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Oct 2, 1993 - The Efficacy of Mineral Oil Combined with Feed Restriction in Enhancing the. Elimination of Heptachlor Epoxide from Mink (Mustela vison).
Arch. Environ. Contam. Toxicol. 26, 374-380 (1994)

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Environmental Contamination a n d Toxicology © 1994 Springer-VerlagNew York Inc.

The Efficacy of Mineral Oil Combined with Feed Restriction in Enhancing the Elimination of Heptachlor Epoxide from Mink (Mustela vison) J. A. Crum ~, R. J. Aulerich ~, D. Polin 1, W. E. Braselton 2, S. J. Bursian ~ Department of Animal Science and the Institute for Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824, USA

Department of Pharmacologyand Toxicologyand the Institute for Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824, USA Received: 7 August 1993/Revised:2 October 1993 Abstract. Adult female mink previously fed diets containing 0 (control) and 6.25 mg heptachlor/kg diet for 181 days were fed either the same control diet ad libitum (AL) or the control diet containing 10% mineral oil and restricted by 45% of ad libitum intake (MO/R) for 21 days to determine the efficacy of the latter treatment in enhancing the elimination of heptachlor epoxide (HE) from mink. Kit mink (2-3 months of age) whelped by dams of the control and 6.25 mg/kg groups were also fed the MO/R or AL diets for 21 days. Daily consumption (g/kg bw/ day) of the A L diet by kit mink was significantly greater than consumption of the same diet by the adult females. Body weights of the control adults and the control and 6.25 mg/kg kits were significantly reduced by feeding the MO/R diet. Two adults from the control group and one adult from the 6.25 mg/kg group fed the MO/R diet died during the 21-day period. No mortalities occurred in kit mink fed either diet. Administration of the MO/R diet caused a significant reduction in body fat of the control adults and kits, but not in the 6.25 mg/kg adults and kits. Decreases in body fat of the MO/R groups were not associated with greater elimination of HE when compared to the AL groups. Comparison of HE body burdens in adult female and kit mink from the former 6.25 mg/kg heptachlor group at day 21 indicated that consumption of the MO/R diet did not increase the elimination of HE when compared to day 21 HE body burdens in adults and kits fed the AL diet. Heptachlor epoxide body burdens were reduced by 78 (MO/R) and 80% (AL) in the 6.25 mg/kg adults, while HE elimination from the 6.25 mg/kg kits was 96 and 93%, respectively. The half-lives of HE in the adults were 9.1 (AL) and 10.9 (MO/R) days, and 4.9 (AL) and 4.6 (MO/R) days in the kits. These results indicate that HE is readily mobilized and eliminated from mink.

The extensive and widespread past use of the insecticide heptachlor (1,4,5,6,7,8,8-heptachlor-3a,4,7,7a-tetrahydro-4,7-

Correspondence to: S. Bursian

methanoindene), together with its recalcitrant properties, have inadvertently resulted in exposure of non-target organisms. The most common and economically significant exposures have occurred in the livestock industry as a result of heptachlor's use on agricultural crops. Despite restrictions placed on the use of heptachlor by the United States Environmental Protection Agency (USEPA 1978), secondary contamination of human food products has occurred in Missouri, Oklahoma (Raisbeck et al. 1986; Stehr-Green et al. 1986), Hawaii (Smith et al. 1984; Le Marchand et al. 1986), and more recently in Arkansas (Flora 1989). From a human health and economic perspective, the most significant of these contamination incidences occurred in 1982 on the island of Oahu, Hawaii where milk was found to contain violative concentrations of heptachlor (Le Marchand et al. 1986). Over eight million pounds of milk were contaminated as a result of dairy cattle consuming feed supplemented with heptachlor-treated pineapple plant foliage (Smith et al. 1984). Of greater importance was concern that adverse health effects could develop in the Oahu population, since testing of stored milk samples indicated that milk containing heptachlor residues in excess of the current EPA action level of 0.1 mg/kg (fat basis) had been sold on the island for a 27- to 29-month period before the first recall (Le Marchand et al. 1986; Smith et al. 1984). Because heptachlor epoxide (HE), the primary metabolite of heptachlor, is a lipophilic molecule that accumulates in adipose tissue (Radomski and Davidow 1953), methods to remove HE from tissue stores are of considerable interest to the livestock industry and are ultimately important for the protection of humans from potential long-term health effects. A review of various HE decontamination strategies indicates that the efficacy of the method is dependent on the animal species tested. In addition, the majority of techniques have focused on enhancing intestinal elimination, since most residual chlorinated hydrocarbons are excreted primarily in the feces (Rozman 1985). Metabolic inducers of biotransformational enzymes in the liver enhanced the clearance of 14C-heptachlor from rats (Rozman 1984), but were not effective in increasing the elimination of 14C-heptachlor from sheep (Smith et al. 1989) or in

Eliminationof Heptachlor Epoxide from Mink

reducing HE body burdens in cattle (Raisbeck et al. 1989). Intestinal adsorbents (lipotropic binding agents), such as mineral oil, liquid paraffin and hexadecane, were highly effective in enhancing fecal elimination of several polyhalogenated hydrocarbons from rats, rhesus monkeys and goats (Richter et al. 1977; Rozman et al. 1981a, 1981b; Rozman et al. 1982a, 1982b; Polin et al. 1987), but failed to increase elimination of heptachlor residues from rats, sheep, pigs, and cattle (Rozman 1984; Smith et al. 1989; Raisbeck et al. 1989). Techniques to mobilize and reduce body fat stores, such as restricting dietary intake, would seem the most reasonable approach to decrease contaminant body burdens as adipose tissue is the principal reservoir of most lipophilic toxicants. However, this method was not effective in reducing body burdens of HE-contaminated cattle (Raisbeck et al. 1989), and experiments with rats demonstrated that redistribution of the contaminant to other lipid storage sites can occur (Wyss et al. 1982). Various combinations of the above methods have consistently resulted in successful elimination of many xenobiotics from several animal species. Cook and Wilson (1971) demonstrated that a combination of activated carbon and phenobarbital was more effective than either separately in removing dieldrin from cattle. Mutter et al. (1988) reported increases in fecal excretion of DDE from gerbils when feed restriction was combined with administration of sucrose polyester, a lipophilic binding agent. Feeding reduced quantities of diets containing mineral oil was also successful in hastening the elimination of PCBs, PBBs, hexachlorobenzene and pentachlorophenol from chickens (Polin et al. 1985, 1986a, 1986b). Subsequent experiments using this method in rats exposed to PBBs indicated that the greatest reductions in body burdens occurred in rats fed diets containing 10% mineral oil and restricted by 45% of ad libitum consumption (Polin et al. 1991). The purpose of the present study was to determine if a diet containing 10% mineral oil and restricted by 45% of ad libitum intake would enhance the elimination of HE from adult female and kit (young) mink previously exposed to heptachlor in a 181 day feeding trial (Crum et al. 1993).

Materials a n d M e t h o d s

Adult female standard dark mink (Mustela vison) from stock raised at the Michigan State University Experimental Fur Farm that were fed 0 (control) and 6.25 mg technical-grade heptachlorl/kg diet for 181 days (Crum et al. 1993) were randomly divided into two dietary groups. Mink in one group were fed a control diet2 ad libitum (AL), identical to the diet provided during the previous 181-dayperiod. Mink in the other group were provided the control diet supplemented with 10% mineral oil and fed in quantities 45% less than ad libitum intake of the AL group. This diet is referred to as the MO/R diet. Young mink (kits ranging from two to three months of age) whelped by dams fed the control diet or the 6.25 mg/kg heptachlor diet in the previous trial were

Velsicol Chemical Corp., Memphis, TN; Technical grade heptachlor; purity 72%, Lot No. 53714421. 2 The control diet consisted of 25% mink cereal, 20% chicken byproducts, 20% ocean fish trimmings, 5% liver, and 30% water. As fed, the diet contained 13.9% protein, 6.8% fat, 4.1% ash, and 62.6% moisture (National Environmental Testing Inc, Chicago, IL).

375 Table 1. Study design for the 21-day elimination period

Dietary treatment ALb

MO/Rc

Prior dietary heptachlor (mg/kg diet)a

No. adults

No. kits

No. adults

No. kits

0 (control) 6.25

4 4

9 9

4 4

9 9

a

Dietary treatments fed to mink during a 181-day feeding trial (Cram

et al. 1993)

bControl diet fed ad libitum cControl diet containing 10% mineral oil fed at 45% of ad libitum consumption also randomly and equally divided into the two groups described above (Table 1). Animals were maintained on the two diets for 21 days (elimination period) beginning on July 2 and ending on July 22, 1989. To assure that animals fed the MO/R diet were truly receiving 45% less feed than mink fed the AL diet, a 3-day moving average of feed consumed per day by adult female and kit mink fed the AL diet was calculated. Therefore, adjustments to the MO/R diet were made every fourth day with a separate corresponding average calculated for adult female and kit mink. Mink were housed individually in wire cages (76 cm long × 61 cm wide × 46 cm high) suspended above the floor in an animal room. Animals were observed daily for any adverse response to the treatments. Water was provided ad libitum throughout the 21-day period to all mink. Temperature within the animal room approximated ambient temperature, which averaged 22°C during the study period (NOAA 1989). Ventilation was provided by an exhaust fan and ceiling vents. Photoperiod was regulated to simulate natural light conditions. Prior to the beginning of the present study, four control and three 6.25 mg/kg adult mink from the previous investigation were euthanized (CO2) to determine whole-body HE concentrations. Similarly, eight and nine kits from the control and 6.25 mg/kg groups, respectively, of the previous study were euthanized for HE analysis. At the completion of the study, all mink were euthanized (CO2) to determine whole-body HE concentrations. Methods for preparation and analysis of mink carcasses were previously described (Crum et al. 1993). Statistical analyses to determine the effects of the elimination treatment on feed consumption, body weight, body fat content, total HE body burdens, and whole-body HE concentrations in adult female and kit mink from the prior heptachlor treatment groups were conducted, using the computer software program Toxstat (Gulley et al. 1989). The Student t-test was used to evaluate feed consumption and body weight differences within and among prior heptachlor treatment groups for adult females and kits separately, while feed consumption differences between adults and kits fed the AL diet were compared by Tukey's method of multiple comparisons of means. Tukey's method was also used to examine differences in body fat content, total HE body burden and whole-body HE concentration within prior heptachlor treatment groups for adult female and kit mink separately, except where data were found to be heterogeneous. If the data were determined to be heterogeneous, via Bartlett's test, they were then transformed by taking the square root of the values. If the transformed data passed Bartlett's test for homogeneous variance, they were evaluated by Tukey's method. If the transformed data failed this test, the KruskalWallis nonparametric test was performed to compare group means. Statements of significance are based on p < 0.05.

Results

Feed consumption by adult female mink fed the AL diet is presented in Figure 1. The quantity of feed consumed per day

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by female mink from the former control group varied considerably during the elimination period compared to females formerly fed the 6.25 mg/kg heptachlor diet. Mean daily feed intake by mink from the control (131 g/mink/day) and 6.25 mg/kg (141 g/mink/day) groups was not significantly different over the elimination period. However, when expressed on a body weight (bw) basis, feed consumption by the 6.25 mg/kg females was significantly greater than that of the control females (157 versus 110 g/kg bw/day, respectively). Feed consumption by kit mink (approximately 3-4 months of age) from both the control and 6.25 mg/kg groups fed the AL diet was markedly similar over the elimination period (Figure 2). The average amount of feed consumed by each group varied daily, with the greatest fluctuations occurring during the first 10 days. Daily feed intake by the control (175 g/kit/day) and 6.25 mg/kg (169 g/kit/day) kits was significantly greater than intake by adult female mink in the same groups. Based on the mean body weight of these two groups at the end of the elimination period, feed consumption was estimated at 171 and 185 g/kg bw/day for the control and 6.25 mg/kg kits, respectively. However, these values are likely underestimates as kits were rapidly growing and gaining weight during this period. Feed consumption by adult female mink on the MO/R diet ranged from 65 to 100 g/mink/day, while kits on this diet consumed 85 to 105 g/kit/day. These quantities equaled the allotted amount of feed supplied to each mink, and was based on mean daily consumption rates of mink fed the A L diet. Both adults and kits consumed the allotted quantity of food each day, with the exception of a small number of adult female mink that either rejected feed or consumed only a small portion of the diet the first two days. Body weights of the control and 6.25 mg/kg adult female mink fed the AL or MO/R diet were not significantly different on day 0 of the elimination period (Table 2). However, the surviving adult females from the control group fed the MO/R diet weighed significantly less than control females fed the AL

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Fig. 1. Consumption of the ad libitum (AL) diet during the 21-day elimination period by adult female mink previously fed control diet (--) and 6.25 mg heptachlor/kg diet (- -) for 181 days

diet at the end of the elimination period. Although the percent body weight loss of surviving female mink from the 6.25 mg/kg group fed the MO/R diet (22%) was similar to control females on the same diet (25%), there was no significant difference in body weights between 6.25 mg/kg females fed the AL or MO/R diets at day 21 of elimination. This was likely due to the lower initial body weight of the AL animals at day 0 compared to the weight of the MO/R animals in this group. The body weights of kit mink were not recorded at day 0 of elimination. However, the body weights of their litter mates from the former control and 6.25 mg/kg groups that were euthanized for HE body burden analysis to compare with this study were not significantly different. This suggests that the body weights of the control and 6.25 mg/kg kits at day 0 of elimination were similar. At day 21, the body weights of the control and 6.25 mg/kg kit mink fed the MO/R diet were significantly below the body weights of kits from the same groups fed the A L diet (Table 2). Mortality during the 21-day period occurred only among the adult female mink fed the MO/R diet. Two adult female mink from the control group fed the MO/R diet died on days 18 and 21 of the trial. The female that died on day 18 consumed only a minute amount of feed up to its death, but had a body fat content of 35.1%. The other female consumed the daily allotted amount of the MO/R diet up to its death, but bad a body fat content of only 1.5%. In comparison, the mean body fat percentage of the control females on the A L diet was 28.2% (Table 3). One adult female from the 6.25 mg/kg group also fed the MO/R diet died on the 8th day of the trial. This mink consumed the daily allotted amount of the MO/R diet up to its death, and had a low body fat content of 1.2%. Analysis of the control adult females dying on days 18 and 2 ! revealed total HE body burdens of 6.3 and 1.5 ~zg/animal, respectively. These values corresponded to whole-body HE concentrations of 0.008 and 0.004 ~g/g bw, respectively. The adult female mink from the 6.25 mg/kg group that died had a

Eliminationof Heptachlor Epoxide from Mink

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Fig. 2. Consumption of the ad libirum (AL) diet during the elimination period by kit mink ( 3 4 months of age) previously weaned by dams fed control diet (--) and 6.25 rag heptachlor/kg diet (- -) heptachlor

Table 2. Body weights of adult female and kit mink at the beginning (day 0) and end (day 21) of the elimination period Body weight (g)a Prior dietary heptachlor (mg/kg diet)b

Dietary treatment

Adults

0 (control)

AL d

MO/Re 6.25

AL

MO/R

Kits

Day 0c

Day 21

Day 0

Day 21

1177 --- 127 (4) 945 --- 127 (4) 868 --- 65 (4) 900 --- 102 (4)

1201 ± 110 (4) 658 --- 44(2)f 932 ± 82 (4) 767 ± 68 (3)

ND ND ND ND

1024 - 79 (9) 605 --- 20(9)f 915 ± 54 (9) 577 ± 26(9)f

aData expressed as mean + standard error. Sample size in parentheses. ND = not determined bDietary concentrations of heptachlor fed to adult female mink for 181 days. Kits consumed these diets from five to nine weeks, in addition to in utero and lactational exposure (Crum et al. 1993) cBody weights of adult female mink after l 81 days on specified heptachlor treatment (Crum et al. 1993) dControl diet fed ad libitum eControl diet containing 10% mineral oil fed at 45% of ad libitum consumption fSignificantly different from corresponding ad libitum group at p < 0.05

total HE body burden of 1,548.8 Izg, which was equivalent to a whole-body HE concentration of 3.3 p,g/g bw. There were no mortalities of kit mink during the elimination period. Heptachlor epoxide body burdens and whole-body concentrations of HE in adult female mink at the beginning and end of the elimination period are presented in Table 3. As expected, HE body burdens in the control adult females were very low prior to the beginning of the elimination period. Nonetheless, body burdens decreased 41 and 66% in the control females fed the A L and MO/R diets, respectively, over the 21-day period. Day 21 body burdens and whole-body concentrations of HE in the control adult females fed either diet were not significantly reduced when compared to values for these parameters at day 0. Heptochlor epoxide body burdens and whole-body HE concentrations at day 21 were significantly reduced below day 0 values in the 6.25 mg/kg adult female mink fed the A L and MO/R diets (Table 3). Body burdens decreased 80 and 78% for mink fed the AL and MO/R diet, respectively. The half-lives of HE, based

on HE body burdens or whole-body HE concentrations, were approximately 10 days for both the A L and MO/R females. The percent body fat of control adult female mink fed the MO/R diet was significantly reduced at the end of elimination, whereas control females fed the AL diet had a nonsignificant increase in body fat content relative to percentages in females at day 0 (Table 3). Neither diet consumed during the 21-day period had a significant effect on body fat content in the 6.25 mg/kg females, although mink fed the MO/R diet had reduced percentages, with values comparable to those reported for control mink fed the same diet. Similar to adult female mink from the prior control group, kits whelped by dams in this group contained only trace amounts of HE prior to the beginning of the trial (Table 4). Consumption of either diet for 21 days resulted in no significant change in whole-body HE concentrations and HE body burdens compared to values at day 0 of elimination. Nevertheless, body burdens decreased 75 and 70% in the control kits fed theAL and

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Table 3, Body burdens and whole-body concentrations of heptachlor epoxide (HE) and percent fat in adult female mink at the beginning (day 0) and end (day 21) of the elimination period Prior dietary heptachlor (mg/kg diet) a 0 (control)

6.25

Day of elimination

Dietary treatment

Sample size

HE body burden (Ixg/mink) b'°

Whole-body HE concentration (Ixg/g bw) b'~

Day 0 Day 21

-ALd

4 4

MO/R e

2

-AL

3 4

MO/R

3

5.8 -+ 1.4 a 3.4 -+ 2.2 a (4l) 2.0 -+ 0.1 a (66) 8416.6 -+ 839.3 a 1697.3 --+ 257.0 b (8O) 1845.6 --- 553.2 b (78)

0.005 --- 0.001" 0.003 + 0.002 a (40) 0.003 + 0 a (40) 8.872 --+ 0.727 ~ 1.791 --- 0.131 b (80) 2.323 -+ 0.494 b (74)

Day 0 Day 21

Body fat (%)b,c 22.9 -+ 1.7 a 28.2 --- 2.8 ~ 7.9 + 1.8 b 18.0 + 0.6 a 19.0 -+ 2.9 ~ 11.4 + 3.1 a

aDietary concentrations of heptachlor fed to adult female mink for 181 days (Crum et al. 1993) bData presented as mean --+ standard error. Number in parentheses is percent reduction from value at day 0 CMeans within same column for each prior dietary treatment with different superscripts are significantly different (p < 0.05) d Control diet fed ad libitum eControl diet containing 10% mineral oil fed at 45% of ad libitum consumption

Table 4. Body burdens and whole-body concentrations of heptachlor epoxide (HE) and percent fat in three to four month-old mink kits at the beginning (day 0) and end (day 21) of the elimination period Prior dietary heptachlor (mg/kg diet) a 0 (control)

Day of elimination

Dietary treatment

HE body burden (t~g/mink) b'c

Whole-body HE concentration (~g/g bw) b'c

Day 0 Day 21

-ALd

6.1 -+ 0.8 a 1.5 -+ 1.5 a (75) 1.8 --- 0.3 a (7O) 4338.6 + 504.0 a 314.0 -+ 48.7 t' (93) 162.8 + 5.6 b (96)

0.002 _+ 0.001 a 0.001 --_ 0.001 a (50) 0.003 --_ 0 a (+50) 6.616 -+ 0.032 a 0.348 + 0.059 b (95) 0.282 + 0.006 t' (96)

MO/Re 6.25

Day 0 Day 21

-AL MO/R

Body fat (%)b,c 12.3 4- 0.7 a 20.8 -+ 1.2 b 7.2 --- 1.2 c 11.8 - 0.7 a 22.4 --- 1.1 b 8.1 --- 2.1 a

aKits consumed these diets from five to nine weeks, in addition to in utero and lactational exposure before elimination (Crum et al. 1993) bData presented as mean + standard error. Number in parentheses is percent reduction from value at day 0. Sample size is three pooled samples of three mink kits c Means within same column for each prior dietary treatment with different superscripts are significantly different (p < 0.05) dControl diet fed ad libitum e Control diet containing 10% mineral oil fed at 45% of ad libitum consumption

M O / R diets, respectively. Day 21 body burdens were significantly reduced in the 6.25 mg/kg kits fed the A L and M O / R diet when compared to day 0 values (Table 4). Heptochlor epoxide body burdens decreased by 93 and 96% in kits fed the AL or M O / R diets, respectively, with similar decreases in wholebody HE concentrations (95 and 96%, respectively). The halflives of HE in the kits was also similar; approximately 5 days for the AL and M O / R kits, using either HE body burdens or whole-body H E concentrations. Body fat content increased significantly in the developing control kits fed the AL diet, but was significantly reduced in kits fed the M O / R diet when compared to control kit percentages at day 0 of elimination (Table 4). At day 21 of elimination, kits from the 6.25 mg/kg group fed the M O / R diet had body fat percentages that were significantly below body fat percentages in the 6.25 mg/kg kits fed the AL diet.

Discussion Feed consumption by the 6.25 mg/kg adult female mink fed the AL diet, on a body weight basis (157 g/kg bw/day), was comparable with intake values reported for female mink by Bleavins and Aulerich (1981). Crum et al. (1993) also reported similar values; 148 and 154 g/kg bw/day for female mink fed control and 6.25 mg/kg heptachlor diets, respectively. Feed intake during the elimination period by the control females fed the AL diet was considerably below these values. Mink in good health are generally less active during warm temperatures; thus, their feed intake decreases in response to lower energy requirements. The consistency in daily feed intake by the 6.25 mg/kg animals may reflect an attempt to regain weight that was lost during the previous heptachlor feeding trial (Crum et al. 1993). Kit feed consumption was apparently unaffected by previous exposure

Elimination of Heptachlor Epoxide from Mink

to heptachlor, since both the former control and 6.25 mg/kg kits consumed similar amounts of feed during the 21-day period. Restricting feed intake by 45% of AL intake caused considerable weight loss in adult female and kit mink from both the control and 6.25 mg/kg groups. Since dietary mineral oil alone has not been shown to affect the body weight of sheep and rats (Rozman et al. 1982a; Polin et al. 1991), and feed restriction alone caused reductions in body weight of rats (Wyss et al. 1982; Polin et al. 1991), it is believed that body weight loss of mink in this study was due to restricting dietary intake. Prior exposure to 6.25 mg heptachlor/kg diet did not result in an increased effect on body weight loss in mink administered the MO/R diet. The percent weight loss of the surviving 6.25 mg/kg females fed the MO/R diet was similar to that of the control females on the same diet (22 vs 25%). Although day 0 body weights were not recorded for kit mink, the day 21 body weights for control and 6.25 mg/kg kits administered the MO/R treatment were very similar, indicating that prior exposure to heptachlor did not cause an increased effect on body weight loss during the elimination period. Experiments conducted on rats placed on a similar elimination diet also indicated no differences in body weight loss between control rats and rats previously exposed to polybrominated biphenyls (PBBs) (Polin et al. 1991). Although consumption of the MO/R diet caused considerable reductions in body fat content over the 21-day trial in adult female and kit mink from both prior treatment groups, lower body fat percentages could not be associated with increased reductions in HE body burdens or whole-body HE concentrations. Since mink displayed no substantial differences in HE body burdens or whole-body HE concentrations whether fed the AL or MO/R diet, but had considerably different body fat percentages, restricting dietary intake to mobilize fat does not appear necessary to achieve substantial removal of HE from mink. Overall, removal of HE was more extensive and rapid in kit mink than in adults, particularly in the 6.25 mg/kg kits which experienced a near 100% reduction in HE body burdens and whole-body concentrations of HE. Consumption of the AL or MO/R diets by the 6.25 mg/kg kits for 21 days resulted in an approximate 15% greater increase in HE removal compared to percent reduction values in the 6.25 mg/kg adult females fed these diets, while the half-life of HE in these kits was 50% of the adult value. This may have been due to the shorter exposure duration of the kits to heptachlor prior to the elimination period, as compared to the adult females which had been consuming 6.25 mg heptachlor/kg diet for 181 days before the elimination trial. It is also conceivable that natural growth and development of the kits during the elimination period of the present study could have resulted in larger and faster HE reductions compared to adults. Consumption of the AL or MO/R diets by the 6.25 mg/kg kits decreased whole-body HE concentrations below concentrations determined at birth in kits whelped from dams fed 6.25 mg heptachlor/kg diet prior to and during gestation (Crum et al. 1993). However, HE body burdens were still much greater than the body burdens of newborn kits, but were comparable to amounts in kits from this group at three weeks of age. This suggests that HE is readily mobilized and eliminated from the bodies of kit mink, and that the magnitude of adverse effects, such as decreased postnatal growth (Crum et al. 1993), could be reduced in a relatively short time span simply through consumption of a heptachlor-free diet.

379 Acknowledgments. This research was supported by Grant No. HHHERP88-04 of the Hawaii Heptachlor Research and Education Foundation and by the Michigan State University Agricultural Experiment Station. The authors would like to thank Ivy Su and Andy Holaday for performing the chemical analyses, and Natalie Biondo, Angelo Napolitano, Chris Bush, and Phil Summer for their technical assistance.

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