46,663-669(1978)
TOXlCOLOGYANDAPPLIEDPHARMACOLOGY
Concentration of DDT and DDE in Plasma and Subcutaneous Adipose Tissue before and after Intestinal Bypass Operation for Treatment of Obesity L. BACKMAN'AND Department
of Surgery,
Serafimerlasarettet
Received
January
B. KOLMODIN-HEDMAN
and Division of Occupational Stockholm, Sweden I?, 1978:
accepted
April
Medicine,
Karolinska
sjukhusei,
13.1978
Concentration of DDT and DDE in Plasma and Subcutaneous Adipose Tissue before and after Intestinal Bypass Operation for Treatment of Obesity. BACKMAN, L., AND KOLMODINHEDMAN, B. (1978). Toxicol. Appl. Pharmacol. 46, 663-669. DDT and its principal metabolite, DDE, are stored mainly in body fat. In spite of a general prohibition in household use in 1970, the gene& population in Sweden is still exposed to these pesticides in the diet. The aim of this study was to examine whether weight loss is followed by increased concentrations of the pesticides in adipose tissue and plasma and whether increased concentrations could possibly explain some unusual neurological symptoms observed in some patients after a shunt operation. Eight subjects were examined before and 1 year after jejune-ileostomy. The mean weight loss was 46.9 F 2.8 kg (2 + SE). The concentrations ofp, p’-DDE in plasma increased significantly from 5.1 k 0.9 to 8.2 + 1.3 r&ml during the weight loss. This concentration is still well below the concentration in a control group of nonexposed office personnel whose mean concentration is 19 k 4.0 rig/ml. In adipose tissue the mean concentrations ofp,p’-DDT andp,p’-DDE increased from 390 & 65 to 526 + 107 rig/g and 863 + 136 to 1341 f 194 rig/g, respectively. The ratio of DDE: DDT increased in all but one subject, indicating an increased metabolism of DDT after the operation. The calculated total body content of DDT and DDE decreased in all but two patients after the bypass operation due to increased metabolism and excretion. The risk of DDT intoxication following an intestinal bypass operation appears to be small.
DDT (l,l, 1-trichloro-2,2-bis(p-chlorophenyl)ethane) and its metabolites have a high affinity for fat, and a low rate of metabolism (Hayes et al., 197 1). This means that after cessation of even a very moderate exposure, DDT will remain in the body fat for a long time. The household use of DDT in Sweden was prohibited in 1970. However, some still contains (l,l-dichloro-2,2-bis(pimported food DDT and DDE chlorophenyl)ethene) (Noren and Rosen, 1976; West% et al., 1970, 1971) and therefore a low degree exbosure to these pesticides continues. In rats previously fed high levels of DDT in the diet, mobilization of fat resulted in an increase in the concentration of DDT and its metabolites in adipose tissue and plasma after a period of 10 days partial starvation (Fitzhugh and Nelson, 1977; Dale et al., 1 Address requests for reprints to L. Backman, M.D., Department of Surgery, Serafimerlasarettet, S-I 12 83 Stockholm, Sweden.
663
0041-M)8X/78/0463-0663%02.00/O Copyright 0 1978 by Academic Press. Inc. AU rights of reproduction in any form reserved. Printed in Great Britain
664
BACKMANANDKOLMODIN-HEDMAN
1962). No information is available on the effect of bodyweight reduction on DDT concentration in man. Obese patients subjected to a small intestinal-shunt operation lose a considerable amount of fat. In some of the subjects symptoms of neuromyopathia, verified electromyographically (EMG), have appeared. Several explanations exist for this complication, e.g., deficiency of essential fatty acids (Ciongoli and Poser, 1972) or electrolyte disturbances (Backman and Hallberg, 1975). Another explanation would be DDT intoxication (Drenth et al., 1972), which has been associated with EMG changes. The purpose of the present study was to examine whether obese subjects because of a supposed hyperphagia have higher plasma and fat concentration of p,p’-DDT or its principal metabolite, p,p’-DDE, than Swedes in general, We also wished to examine whether mobilization of fat during weight loss would result in an increased concentration of DDT and DDE in fat and plasma, and whether neurological symptoms might appear as result of any such increase. METHODS Eight subjects, five women and three men each subjected to a small intestinal bypass as treatment for their massive obesity were studied. Data on the subjects are shown in Table 1. The bypass operation was either a modified end-to-side jejuno-ileostomy (L. Backman, B. Swane, and D. Hallberg, unpublished observations) or a modified end-toend jejuno-ileostomy with anti-reflux-valve ileocecostomy (Hallberg et al., 1975). The main weight loss after the operation occurs during the first year (Backman, 1975). In most cases it is constant, and, therefore, it is expressed as the change in body weight index (Broca) per week (Hallberg and Backman, 1973). For the determination of DDT and DDE a blood sample was obtained from a peripheral vein, and a fat sample was obtained from the subcutaneous tissue near the abdominal incision at the time of the operation. This sampling was repeated after 1 year, the fat sample being taken from the same area as before. In five persons blood was also sampled 3 months after the operation. DDT and DDE were assayed by a gas chromatographic procedure described by Palmer and Kolmodin-Hedman (1972). The limit of detection for plasma p,p’-DDT was 3.0 rig/ml and that of p,p’-DDE was 1.0 rig/ml. The coefficient of variation was 10 to 20%. The coefficient of variation for p,p’-DDT at 400 rig/g fat was 5.1%, and that for p,p’-DDE at 800 rig/g fat was 8.4%.
TABLE
1
CLINICAL DATA (.% + SE) ON EIGHT SUWECTS BEFORE INTESTINAL BYPASS OPERATION FOR TREATMENT OF OBESITY
Body weight (kg) Body weight (cm) Age (years)
137.2 & 7.7 167.8 ? 3.6 38.5 & 3.4
(Range 108.5-155.5) (Range 154-183) (Range 21-52)
DDT
IN PLASMA
AND
FAT IN OBESE
665
PATIENTS
No drugs which stimulate liver microsomal oxidases, such as phenobarbital were taken by the patients. The fat samples were kept frozen. The tissue was homogenized by means of an Ultra Thurrax (Janke SC Kunkel KG, ICA Werk Staufen i. Breisgau) and extracted into hexane. Heptachlorepoxide (1,4,5,6,7,8,8-heptachloro-2,3-epoxy-3a,4,7a-tetrahydro-4,7methanoindan) was used as internal standard. The blood samples were drawn into heparinized tubes and centrifuged at 2300 rpm x min-‘. The plasma was kept frozen at -18°C until analyzed. The weight of body fat before and after the operation was calculated according to Scott et al. (1975). Total amounts of DDT and DDE in fat were calculated by multiplying the weight of body fat by the respective concentration in fat.
RESULTS
The changes in body weight and body fat content are shown in Table 2. The concentration of p,p’-DDE in plasma and fat increased significantly (p < 0.05). The p,p’-DDT concentration was essentially unchanged after the operation (Tables 3 and 4). The ratio DDE/DDT in fat increased after the weight loss in all but one subject (KA) (Table 4). This increase was not statistically significant. The calculated total amounts of p,p’-DDT and p,p’-DDE in body fat were lower postoperatively in all but two individuals (Table 2). One of these subjects (BJ) lives in the Stockholm archipeiago during most of the year where he consumes a considerable amount of fish, containing high levels of DDT (Kolmodin-Hedman, 1974). The other (PH) had the lowest fat concentration of both DDT and DDE in the series before the operation, and he was the youngest and the heaviest person in the series.
TABLE
2
CHANGESIN SOMEPARAMETERS AFTERSMALLINTESTINAL-SHUNT OPERATION FORTREATMENTOFOBESITYINEIGHTSUBJECTS
Body weight Subject (kg)
Body fat (kg)
DDE
DDT
DDE
DDT
concentration fat bdd
concentration fat bdd
contentin
contentin
fat (md
fat (w)
-0.13 -42.62 -8.65 +5.28
-9.45 -19.83 -9.39
KA
-51
GG HH PH BJ OT IA BC x + SE
-45.5 -53.4 -51 -40 -32 -48.2 -48
-41.9 -42.1 -42.2 -49.4 -33.9 -30.7 -43.6 -43.2
+181 +266 +594 +106 i52 -151
-46.9 2.8
-40.9 2.1
+136.8 89.1
+241
-201
+381 -206 +929 +414 +1256 +363 i475 +151 +411.9 158.5
+ 1.11 -3.92 -14.52 -20.82 -10.5 5.5
+9.91 +11.27
-1.33 -14.24 -13.93 -14.1
10.0
666
BACKMAN
AND
KOLMODIN-HEDMAN
TABLE PLASMA
p,p’-DDT BYPASS
3
CONCENTRATION (rig/ml) OF p&-DDE AND BEFORE AND AFTER SMALL INTESTINAL OPERATION FOR TREATMENT OF OBESITY M EIGHT SUBJECTS
Preoperative Subject
Postoperative
DDE
DDT
DDE
DDT
KA GG HH PEH BJ OT IA BC
3.0 9.5 3.8 2.0 7.0 7.5 5.0 3.0
(3.0 4.5 (3.0
TOXlCOLOGYANDAPPLIEDPHARMACOLOGY
Concentration of DDT and DDE in Plasma and Subcutaneous Adipose Tissue before and after Intestinal Bypass Operation for Treatment of Obesity L. BACKMAN'AND Department
of Surgery,
Serafimerlasarettet
Received
January
B. KOLMODIN-HEDMAN
and Division of Occupational Stockholm, Sweden I?, 1978:
accepted
April
Medicine,
Karolinska
sjukhusei,
13.1978
Concentration of DDT and DDE in Plasma and Subcutaneous Adipose Tissue before and after Intestinal Bypass Operation for Treatment of Obesity. BACKMAN, L., AND KOLMODINHEDMAN, B. (1978). Toxicol. Appl. Pharmacol. 46, 663-669. DDT and its principal metabolite, DDE, are stored mainly in body fat. In spite of a general prohibition in household use in 1970, the gene& population in Sweden is still exposed to these pesticides in the diet. The aim of this study was to examine whether weight loss is followed by increased concentrations of the pesticides in adipose tissue and plasma and whether increased concentrations could possibly explain some unusual neurological symptoms observed in some patients after a shunt operation. Eight subjects were examined before and 1 year after jejune-ileostomy. The mean weight loss was 46.9 F 2.8 kg (2 + SE). The concentrations ofp, p’-DDE in plasma increased significantly from 5.1 k 0.9 to 8.2 + 1.3 r&ml during the weight loss. This concentration is still well below the concentration in a control group of nonexposed office personnel whose mean concentration is 19 k 4.0 rig/ml. In adipose tissue the mean concentrations ofp,p’-DDT andp,p’-DDE increased from 390 & 65 to 526 + 107 rig/g and 863 + 136 to 1341 f 194 rig/g, respectively. The ratio of DDE: DDT increased in all but one subject, indicating an increased metabolism of DDT after the operation. The calculated total body content of DDT and DDE decreased in all but two patients after the bypass operation due to increased metabolism and excretion. The risk of DDT intoxication following an intestinal bypass operation appears to be small.
DDT (l,l, 1-trichloro-2,2-bis(p-chlorophenyl)ethane) and its metabolites have a high affinity for fat, and a low rate of metabolism (Hayes et al., 197 1). This means that after cessation of even a very moderate exposure, DDT will remain in the body fat for a long time. The household use of DDT in Sweden was prohibited in 1970. However, some still contains (l,l-dichloro-2,2-bis(pimported food DDT and DDE chlorophenyl)ethene) (Noren and Rosen, 1976; West% et al., 1970, 1971) and therefore a low degree exbosure to these pesticides continues. In rats previously fed high levels of DDT in the diet, mobilization of fat resulted in an increase in the concentration of DDT and its metabolites in adipose tissue and plasma after a period of 10 days partial starvation (Fitzhugh and Nelson, 1977; Dale et al., 1 Address requests for reprints to L. Backman, M.D., Department of Surgery, Serafimerlasarettet, S-I 12 83 Stockholm, Sweden.
663
0041-M)8X/78/0463-0663%02.00/O Copyright 0 1978 by Academic Press. Inc. AU rights of reproduction in any form reserved. Printed in Great Britain
664
BACKMANANDKOLMODIN-HEDMAN
1962). No information is available on the effect of bodyweight reduction on DDT concentration in man. Obese patients subjected to a small intestinal-shunt operation lose a considerable amount of fat. In some of the subjects symptoms of neuromyopathia, verified electromyographically (EMG), have appeared. Several explanations exist for this complication, e.g., deficiency of essential fatty acids (Ciongoli and Poser, 1972) or electrolyte disturbances (Backman and Hallberg, 1975). Another explanation would be DDT intoxication (Drenth et al., 1972), which has been associated with EMG changes. The purpose of the present study was to examine whether obese subjects because of a supposed hyperphagia have higher plasma and fat concentration of p,p’-DDT or its principal metabolite, p,p’-DDE, than Swedes in general, We also wished to examine whether mobilization of fat during weight loss would result in an increased concentration of DDT and DDE in fat and plasma, and whether neurological symptoms might appear as result of any such increase. METHODS Eight subjects, five women and three men each subjected to a small intestinal bypass as treatment for their massive obesity were studied. Data on the subjects are shown in Table 1. The bypass operation was either a modified end-to-side jejuno-ileostomy (L. Backman, B. Swane, and D. Hallberg, unpublished observations) or a modified end-toend jejuno-ileostomy with anti-reflux-valve ileocecostomy (Hallberg et al., 1975). The main weight loss after the operation occurs during the first year (Backman, 1975). In most cases it is constant, and, therefore, it is expressed as the change in body weight index (Broca) per week (Hallberg and Backman, 1973). For the determination of DDT and DDE a blood sample was obtained from a peripheral vein, and a fat sample was obtained from the subcutaneous tissue near the abdominal incision at the time of the operation. This sampling was repeated after 1 year, the fat sample being taken from the same area as before. In five persons blood was also sampled 3 months after the operation. DDT and DDE were assayed by a gas chromatographic procedure described by Palmer and Kolmodin-Hedman (1972). The limit of detection for plasma p,p’-DDT was 3.0 rig/ml and that of p,p’-DDE was 1.0 rig/ml. The coefficient of variation was 10 to 20%. The coefficient of variation for p,p’-DDT at 400 rig/g fat was 5.1%, and that for p,p’-DDE at 800 rig/g fat was 8.4%.
TABLE
1
CLINICAL DATA (.% + SE) ON EIGHT SUWECTS BEFORE INTESTINAL BYPASS OPERATION FOR TREATMENT OF OBESITY
Body weight (kg) Body weight (cm) Age (years)
137.2 & 7.7 167.8 ? 3.6 38.5 & 3.4
(Range 108.5-155.5) (Range 154-183) (Range 21-52)
DDT
IN PLASMA
AND
FAT IN OBESE
665
PATIENTS
No drugs which stimulate liver microsomal oxidases, such as phenobarbital were taken by the patients. The fat samples were kept frozen. The tissue was homogenized by means of an Ultra Thurrax (Janke SC Kunkel KG, ICA Werk Staufen i. Breisgau) and extracted into hexane. Heptachlorepoxide (1,4,5,6,7,8,8-heptachloro-2,3-epoxy-3a,4,7a-tetrahydro-4,7methanoindan) was used as internal standard. The blood samples were drawn into heparinized tubes and centrifuged at 2300 rpm x min-‘. The plasma was kept frozen at -18°C until analyzed. The weight of body fat before and after the operation was calculated according to Scott et al. (1975). Total amounts of DDT and DDE in fat were calculated by multiplying the weight of body fat by the respective concentration in fat.
RESULTS
The changes in body weight and body fat content are shown in Table 2. The concentration of p,p’-DDE in plasma and fat increased significantly (p < 0.05). The p,p’-DDT concentration was essentially unchanged after the operation (Tables 3 and 4). The ratio DDE/DDT in fat increased after the weight loss in all but one subject (KA) (Table 4). This increase was not statistically significant. The calculated total amounts of p,p’-DDT and p,p’-DDE in body fat were lower postoperatively in all but two individuals (Table 2). One of these subjects (BJ) lives in the Stockholm archipeiago during most of the year where he consumes a considerable amount of fish, containing high levels of DDT (Kolmodin-Hedman, 1974). The other (PH) had the lowest fat concentration of both DDT and DDE in the series before the operation, and he was the youngest and the heaviest person in the series.
TABLE
2
CHANGESIN SOMEPARAMETERS AFTERSMALLINTESTINAL-SHUNT OPERATION FORTREATMENTOFOBESITYINEIGHTSUBJECTS
Body weight Subject (kg)
Body fat (kg)
DDE
DDT
DDE
DDT
concentration fat bdd
concentration fat bdd
contentin
contentin
fat (md
fat (w)
-0.13 -42.62 -8.65 +5.28
-9.45 -19.83 -9.39
KA
-51
GG HH PH BJ OT IA BC x + SE
-45.5 -53.4 -51 -40 -32 -48.2 -48
-41.9 -42.1 -42.2 -49.4 -33.9 -30.7 -43.6 -43.2
+181 +266 +594 +106 i52 -151
-46.9 2.8
-40.9 2.1
+136.8 89.1
+241
-201
+381 -206 +929 +414 +1256 +363 i475 +151 +411.9 158.5
+ 1.11 -3.92 -14.52 -20.82 -10.5 5.5
+9.91 +11.27
-1.33 -14.24 -13.93 -14.1
10.0
666
BACKMAN
AND
KOLMODIN-HEDMAN
TABLE PLASMA
p,p’-DDT BYPASS
3
CONCENTRATION (rig/ml) OF p&-DDE AND BEFORE AND AFTER SMALL INTESTINAL OPERATION FOR TREATMENT OF OBESITY M EIGHT SUBJECTS
Preoperative Subject
Postoperative
DDE
DDT
DDE
DDT
KA GG HH PEH BJ OT IA BC
3.0 9.5 3.8 2.0 7.0 7.5 5.0 3.0
(3.0 4.5 (3.0
