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Metabolism of insecticides, VIII (1): Excretion, distribution and metabolism of α-chlordan-14C by rats
Life Sciences Yol . 3, pp . 1497-1500, 1984. Pergamon Press, Inc . Printed in the United States.
METABOLISM OF INSECTICIDES, VIII (1) EXCRETION, DLSTRIBUTION AND METABOLISM OF a-CHLORDAN- 14C BY RATS N . H. Poonawalla and F . Korte Organisch-Chemisches Institut, Universität Bonn (Received 5 October 1984) By previous studies with 14C-labelled drin-insecticides, it was known that microorganisms as well as mosquito larvae (Aedes aegypti) metabolize them to more hydrophilic products which are excreted into the aqueous phase (2-4) . The present work is concerned with the distribution and excretion of a-chlordan and its metabolites by rata. Method For these studies, each of the 4 male Wistar rats received an intravenous dose of 27 F+g of chlordan- 14C (spec . activity 8 .4 mC/mMol) . The animals were kept in individual metabolism cages . After 6o hours, the animals were sacrificed, and their excreta, carcasses, viscera and other tissues were homogenized and extracted separately (1) . Quantitative estimation of radioactivity in different tissues was made by counting in a lead chamber the activity emitted by an aliquot of each extract. For qualitative analyses paperchromatography (mobile phase + N. H. Poonawalla ~rishes to express his sincere thanks to Dr . G. Ludwig (Shell Grundlagenforschung-Gesellschaft m . b. H. , Schloss Birlinghoven) for his helpful guidance. Present address : Shell Development Company Modeato, Cal . , USA . 1497
1498
METAHOLiSM OF INSECTICIDES
Vol . 3, No. 12
methanol/water (97 : 3), paper impregnated with 5 % vaseline oil - Rfvalues : a-chlordan o .45, hydrophilic metabolite o .82) and thin-layer chromatography (silica gel G according to Stahl from E. Merck - mobile phase : n-hexane, Rf-values : a-chlordan o .40, hydrophilic metabolite o .lo) were used . Results All results are based on the mean value of four animals . Excretion Within 6o hours 29 9b of the total injected radioactivity were excreted in the faeces - consisting mainly of hydrophilic metabolite - , while only 1
°Jo
was excreted in urine.
Distribution A high percentage of radioactivity was found in fatty tissues and in the alimentary canal . A detailed survey of the distribution of radioactivity found in different tissues is given in table I. The percentages shown for fatty tissues, muscles and carcass are not absolute values, as the carcass still contained large amounts of fatty tissues and muscles .
The recovery of
radioactivity amounts to 98 % of the total injected dose . For exact evaluation of the percentage distribution, also the values for concentration of radioactivity (counts/min . per 1 g of tissue) are given in table I . The highest concentration was found in the contents of stomach (0.9 ppm) and abdominal fat (0.49 ppm) . Metabolism Analyses showed that ?5 % of the radioactivity found in the faeces consisted of hydrophilic metabolism products . This means that within 60 hours, 22 qô of the total injected a-chlordan were excreted in the form of
Vol . 3, No. 12
META130LISM OF INBECTICTDEB
1499
Table I Excretion and Distribution of a-Chlordan- 14C and its Metabolites after Intravenous Administration Analyses a b
A
B
C
Stomach + Duodenum
l .05
0.6
380
30
70
Contents of stomach
o.57
1. 9
2100
25
75
Gut
6.31
5 .7
570
40
60
Contents of gut
7. 21
9 .8
860
25
75
Abdominal fat
6 .57
11.9
1140
35
65
11.28
7 .0
390
loo
--
2.16
1.2
370
30
70
Liver
11.11
1.6
90
85
15
Muscles
55.50
1.7
20
90
10
Spleen
1. lo
< o.l
<30
--
--
Testes
3.20
< o.l
<20
--
--
Heart
o.95
< o.l
<30
--
--
Lungs
1.25
0 .l
80
--
--
Brain
1.43
0 .l
28 .65
__
70 __
-__
-__
9 . lo
< o.l
Qo
--
--
56 .89
26 .2
290
95
5
29.2
850
25
75
1 .1
30
20
80
Subcutaneous fat Kidneys
Skin Blood Carcass Faeces Urine Total
204 .2
>98 .4
A = weight of tissue in g. B = % of radioactivity administered C = concentration counts/min . per 1 g. tissue 233o counts/min . ... l.o ppm.
a = % unchanged a-chlordan b = % hydrophilic metabolites
hydrophilic metabolites . High percentages of hydrophilic metabolites were also detected in the entire alimentary tract and in the kidneys, as can be seen in table I. Unchanged a-chlordan was found only in the subcutaneous fat .
1500
METAHOLI3M OF INSECTICD~ES
Yol . 3, No. 12
Summary After intravenous administration male rats excrete 30 % of the injected 27 pg of a-chlordan -14 C, most of which was found to have been metabolized . The alimentary tract contained a high percentage of metabo lites, whereas unchanged a-chlordan was found in subcutaneous fat only. References 1.
Metabolism of Insecticides, VII : G. LUDWIG, J. WEIS and F . KÖRTE, Life Sciences 3, 123 (1964)
2.
F. KÖRTE, G . LUDWIG and J. VOGEL, Liebigs Ann . Chem. _65__6, 135 (1962)
3.
F. KÖRTE and M . STIASNI, Liebigs Ann . Chem. 673, 146 (1964)
4.
F. KÖRTE, G . LUDWIG, J . VOGEL, M. STIASNI, G. RECHMEIER and W . KOCHEM, Vth International Pesticide ConBrese, London 1963
METABOLISM OF INSECTICIDES, VIII (1) EXCRETION, DLSTRIBUTION AND METABOLISM OF a-CHLORDAN- 14C BY RATS N . H. Poonawalla and F . Korte Organisch-Chemisches Institut, Universität Bonn (Received 5 October 1984) By previous studies with 14C-labelled drin-insecticides, it was known that microorganisms as well as mosquito larvae (Aedes aegypti) metabolize them to more hydrophilic products which are excreted into the aqueous phase (2-4) . The present work is concerned with the distribution and excretion of a-chlordan and its metabolites by rata. Method For these studies, each of the 4 male Wistar rats received an intravenous dose of 27 F+g of chlordan- 14C (spec . activity 8 .4 mC/mMol) . The animals were kept in individual metabolism cages . After 6o hours, the animals were sacrificed, and their excreta, carcasses, viscera and other tissues were homogenized and extracted separately (1) . Quantitative estimation of radioactivity in different tissues was made by counting in a lead chamber the activity emitted by an aliquot of each extract. For qualitative analyses paperchromatography (mobile phase + N. H. Poonawalla ~rishes to express his sincere thanks to Dr . G. Ludwig (Shell Grundlagenforschung-Gesellschaft m . b. H. , Schloss Birlinghoven) for his helpful guidance. Present address : Shell Development Company Modeato, Cal . , USA . 1497
1498
METAHOLiSM OF INSECTICIDES
Vol . 3, No. 12
methanol/water (97 : 3), paper impregnated with 5 % vaseline oil - Rfvalues : a-chlordan o .45, hydrophilic metabolite o .82) and thin-layer chromatography (silica gel G according to Stahl from E. Merck - mobile phase : n-hexane, Rf-values : a-chlordan o .40, hydrophilic metabolite o .lo) were used . Results All results are based on the mean value of four animals . Excretion Within 6o hours 29 9b of the total injected radioactivity were excreted in the faeces - consisting mainly of hydrophilic metabolite - , while only 1
°Jo
was excreted in urine.
Distribution A high percentage of radioactivity was found in fatty tissues and in the alimentary canal . A detailed survey of the distribution of radioactivity found in different tissues is given in table I. The percentages shown for fatty tissues, muscles and carcass are not absolute values, as the carcass still contained large amounts of fatty tissues and muscles .
The recovery of
radioactivity amounts to 98 % of the total injected dose . For exact evaluation of the percentage distribution, also the values for concentration of radioactivity (counts/min . per 1 g of tissue) are given in table I . The highest concentration was found in the contents of stomach (0.9 ppm) and abdominal fat (0.49 ppm) . Metabolism Analyses showed that ?5 % of the radioactivity found in the faeces consisted of hydrophilic metabolism products . This means that within 60 hours, 22 qô of the total injected a-chlordan were excreted in the form of
Vol . 3, No. 12
META130LISM OF INBECTICTDEB
1499
Table I Excretion and Distribution of a-Chlordan- 14C and its Metabolites after Intravenous Administration Analyses a b
A
B
C
Stomach + Duodenum
l .05
0.6
380
30
70
Contents of stomach
o.57
1. 9
2100
25
75
Gut
6.31
5 .7
570
40
60
Contents of gut
7. 21
9 .8
860
25
75
Abdominal fat
6 .57
11.9
1140
35
65
11.28
7 .0
390
loo
--
2.16
1.2
370
30
70
Liver
11.11
1.6
90
85
15
Muscles
55.50
1.7
20
90
10
Spleen
1. lo
< o.l
<30
--
--
Testes
3.20
< o.l
<20
--
--
Heart
o.95
< o.l
<30
--
--
Lungs
1.25
0 .l
80
--
--
Brain
1.43
0 .l
28 .65
__
70 __
-__
-__
9 . lo
< o.l
Qo
--
--
56 .89
26 .2
290
95
5
29.2
850
25
75
1 .1
30
20
80
Subcutaneous fat Kidneys
Skin Blood Carcass Faeces Urine Total
204 .2
>98 .4
A = weight of tissue in g. B = % of radioactivity administered C = concentration counts/min . per 1 g. tissue 233o counts/min . ... l.o ppm.
a = % unchanged a-chlordan b = % hydrophilic metabolites
hydrophilic metabolites . High percentages of hydrophilic metabolites were also detected in the entire alimentary tract and in the kidneys, as can be seen in table I. Unchanged a-chlordan was found only in the subcutaneous fat .
1500
METAHOLI3M OF INSECTICD~ES
Yol . 3, No. 12
Summary After intravenous administration male rats excrete 30 % of the injected 27 pg of a-chlordan -14 C, most of which was found to have been metabolized . The alimentary tract contained a high percentage of metabo lites, whereas unchanged a-chlordan was found in subcutaneous fat only. References 1.
Metabolism of Insecticides, VII : G. LUDWIG, J. WEIS and F . KÖRTE, Life Sciences 3, 123 (1964)
2.
F. KÖRTE, G . LUDWIG and J. VOGEL, Liebigs Ann . Chem. _65__6, 135 (1962)
3.
F. KÖRTE and M . STIASNI, Liebigs Ann . Chem. 673, 146 (1964)
4.
F. KÖRTE, G . LUDWIG, J . VOGEL, M. STIASNI, G. RECHMEIER and W . KOCHEM, Vth International Pesticide ConBrese, London 1963