Metabolism and excretion of dimethoate following ingestion of overtolerance peas and a bolus dose

Data to guide an exposure assessment were obtained by giving sugar peas containing overtolerance dimethoate residues (17 ppm; 8% oxon) and a bolus dose of dimethoate to a healthy adult male. The dimethoate tolerance on peas was and remains 2 ppm. Serial total urine samples were collected and analysed for dimethoate and its oxon, dimethylphosphate, dimethylphosphorothioate (DMTP) and dimethylphosphorodithioate. The dose of dimethoate administered was approx. 0.1 mg/kg body weight and produced no symptoms of toxicity. Dimethylphosphates appeared in the urine within 2 hr. The major metabolite (about 60%) was DMTP. Only traces (< 0.5%) of dimethoate and oxon were recovered from urine. Acetylcholinesterase inhibition was not observed although urinary metabolites were prominent, indicating that they are better indicators of acute exposure than cholinesterase inhibition. The results obtained using a bolus dose were virtually identical to those from the trial with overtolerance peas, and indicated that dimethoate is readily absorbed and its urinary metabolites are readily eliminated following exposures to low doses (0.1 mg/kg body weight).     

D-penicillamine metabolism in neurodegenerative diseases: an in vivo/in vitro sulphydryl methylation study

1. D-Penicillamine (125 mg) was administered orally to control (healthy volunteers), Parkinson's and Motor Neurone Disease patients following an overnight fast. 2. Blood was collected at 08:00 h for the preparation of red blood cell membranes used in the in vitro S-methylation studies. Urine was collected from 08:00 to 16:00 h and analysed for D-penicillamine and its metabolites. 3. Metabolism occurred via S-methylation, N-acetylation and disulphide formation. Both the Parkinson's and Motor Neurone Disease patients excreted significantly higher median levels of S-methyl-D-penicillamine in the urine than the controls (177 and 209% more for the Parkinson's and Motor Neurone Disease patients respectively). 4. The in vitro and in vivo production of S-methyl-D-pencillamine was highly correlated in the control (rs = 0.936), Parkinson's (0.986) and Motor Neurone Disease (0.752) populations.     

Stereoselective epoxidation of arachidonic acid by cytochrome P-450s 2CAA and 2C2

In the present study, we determined the stereoselective epoxidation of arachidonic acid by cytochrome P-450 (P-450) 2CAA and P-450 2C2, two arachidonic acid epoxygenases found in rabbit renal cortex, by chiral normal-phase high-performance liquid chromatography (HPLC)-analysis. Purified P-450 2CAA reconstituted with P-450 oxidoreductase, lipid and cytochrome b5 or microsomes isolated from COS-1 cells expressing P-450 2C2 were incubated in the presence of [1-14C]arachidonic acid. The epoxide metabolites 14,15- and 11,12-epoxyeicosatrienoic acids (EETs) were purified by reverse-phase HPLC and derivatized to methyl (14,15-EET) and pentafluorobenzyl (11,12-EET) esters. Enantiomers of 14,15-EET-methyl ester and 11,12-EET-pentafluorobenzyl ester were resolved on Chiralcel OB and OD columns, respectively, with a mobile phase of 0.15% 2-propanol in n-hexane. P-450 2CAA and P-450 2C2 produce 11,12- and 14,15-EETs in distinct ratios but are equally stereoselective at the 11,12-position. P-450 2CAA produced 11(S), 12(R)-EET with 63% stereoselectivity, and P-450 2C2 produced the same enantiomer with 61% stereoselectivity. Both enzymes are also stereoselective at the 14,15- position, preferentially producing the 14(R), 15(S)-EET. P-450 2CAA produces this enantiomer with 72% selectivity, and P-450 2C2 produces it with 62% selectivity. The results of this study indicate that P-450 2CAA and P-450 2C2 are not only regioselective but also exhibit a high degree of stereoselectivity.     

Structure and epitope characterisation of the O-specific polysaccharide of Proteus mirabilis O28 containing amides of D-galacturonic acid with L-serine and L-lysine

The O-specific polysaccharide of Proteus mirabilis O28 was found to contain D-galactose, D-galacturonic acid (GalA), 2-acetamido-2-deoxy-D-glucose, L-serine, L-lysine, and O-acetyl groups in molar ratios 1:2:1:1:1:1, the amino acids being linked via their alpha-amino group to the carboxyl group of GalA. The polysaccharide was studied using 1H- and 13C-NMR spectroscopy, including selective spin-decoupling, one-dimensional total correlation spectroscopy, two-dimensional homonuclear correlation spectroscopy (COSY), heteronuclear 13C,1H COSY, one-dimensional NOE, and two-dimensional rotating-frame NOE spectroscopy and partial acid hydrolysis followed by borohydride reduction, methylation, and GLC/MS analysis of the derived glycosyl alditols. The following structure of the repeating unit was established: [formula: see text] Epitope specificity of the P. mirabilis O28 polysaccharide was analysed using a homologous rabbit polyclonal antiserum in quantitative precipitation, passive immunohemolysis, and inhibition of passive immunohemolysis. Study with related synthetic glycopolymers (2-acrylamidoethyl glycosides of amides of alpha-D-GalA with amino acids copolymerised with acrylamide) showed the importance of D-GalA(L-Lys) for manifesting serological specificity of the O-antigen. Serological cross-reactions between P. mirabilis O28, S1959, and R14/S1959 (a transient-like form) are discussed.     

二元碱度和Al_2O_3对CaO-SiO_2-FeO-Fe_2O_3-P_2O_5-Al_2O_3-MgO-MnO钢渣中磷酸盐富集的影响

以八元CaO-SiO_2-FeO-Fe_2O_3-P_2O_5-Al_2O_3-MgO-MnO钢渣体系为研究对象,结合热力学计算和实验检测,分析了二元碱度B和Al_2O_3含量对八元钢渣系中磷酸盐富集行为的影响。结果表明:钢渣二元碱度和Al_2O_3含量直接影响钢渣中f-C2S的生成量,进而影响磷酸盐富集相nC_2S-C_3P内P_2O_5的含量。随着二元碱度从1.3提高至2.5,磷酸盐富集率增大,磷酸盐富集相nC2S-C3P中的P_2O_5含量呈现先迅速增大(B从1.3至1.7),然后逐渐减小(B从1.8至2.5)的趋势。当二元碱度和Al_2O_3质量分数分别控制在1.7和12%时,即当满足四元碱度R为1.23时,此八元钢渣体系有较好的磷酸盐富集效果,磷酸盐富集相nC_2S-C_3P内的P_2O_5的质量分数可以达到24.23%。     

1- and 3-hydroxylations, in addition to 4-hydroxylation, of debrisoquine are catalyzed by cytochrome P450 2D6 in humans

Twenty-one healthy Swedish Caucasian volunteers, representing different groups with 0-13 functional cytochrome P450 (CYP) 2D6 genes, were given a single oral dose of 20 mg of debrisoquine. The hypothesis of further oxidation of the main metabolite, (S)-4-hydroxydebrisoquine, in subjects with multiple CYP2D6 genes was tested by screening the 0-8-hr urine samples for dihydroxylated metabolites of debrisoquine with protonated molecular ions at m/z 208, using LC/MS. Three peaks were detected in a subject with 13 functional CYP2D6 genes. One compound was identified as dihydroxylated debrisoquine (presumably with hydroxylation at position 4 plus one of the positions in the aromatic ring). This metabolite had not been previously demonstrated in humans and was detected only in this subject. The other two compounds, which were measurable in various amounts in all subjects investigated, were identified as 2-(guanidinomethyl)phenylacetic acid and 2-(guanidinoethyl)benzoic acid. They had been previously detected in the urine of humans, dogs, and rats. They were distinguished by acid-catalyzed deuterium exchange of the hydrogens at the alpha-position, with respect to the carboxylic acid group, of the former but not the latter acid. The acids are formed by 3- and 1-hydroxylation of debrisoquine, respectively, followed by ring opening to aldehydes, which are further oxidized to acids. Strong Spearman rank correlations between debrisoquine products of 1- or 3-hydroxydebrisoquine and debrisoquine/4-hydroxydebrisoquine ratios (rS = 0.97 and rS = 0.96, respectively), using the intensity of the peaks of the reconstructed ion-current chromatograms, clearly showed that both hydroxylation steps are catalyzed by CYP2D6. Because reference compounds for the two acids were not available, the absolute quantities could not be determined.     

Fate of wheat bound malathion residues in rats during gestation

Malathion [S-1,2-di(ethoxycarbonyl) ethyl 0,0-dimethyl phosphorodithioate], treated wheat when stored for 28 months at 20 degrees C with or without food grade white mineral oil on grains contained about 62 and 79% of the applied insecticide as bound residues, respectively. These bound residues were present mainly in the form of the parent compound. The stored wheat containing bound malathion residues, as well as wheat material freshly spiked with malathion were fed to rats during gestation. No residues of malathion and/or metabolites were detected in urine, feces and body tissues. Further no significant effect on body weight, serum chemistry and cytochrome P450 levels were observed in the mothers. There was no evidence for the histopathological alteration or teratogenic anomalies in the fetuses. However, placental transfer of malathion was indicated by the presence of the insecticide residues in fetuses from rats fed wheat material containing bound residues.     

Luminescence and Energy Transfer Properties of Ca2Gd8(SiO4)6O2∶ A (A=Pb2+,Tm3+)Phosphors

Ca2Gd8(SiO4)6O2∶ A(A=Pb2 , Tm3 )phosphors were prepared through the sol-gel process. X-ray diffraction(XRD), scanning electron microscopy(SEM)and photoluminescence spectra were used to characterize the resulting phosphors. The results of XRD indicate that the phosphors crystallized completely at 1000 ℃. SEM study reveals that the average grain size is 300～1000 nm. In Ca2Gd8(SiO4)6O2∶ Tm3 phosphors, the Tm3 shows its characteristic blue emission at 456 nm(1D2-3F4)upon excitation into its 3H6 - 1D2(361 nm), with an optimum doping concentration of 1mol% of Gd3 in the host lattices. In Ca2Gd8(SiO4)6O2∶ Pb2 , Tm3 phosphors, excitation into the Pb2 at 266 nm(1S0-3P1)yields the emissions of Gd3 at 311 nm(6P-8S)and Tm3 at 367 nm(1D2 -3H6)and 456 nm(1D2-3F4), indicating that energy transfer processes of Pb2 - Gd3 and Pb2 - Tm3 have occurred in the host lattices.     

Synthesis, Characterization and Inhibition Effects of Vanadium Substituted Dawson-type Heteropoly Acids(Mo, P)

Four new vanadium substituted Dawson-type heteropoly acids H<,7>[P<,2>Mo<,17>VO<,62>]·39H<,2>O(1), H8[P2Mo16V2O62]·41H2O(2) H9[P2Mo15V3o62]·51H2O(3)and H8[P2Mo14V4O62H2]·45H2O(4)were prepared respectively. Their structures were determined by IR and ICE. The inhibition effects of vanadium substituted Dawson-type heteropoly acids(Mo, P) on free radical polymerization of methyl methacrylate(MMA) were investigated by dilato- metry. The results show that the rate of the polymerization of MMA decreases and the inhibition effects of the four heteropoly acids reach the inhibitor performance of hydroquinone at a certain ratio.     

NdFeB废料回收Nd2O3工艺试验及实践

较系统地研究了ＮｄＦｅＢ废料回收Ｎｄ２Ｏ３的工艺试验,并进行了工业生产,产品纯度高（Ｎｄ２Ｏ３≥９９％,Ｄｙ２Ｏ３≥９９％）,非稀土杂质低（ＳｉＯ２、ＣａＯ、Ｆｅ２Ｏ３均≤００５％）。产品可作为生产金属钕的原料,满足ＮｄＦｅＢ生产的要求,该工艺流程短,操作简便,且回收率高（ＮｄＯ３实收率＞８２％）,工业生产投资少,见效快,环境污染小等优点     

The metabolism of the hypolipidaemic drug sultosilic acid in rat, dog and man

1. Single oral doses of the hypolipidaemic drug [35S]sultosilic acid to rats (40 mg/kg), dogs (40 mg/kg) and man (7 mg/kg) were well absorbed. During three days, means of 59.2%, 58.8% and 61.8% in urine and 37.7%, 31.9% and 19.7% in faeces, were excreted by these species respectively. Most of the dose was excreted during the first 24 h. 2. Peak plasma levels of 35S were generally reached during 1-2 h after oral doses in rats (12 micrograms equiv./ml), dogs (45 micrograms equiv./ml) and two human subjects (15.2 and 10.3 micrograms equiv./ml). In humans, peak plasma levels of unchanged drug (at 1-1.5 h) were 10.5 and 6.3 micrograms/ml. Plasma concentrations of 35S increased almost proportionately to dose in rats following oral doses of 400 and 1200 mg/kg, although in dogs, concentrations were similar at these two dose levels but several times higher than at 40 mg/kg. 3. Tissue concn. of 35S were generally higher in rats than in dogs. Highest concn. occurred at 3 h in rats and 1 h in dogs. Apart from those in the liver and kidneys, tissue concn. were appreciably lower than the corresponding plasma levels. 4. The major radioactive component in dog urine was sultosilic acid. Rat and human urine contained sultosilic acid and also two more polar major metabolites. In male and female rat urine, the proportions of these excretory products differed and the proportions in male rat urine were similar to those in human urine. Sultosilic acid was also the only component detected in dog plasma, whereas rat and human plasma also contained the two urine metabolites. Dog bile contained a conjugate of sultosilic acid. 5. The two metabolites have been identified by mass spectrometry and nuclear magnetic resonance spectroscopy as products resulting from oxidation of the methyl in the p-toluenesulphonyl group. The structures assigned are the corresponding carboxylic acid and the hydroxymethyl derivatives.     

Determination of amino acids in biological fluids by capillary gas chromatography with nitrogen-phosphorus selective detection

A selective and sensitive method for the determination of protein and non-protein amino acids in biological fluids by capillary gas chromatography (GC) has been developed. The amino acids in the samples were directly converted into their N(O,S)-isobutoxycarbonyl methyl ester derivatives and measured by GC with nitrogen-phosphorus selective detection (NPD) using a DB-17ht capillary column. Using this method, the derivatives of the 21 protein amino acids and the 25 non-protein amino acids provided excellent NPD responses and were quantitatively and reproducibly resolved within 28 min. The lower detection limits of these amino acids, at a signal-to-noise ratio of 3, were ca. 6-150 pg injected. The calibration curves for each amino acid in the range of 0.02-2 micrograms were linear and sufficiently reproducible for quantitative analysis. This method was successfully applied to small urine and serum samples without prior clean-up; there was no evidence of interference from coexisting substances. Overall recoveries of amino acids added to urine and serum samples were 83-112%. The intra-assay and inter-assay R.S.D. of amino acids in these samples were 0.3-8.9% (n = 3) and 1.9-15.8% (n = 3), respectively.     

高铁铝土矿直接还原回收粒铁和氧化铝

 采用煤基直接还原熔分技术和氧化铝溶出的方法,研究了直接还原工艺对粒铁尺寸和粒铁收得率的影响,以及钙铝比[(w(CaO)/w(Al2O3))] 对渣相组成和渣中氧化铝的溶出影响。结果表明,当[(w(CaO)/w(Al2O3))]为1.7、[w(C)/w(O)]为1.4、还原熔分温度为1 450 ℃,还原熔分时间为20 min时,还原熔分过程中的粒铁尺寸最大,粒铁收得率也最高,粒铁尺寸和收得率分别为11.5 mm和93%。当[(w(CaO)/w(Al2O3))]为1.0时,渣相组成主要以钙铝黄长石(Ca2Al(Al,Si)2O7)为主,当[(w(CaO)/w(Al2O3))]为1.5时,渣相组成主要以钙铝黄长石(Ca2Al(Al,Si)2O7)、硅酸二钙(Ca2SiO4)和七铝十二钙(Ca12Al14O33)为主,当[(w(CaO)/w(Al2O3))]为1.7～1.9时,渣相组成主要以七铝十二钙(Ca12Al14O33)和硅酸二钙(Ca2SiO4)为主。当[(w(CaO)/w(Al2O3))]为1.7时,溶出时间为2.0 h时,氧化铝的溶出率最高,溶出率为87.5%,溶出率较0.5 h时提高了9.4%。因此,当渣系组成以七铝十二钙(Ca12Al14O33)和硅酸二钙(Ca2SiO4)为主时,更有利于氧化铝的溶出。     

Formation of methylated and phosphorylated metabolites during the fermentation process of verdamicin

In an attempt to understand the biosynthetic processes leading to the formation of verdamicin (end product), we have examined the patterns of the formation of methylated and phosphorylated metabolites, which resulted from either the addition of l-[methyl-(14)C]methionine or [(32)P]KH(2)PO(4) to the fermentation. Incorporation of label from l-[methyl-(14)C]methionine into the bioactive sisomicin, verdamicin, and the chromatographically polar components increased with the progression of time. Two methylated bioinactive metabolites were found in the culture broth after removal of the methylated bioactive metabolites. In contrast to the bioactive metabolites, incorporation of the methyl-(14)C label into the two methylated bioinactive metabolites decreased with the progression of time. A phosphorylated bioinactive metabolite (nonmethylated) was also found in the culture broth, fermented in the presence of [(32)P]KH(2)PO(4). The role of the phosphorylated metabolite in the biosynthesis of the bioactive metabolites cannot yet be explained.     

Epidemiological evaluation of Serratia marcescens clinical isolates in a general hospital during the past three years: appearance of O-antigens O2 and O14

One hundred sixteen isolates of Serratia marcescens collected in Showa University Fujigaoka Hospital between April in 1994 and March in 1997 were investigated by O-serotyping, biotyping and antimicrobial susceptibility testing. The results were as follows. 1. Of the total isolates, 37.1 and 24.1% were O2 and O14, respectively, and these values were higher than that of any other serotype. 2. In the hospital, the O2 strains were often isolates in the wards of neurology, plastic surgery, general surgery and ophthalmology, while the O14 strains were often isolated in the wards of urology and orthopedic surgery. 3. The isolation percentages of the biotypes 5307721 and 70405356 with PII 20E and Microscan systems were 81.1 and 50%, respectively. Both biotypes showed typical S. marcescens. There was no relation between O2 or O14 and biotypes. 4. All of the O2 isolates were susceptible to third generation cephems, cefotaxime, ceftazidime and cefpirome, and at least 88% were susceptible to aminoglycosides, whereas the O14 isolates were much more resistant to these antibiotics than the O2 isolates. 5. The isolation percentages of O2 and O14 from urine were 57.1 and 16.3%, whereas those from sputum and pharynx swab were 7.1 and 53.5%, respectively. 6. The isolation percentage of O14 susceptible to gentamicin was very high (96.5%), compared with that of between April in 1991 and March in 1994 (23.3%). Furthermore, increased isolation percentages of the O14 isolates susceptible to gentamicin, tobramycin and amikacin in this period were linked with the decrease in the annual purchased amount of each aminoglycoside and with the decreased isolation percentage from urine. These findings revealed the environments in which the O2 and O14 isolates in this period were predominant over other O-serotypes, while S. marcescens mediated by patients inhabits in the hospital.     

The effect of dimethoate selection on trichlorfon and dimethoate sensitivity in Musca domestica

Selecting of strain a Musca domestica resistant to trichlorphon with Bi 58 (active ingredient: dimethoate) resulted in an only slight (1.33-fold) increase of the resistance to dimethoate between 1974 and 1975. In the same time the resistance to trichlorphon rose to 5.28 times the original degree. The resistance extends to some other organophosphates, especially malathion, dichlorvos and bromophos, but not to diazinon. Among the insecticides registered for control of flies in pig-sties Bi 58 has the greatest chance, though there exists neither a certainty for the decrease of the resistance to trichlorphon nor for the non-appearance of a resistance to dimethoate. To overcome the problem of flies in stables and sties, particularly in plants of industrial cattle-breeding, complex measures must be taken.     

Preliminary results of treatment of solid tumors in children with non-standard radiotherapy]

Urinary excretion of mefenamic acid (MA) and its two oxidative metabolites, M-I (3'-hydroxymethyl derivative) and M-II (3'-carboxyl derivative), and their glucuronides was investigated in preterm infants undergoing MA therapy. MA was given orally at a dose of 2 mg/kg and the dose was repeated every 24 h a maximum of three times. Urine was collected for up to 5 d after the last dose, and MA and the metabolites were determined by a newly developed HPLC. The cumulative amounts of MA and the metabolites excreted in the urine varied from 7 to 46% of the total dose administered, and were less than those reported in adults and children. Significant correlation was observed between the plasma half-life of MA and the cumulative amount of MA and the metabolites excreted in the urine. These results suggest that long plasma half-lives of MA observed in preterm infants are due mainly to low activity of drug metabolizing enzyme(s). In an infant who received the two regimens of MA therapy about 2 weeks apart, the plasma half-life of MA was shortened and the urinary excretion of the MA metabolites including their glucuronides was greatly increased during this period. It is suggested that the activities of both cytochrome P-450(s) and glucuronyltransferase(s) related to MA metabolism rapidly increased during the first month of the infant's life.     

Reaction of O6-benzylguanine-resistant mutants of human O6-alkylguanine-DNA alkyltransferase with O6-benzylguanine in oligodeoxyribonucleotides

Inactivation of the human DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT), by O6-benzylguanine renders tumor cells susceptible to killing by alkylating agents. AGT mutants resistant to O6-benzylguanine can be made by converting Pro140 to an alanine (P140A) or Gly156 to an alanine (G156A). These mutations had a much smaller effect on the reaction with O6-benzylguanine when it was incorporated into a short single-stranded oligodeoxyribonucleotide. Such oligodeoxyribonucleotides could form the basis for the design of improved AGT inhibitors. AGT and mutants P140A and G156A preferentially reacted with O6-benzylguanine when incubated with a mixture of two 16-mer oligodeoxyribonucleotides, one containing O6-benzylguanine and the other, O6-methylguanine. When the 6 amino acids located in positions 159-164 in AGT were replaced by the equivalent sequence from the Escherichia coli Ada-C protein (mutant AGT/6ada) the preference for benzyl repair was eliminated. Further mutation incorporating the P140A change into AGT/6ada giving mutant P140A/6ada led to a protein that resembled Ada-C in preference for the repair of methyl groups, but P140A/6ada did not differ from P140A in reaction with the free base O6-benzylguanine. Changes in the AGT active site pocket can therefore affect the preference for repair of O6-benzyl or -methyl groups when present in an oligodeoxyribonucleotide without altering the reaction with free O6-benzylguanine.     

Sphingosine 1-phosphate stimulates hydrogen peroxide generation through activation of phospholipase C-Ca2+ system in FRTL-5 thyroid cells: possible involvement of guanosine triphosphate-binding proteins in the lipid signaling

Exogenous sphingosine 1-phosphate (S1P) stimulated hydrogen peroxide (H2O2) generation in association with an increase in intracellular Ca2+ concentration in FRTL-5 thyroid cells. S1P also induced inositol phosphate production, reflecting activation of phospholipase C (PLC) in the cells. These three S1P-induced events were inhibited partially by pertussis toxin (PTX) and markedly by U73122, a PLC inhibitor, and were conversely potentiated by N6-(L-2-phenylisopropyl)adenosine, an A1-adenosine receptor agonist. In FRTL-5 cell membranes, S1P also activated PLC in the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), but not in its absence. Guanosine 5'-O-(2-thiodiphosphate) inhibited the S1P-induced GTP gamma S-dependent activation of the enzyme. To characterize the signaling pathways, especially receptors and G proteins involved in the S1P-induced responses, cross-desensitization experiments were performed. Under the conditions where homologous desensitization occurred in S1P-, lysophosphatidic acid (LPA)-, and bradykinin-induced induction of Ca2+ mobilization, no detectable cross-desensitization of S1P and bradykinin was observed. This suggests that the primary action of S1P in its activation of the PLC-Ca2+ system was not the activation of G proteins common to S1P and bradykinin, but the activation of a putative S1P receptor. On the other hand, there was a significant cross-desensitization of S1P and LPA; however, a still significant response to S1P (50-80% of the response in the nontreated control cells) was observed depending on the lipid dose employed after a prior LPA challenge. S1P also inhibited cAMP accumulation in a PTX-sensitive manner. We conclude that S1P stimulates H2O2 generation through a PLC-Ca2+ system and also inhibits adenylyl cyclase in FRTL-5 thyroid cells. The S1P-induced responses may be mediated partly through a putative lipid receptor that is coupled to both PTX-sensitive and insensitive G proteins.     

Metabolism of tetramethrin isomers in rat: IV. Tissues responsible for formation of reduced and hydrated metabolites

1. To identify the sites of formation of the reduced metabolites, 3-hydroxy-cyclohexane-1,2-dicarboximide (3-OH-HPI-1 and -2), 1,2-cyclohexanedicarboxylic acid (TCDA) and 1-hydroxy-1,2-cyclohexanedicarboxylic acid (1-OH-HPA), in rat treated with 14C-labelled (1RS, trans)-tetramethrin, [3,4,5,6-tetrahydrophthalimidomethyl (1RS, trans)-chrysanthemate], bile-duct cannulated animals were orally or intravenously administered 14C-labelled 3,4,5,6-tetrahydrophthalimide (TPI) or 3,4,5,6-tetrahydrophthalic acid (THPA), precursors of these metabolites, and bile, urine and faeces were collected for analysis. 2. 3-OH-HPI-1 and 3-OH-HPI-2, which are cis-form reduced metabolites, and 1-OH-HPA were detected in bile and urine samples of the bile-cannulated rat treated intravenously and orally with 14C-labelled TPI, indicating their formation in tissues or blood. TCDA, a trans-form reduced metabolite, was not detected in bile, urine or faeces of the bile-cannulated rat treated intravenously with 14C-THPA, but was found in the faeces after oral application, indicating formation in the gastrointestinal tract. 3. To clarify whether 1-OH-HPA is produced from THPA via TCDA (hydroxylation via reduction) or by direct addition of H2O to its double bond (hydration), rats were orally administered 14C-labelled TCDA, and metabolites in urine and faeces were analysed. The observed lack of 1-OH-HPA indicated formation by direct addition of H2O to the double-bond of THPA. 4. To specify which tissues form reduced and hydrated metabolites, in vitro metabolism studies were carried out. Reduction to the cis-form was found to take place in blood cells, reduction to the trans-form took place in the gastrointestinal tract contents, and hydration took place in the liver and the intestinal tract contents.