two groups (Zar, 1974).

RESULTS

Mice were exposed to drinking water containing low concentrations of ‘09CdC12 (0.03 &i “‘Cd/ml, 0.11 ppb total cadmium). The fraction of ‘09Cd retained in the whole mouse exposed during gestation (group 17 P) was 2.0 times greater than that in nonpregnant mice (group 17 NP; Fig. 1). Mice exposed during lactation (group 17 L) retained 2.6 times more cadmium than did nonlactating

17NP 17P 17L 38NP 38PtL

FIG. 1. Cadmium retention following exposure during pregnancy, lactation, or the combined period. Five groups of female mice were administered drinking water ad libitum containing ‘WCdC12 (0.03 &i “?Zd/ml, 0.11 ppb total cadmium). One nonpregnant control group ( 17 NP) and two experimental groups (I 7 P and 17 L) were exposed for 17 days, from Day 1 to Day 18 of pregnancy ( I7 P) or lactation ( 17 L). A second nonpregnant control group (38 NP) and a third experimental group (38 P + L) were exposed for 38 days, from Day 1 to Day 39 of the combined pregnancy/lactation pcriod.“%d contents of tissues were determined 96 hr after cessation of exposure. Entire bar represents cadmium retention in the whole mouse. Cadmium retentions in individual tissues are in- dicated as follows: K, kidney; L, liver; M, mammary tissue; R, remaining mouse.

controls (group 17 NP). Mice exposed continuously for 38 days throughout gestation and lactation (group 38 P + L) retained 2.7 times more lo9Cd than did nonpregnant control mice (group 38 NP) exposed for a similar 38-day time period (Fig. 1).

In addition, during the period of lactation only, a striking shift occurred in the fraction of whole body ‘09Cd deposited in various organs. Fifty-three percent of the ‘09Cd in the whole mouse was deposited in the kidneys of lactating mice (group 17 L), whereas only 27 to 33% was deposited in the kidneys of nonpregnant controls (groups 17 NP and 38 NP; Fig. 1 and Table 1). The fraction of whole body ‘09Cd in mammary tissue also increased significantly during lactation, from 2% in nonpregnant controls to 6% in lactating mice (Fig. 1 and Table 1).

Table 1 presents data on water consumption and ‘09Cd contents of individual tissues. Mice consumed about the same amount of water during pregnancy as did nonpregnant controls; during lactation, water consumption increased 35fold. ‘09Cd contents of tissues in Table 1 and Fig. 1 are expressed as percentages of lo9Cd consumed. This expres- sion normalizes for differences in lo9Cd contents due only to differences in water and therefore lo9Cd consumption.

The ‘09Cd contents of the liver, kidney, mammary tissue, and duodenum all increased strikingly in mice exposed during periods of pregnancy and lactation and for the combined test period (Table 1). Increases in kidney and mammary tissue were particularly apparent during the period of lactation (group 17 L), with increases of fivefold for kidney and at least ninefold for mammary tissue compared to levels in nonlactating controls. Increases in lo9Cd retention by the duodenum during pregnancy were fivefold and during lactation were three- to fourfold. lo9Cd in the reproductive tract was below the limit of detection for all groups except Group 38 P + L, the reproductive tract from Group 38 P + L contained only 1 X 10e3% of the ingested dose. “‘Cd deposition in the repro-


TABLE 1

WATERCONSUMFTIONAND '09GlC~~~~~~~~M~~~~T~~~~~~ AFTERADMINISTRATION OFCADMIUM IN DRINKING WATER DURING PREGNANCY, LACTATION, OR THE COMBINED PERIOD'

17 NP (control)

n=9 17 P

n=9

38 NP 17 L (control) 38P+L

n = 10 n= 10 n=8

Water consumption (ml)

ml/mouse/period: ml/mouse/day:

72 + 4 86 + 8 258 + 28 162 + 10 374 f 32 4.2 f 0.2 5.1 f 0.5 15.2 + 1.6 4.3 + 0.3 9.8 f 0.8 (P + L)

4.4 + 0.5 (P only) 14.7 f 1.2 (L only)

‘OsCd content (% ingested dose- X 103)*

Whole mouse (minus GI tract) 110 + 9’ 217 f 33’ 281 +48” 107 f 11 289 f 60*

Liver 37 zk 4’ 96 k 17” 75 + 126 35 f 5 88 + 17* (34) (44 (27) (33) (30)

Kidney 30 + 5’ 85 of: 16’ 150 f 33” 35 + 6 150 + 35* (27) (39) (53) (33) (52)

Mammary tissue <1.93 3.3 + 1.0 16.4 + 1.8* 1.5 f 0.7 13.6 k 3.5* (2) (6) (2) (5)

Remaining carcass 44 k 7” 33 + 56 40 + 5” 35 * 4 38 + 6 (40) (15) (14) (33) (13)

Stomach 4.6 k 1.7b 7.5 + 3.7” 3.7 t 0.56 4.4 i 5.3 3.7 + 0.5 Duodenum 17 * 2’ 80 + 23” 60 f 17” 17 f 2 61 f 11* Jejunum 4.6 + l.Ob 9.4 + 3.3” 9.2 f 3.2’ 3.6 + 1.0 8.6 k 2.7* Remaining GI

tract 48 f 27’ 34 f 13” 34 f 11° 15 f 9 20 f 5 Litter of seven

PUPS4 - <65 30 fl7 - 72 +19

’ Groups of mice and their exposure to ‘09Cd are described in Fig. I. Values presented are X f SD. Numbers in parentheses are percentages of whole body cadmium (minus GI tract) present in the organ.

’ Means for groups 17 NP, 17 P, and 17 L were tested by ANOVA followed by Duncan’s multiple range test. Means in a given row with the same letter superscripts are not significantly different (p < 0.05). Student’s t test was used to compare mammary tissue means for 17 P vs 17 L (since levels for 17 NP were below the detection limit), and to compare all tissue means for 38 NP vs 38 P + L; significance levels: * p < 0.001.

3 Mammary tissue samples for group 17 NP contained less than 3 cpm above background, i.e., less than the detection limit for the counting conditions employed. As listed, <3 cpm is equivalent to <I .9 X lo-‘% of the dose ingested by group 17 NP.

4 ‘09Cd content of litters was calculated from the two ( 17 L and 38 P + L) or four ( 17 P) pups per litter that were analyzed.

5 Samples analyzed from Group 17 P contained two pups per vial; all vials contained 13 cpm above background. Seven pups (one litter) therefore contained < 11 cpm, which is <6 X 10e3% of the ingested dose, as listed.

ductive tract was thus low and did not in- below the limit of detection (Table 1). The crease during gestation as did the mammary litters of pups from the other two experi- tissue during lactation. mental groups contained 11% ( 17 L) and 25%

ro9Cd contents of pups analyzed from (38 P + L) of the lWCd present in the whole dams exposed during gestation (17 P) were bodies (minus GI tract) of the dams (Table

372 BHATTACHARYYA, WHELTON. AND PETERSON

1; compare lo9Cd in pups with that in dams). lo9Cd in pups may represent lo9Cd transferred from the dams via milk. Since exposure to lo9Cd water continued until Days 18 and 20 of lactation for the 17 L and 38 P + L groups, respectively, it is also possible that the pups drank small amounts of their mothers’ water to achieve their body bur- dens.

Since changes in organ weight occur during gestation and lactation, it is important to consider the cadmium concentration (% ingested dose/g) in selected organs in addition to the total amount of ‘09Cd in the organ. As can be seen from Table 2, kidney and duodenum had the highest lo9Cd concentrations of all organs in both experimental and control groups. Although the liver increased in amount of lo9Cd retained during pregnancy and lactation (Table I), corresponding increases in liver mass occurred, such that no large change in lo9Cd concentration in liver was observed for mice exposed during pregnancy and/or lactation (Table 2). In contrast, the kidney and duodenum increased both in organ mass and ‘09Cd concentration (Table 2). Increases in the kidney were somewhat

greater for mice exposed during lactation (3.4-fold) than during gestation (2.3-fold). The reverse was true for the duodenum; the increase in lo9Cd concentration in the duodenum was greater in mice killed at the end of gestation (3. l-fold) than at the end of lactation (2.3-fold). Although the cadmium concentration increased in the duodenum, no change in concentration occurred in the adjacent jejunum (Table 2).

Data so far presented are expressed in percentages of ingested lo9Cd in tissues. In Table 3, tissue levels are expressed in picograms ‘09Cd per organ, to evaluate the combined effects of increased gastrointestinal absorption and retention, as well as increased ‘09Cd intake accompanying increases in water consumption. As can be seen, increases in pi- cogram amounts of ‘09Cd (6- to 20-fold) were much greater than increases in percentages of ingested dose (2- to 9-fold).

DISCUSSION

Pregnant mice exposed continuously during gestation to drinking water containing ‘09CdC12 retained 0.22% of the ingested ‘@‘Cd

TABLE 2

lo9Cd CONCENTRATION IN MOUSE TISSUES AFTER ADMINISTRATION OF CADMIUM IN DRINKING WATER

DURING PREGNANCY. LACTATION. OR THE COMBINED PERIOD’

‘09Cd concentration (% ingested dose/g X 10’)

17 NP 38 NP (control) 17 P 17 L (control) 38P+L

Liver 35 i 4b 44 + 70 32 + 5’ 33 f 5 38 i 7 Kidney 114 f 20’ 265 _t 466 392 f 79” 128 * 18 415 +93* Mammary tissue <3.2* 1.5 * 0.4 8.3 t- 1.4* 1.3 k 0.6 7.2 + 1.7* Stomach 19+ 8” 9 + 56 11 f 2b 15 +16 9 +2 Duodenum 107 f 18’ 334 + 75” 246 + 59’ 90 fl7 265 f 84* Jejunum 16+ 4” 19 + 6” 19 + 8” 11 k 2 18 f 6t

’ %d concentrations were calculated for the same five groups of mice described in the text and Fig. I. Values presented are X k SD. Means for groups 17 NP, 17 P, and 17 L were tested by ANOVA followed by Duncan’s multiple range test. Means in a given row with the same letter superscripts are not significantly different (p i 0.05). Student’s 1 test was used to compare mammary tissue means for 17 P vs 17 L, and to compare all tissue means for 38 NP vs 38 P + L; significance levels: t p < 0.05; * p < 0.00 1.

* Mammary tissue samples for group 17 NP contained less than 3 cpm above background, i.e., less than the detection limit for the counting conditions employed. As listed, ~3 cpm per mammary tissue sample is equivalent to (3.2 X IO-% ingested dose/g.

Cd ABSORPTION DURING PREGNANCY AND LACTATION

TABLE 3

373

EFFECTS OF PREGNANCY AND LACTATION ON lo9Cd CONTENT OF MOUSE ORGAN?

Sample

“‘Cd content (pg)

38 NP (control) 38P+L

Increase in ‘@Cd

(pg)

Increase in % ingested

dose*

Kidney 0.72 + 0.15 Liver 0.71 + 0.13 Mammary gland 0.03 + 0.02 Whole body 2.2 k 0.2

6.8 + 1.6* 4.0 + 0.8* 0.61 + 0.16*

13.4 _t 1.8*

9.4-fold 5.6-fold

20.3~fold 6. l-fold

4.3-fold 2.5-fold 9. l-fold 2.7-fold

’ Pregnant mice were provided water containing ‘09CdC12 throughout gestation and lactation (38 days) as described in the text and Fig. 1. Nonpregnant control mice were similarly exposed for 38 days. Values given are X + SD. 38 NP = nonpregnant control mice. 38 P + L = mice exposed throughout pregnancy and lactation. * indicates values that are significantly greater than 38 NP values (p < O.OOl), according to Student’s t test.

* Increases are calculated from data in Table 1 to compare groups 38 P + L and 38 NP.

in their whole bodies (minus GI) when killed on Day 2 of lactation (Table 1). Age-matched, nonpregnant controls retained 0.11%. The twofold increase in retention of cadmium by the dam during gestation was not entirely expected, since no significant increase in the gastrointestinal absorption of cadmium by the dam was observed on Day 8 or 15 of gestation in our earlier study (Bhattacharyya et al., 198 1). Data of Pietrzak-Flis et al. (1978) however, support the findings reported here. In their study, rats were exposed to various concentrations of cadmium in drinking water (0.1 to 5 ppm) from the day of weaning to about 120 days of life. The kidneys of adult rats who had experienced gestation just prior to being killed contained approximately two times as much cadmium as did similarly exposed nonpregnant adults. Fetal growth is rapid during the last few days of gestation in the mouse and rat, and during that time increases in intestinal transport of calcium (Halloran and DeLuca, 1980) and iron (Batey and Gallagher, 1977) occur in the maternal animal. It is possible, therefore, that an increase in the gastrointestinal absorption of cadmium may also occur just prior to delivery, as it does for calcium and iron, ac- counting for the increased retention of cadmium observed in mice and rats at the end of gestation.

In the present continuous exposure study, cadmium retention in the mouse was measured, and not its gastrointestinal absorption (which equals the sum of cadmium retention and cadmium excretion). The values for gastrointestinal absorption and retention must have been very similar in our study, however, since cadmium excretion is low at the doses employed [less than 2% of the absorbed cadmium would have been excreted from the mouse via urine (Bhattacharyya et al, 198 1) and feces (Cherian et al., 1977; Lucis et al., 1969) at the doses employed]. The twofold increase in cadmium retention observed during gestation could not have been achieved by simple blockage of cadmium excretion pathways, leaving absorption levels un- changed, a twofold increase in the gastrointestinal absorption of cadmium must also have occurred.

Following exposure to cadmium during lactation, the increase in ‘@Cd retained by the dam was 2.6-fold. This increase in retention is similar to that observed during mid- lactation in our previous short-term exposure study. Pietrzak-Flis et al. (1978) found that, for rats exposed to 1.1 ppm cadmium during gestation and lactation, the concentration of cadmium in the kidney increased from 23 pg/ 100 g on Day 1 of lactation to 48 pg/ 100 g on Day 21 of lactation, an increase of 25

374 BHATTACHARYYA, WHELTON, AND PETERSON

pg/lOO g (Fig. 1, Group 3, in Pietrzak-Flis et al., 1978). In nonpregnant rats, an increase of about 3 pg/ 100 g is extrapolated from the graph from 100 to 130 days of life (Fig. 2, Group 3, in Pietrzak-Flis et al., 1978), an exposure period corresponding to that of lactation in the lactating rats. This increase in cadmium deposition in the kidney following exposure during pregnancy and lactation is 8-fold (25 pg/lOO g + 3 Kg/ 100) and is similar to the 9-fold increase observed in our present study (Table 3). At concentrations higher than the one used in this study, therefore, similar observations have been made of enhanced uptake and tissue deposition of cadmium in the maternal animal during lactation.

During gestation, most of the lo9Cd absorbed by the dam through the intestine was retained in maternal organs; less than 0.006% of the ingested ‘09Cd, or less than 3% of the internally retained dose, was passed on to the pups (Table 1). Other investigators have demonstrated in rats a similar low level of transfer of cadmium to the fetus during gestation, along with a striking buildup of cadmium in the placenta (Pietrzak-Flis et al., 1978; Ragan and Sweeney, 1978). In contrast, however, Kelman and Walter (1977) have shown that cadmium moves readily across the placenta in the isolated perfused placenta of the guinea pig. In addition, Hub- ermont et al. (1978) have demonstrated that the median cadmium concentration in the blood of human newborns, taken from the umbilical cord, is at least one-third of the cadmium concentration in maternal blood taken at delivery. The low level of transfer of cadmium to the fetus during gestation may therefore be due to rapid sequestration of cadmium by maternal tissues, including the placenta, with resulting low concentrations of cadmium in blood, rather than to a lack of placental permeability to cadmium.

During lactation, more cadmium appeared to be transferred to pups than during gestation. Less than 3% of maternal lc@Cd was transferred to pups during gestation

(group 17 P), while 11% appeared in the pups after exposure during lactation (group 17 L), and 25% appeared after exposure during the combined period (group 38 P + L: Table 1). Transfer to pups was greater for dams exposed for the combined period, suggesting that exposure of the dam during gestation may have enhanced transfer of cadmium via milk during lactation. The possibility cannot be excluded that ‘09Cd in the pups represents ‘09Cd obtained by sampling the mother’s water supply. This possibility appears un- likely, however, since only 10 and 40 ~1 of “?Zd-water would need to have been consumed per pup in the 17 L and 38 P + L groups, respectively, to account for the lo9Cd in the litters. These volumes are probably smaller than volumes a 5-g mouse (mouse weight at the end of lactation) would drink were it to sample its mother’s water supply.

In general, changes in cadmium concentration in various tissues following continuous exposure during pregnancy and/or lactation reflected changes observed in the previous short-term exposure study (Bhat- tacharyya et al., 198 1): lc@Cd concentrations in kidney, duodenum, and mammary tissue increased, while liver and jejunum doubled both in weight and in lwCd content, with no striking change in cadmium concentration. In contrast, however, no increase in cadmium absorption occurred on Day 8 or 15 of gestation in the short-term study, while pregnant mice exposed throughout gestation in the present study retained two times more io9Cd than did nonpregnant controls. These data suggest that cadmium absorption increases after Day 15 of gestation.

The increase in retention of cadmium by the dam during lactation was accompanied by changes in the tissue distribution of cadmium, such that 53% instead of 26 to 33% of the deposited cadmium was retained by the kidney during lactation. Considering the three factors, increased gastrointestinal absorption, increased kidney deposition, and increased water consumption, the overall effect was that the amount of io9Cd (pg) de-


posited in the kidneys of mice exposed during both pregnancy and lactation was 9.4 times greater than in nonpregnant control mice (Table 3). The possibility that increased ac- cumulation of cadmium in the kidney during gestation and lactation could result in generation of a toxic response to cadmium at a lower level of exposure in multiparous than in nonpregnant animals needs to be tested by further investigation.

ACKNOWLEDGMENTS

We thank E. S. Moretti for her excellent technical assistance and C. A. Fox for her help with statistical analyses.

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gastrointestinal absorption of cadmium in mice during gestation and lactation: ii. continuous...

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