Distribution and excretion of [14CH3S]methamidophos after intravenous administration of a toxic dose and the relationship with anticholinesterase activity

The tissue distribution and excretion of [¹⁴CH₃S]methamidophos was followed in female Sprague-Dawley rats after intravenous injection at a toxic, but nonlethal, dose (8 mg/kg). Radiolabel was rapidly distributed to all tissues at approximately equal concentrations. Peak tissue levels were achieved within 1–10 min except in the central and peripheral nervous system where peak levels (40 nmol/g) were found between 20 and 60 min, corresponding to peak signs of toxicity. Within 24 hr of dosing, 47% of the radioactivity was recovered in the urine and 34% as ¹⁴CO₂ with <5% in the feces over 7 days. Cholinesterase (ChE) inhibition was measured in erythrocytes, plasma, and various regions of the central nervous system (CNS) at selected times after administration of methamidophos at 8 mg/kg. The degree of acetylcholinesterase (AChE) inhibition in the three CNS regions was similar, reaching a minimum of 15–20% of control values at 30–60 min, when toxicity was most severe. The degree of erythrocyte AChE inhibition was less than that of the CNS although the time course was similar. Plasma ChE inhibition was more rapid than that of the CNS or erythrocytes and reactivation was slower. When similar concentrations of methamidophos to those found in vivo were incubated with CNS homogenates, plasma, or erythrocytes in vitro (5 × 10^?5M) a similar degree of inhibition occurred over the same time course. It is, therefore, concluded that the cholinergic toxicity produced by methamidophos is a result of the in vivo stability of this compound combined with its entry into the nervous system in sufficiently high concentrations to inhibit AChE.     

O,O,S-Trimethyl phosphorothioate effects on immunocompetence

O,O,S-Trimethyl phosphorothioate (OOS), a contaminant of technical formulations of some organophosphorus pesticides, was found to be immunotoxic at subtoxic doses in female C57Bl/6 mice. Mice treated orally with acute doses of 10 mg/kg OOS show no overt toxic signs such as weight loss or malaise. In addition, the levels of serum cholinesterase was not decreased. Histopathologic investigation demonstrated no alterations in liver, lung, kidney, heart, skin, brain, spleen, or gut. The LD₅₀ for delayed toxicity was approximately 35 mg/kg. Despite the lack of general toxic changes at doses of 5–10 mg/kg OOS, specific immunotoxic changes were found. The humoral or cell-mediated immune response of splenocytes from mice treated with 10 mg/kg OOS to in vivo immunization was diminished with respect to control animals. Responses were measured in ex vivo assays. Cytotoxic T-lymphocyte (CTL) responses were assessed by alloimmunization with the tumor P815 followed by a ⁵¹Cr release assay done ex vivo with splenic lymphocytes. Humoral responses were assessed by immunization with sheep red blood cells followed by a Jerne plaque assay to determine anti-sheep red blood cell antibody. Both cellular and humoral responses could be stimulated in vitro using cells from OOS-pretreated, primed animals, thus indicating that no permanent cellular elterations had occurred.     

Intestinal metabolism and absorption of carbaryl studied with a portal fistula

These data were obtained by use of a total and continuous portal vein fistula which virtually eliminated vascular redistribution of compounds absorbed from the gastrointestinal tract to nondigestive tissues (i.e., liver). The method allows direct measurement of the compounds absorbed, which is especially important in metabolism studies of ingested toxic compounds. These studies demonstrated that in vivo metabolism did occur within the intestine during the process of absorption of the pesticide carbaryl (naphthyl N-methylcarbamate) and naphthol, the hydrolysis product of the pesticide. Portal absorption of naphthol from a liquid diet (46 ± 4% of dose/120 min) was slower than from Ringer medium (75 ± 1%/120 min); portal absorption accounted for 82 ± 8 and 83 ± 4%, respectively, of the ¹⁴C absorbed from the intestine. The proportion of hydrophilic ¹⁴C-metabolites (water soluble) in portal blood varied from 6 to 89% and was a function of the substrate, dose vehicle (liquid diet vs Ringer), and time of portal fluid collection. Metabolism in the small intestine before absorption was confirmed for both substrates. The principal lipophilic constituent in portal fluid was the unmetabolized substrate for both carbaryl and naphthol; the principal ampholyte metabolite was naphthyl glucuronide. Although these in vivo data are qualitatively similar to evidence from previous in vitro studies, this in vivo evidence demonstrated that the extent of metabolism (and possibly detoxication) was considerably less than would be predicted from in vitro studies and indicates that the hazard of ingestion of carbaryl and other lipophilic toxic agents may be greater than realized.     

Correlation of blood and brain levels of the neurotoxic pyrethroid deltamethrin with the onset of symptoms in rats

Rats were injected intraperitoneally with ¹⁴C-labelled deltamethrin at the threshold doses required to produce the motor symptoms of toxicity of tremor and choreoathetosis. Blood and brain samples were analysed for their total radiolabel content, and were also extracted with ethyl acetate to determine the levels of extractable parent deltamethrin and 3-phenoxybenzyl-derived acid (the final radiolabelled metabolite after oxidative cleavage) and the residual radiolabel after this extraction. There was a clear correlation between symptom onset and blood and brain levels of deltamethrin. It was found that certain threshold levels of parent deltamethrin in the blood and brain were required for symptom development, and that the symptom persisted for as long as this threshold was maintained. The distribution of the radiolabel in various tissues was also followed over the time course of the blood and brain studies.     

Acetylcholinesterase of Aphis citricola: Properties and significance in determining toxicity of systemic organophosphorus and carbamate compounds

In apterous adults of the spirea aphid, Aphis citricola van der Goot, the optimum conditions for determining acetylcholinesterase (AChE) activity consist of reaction mixture of 0.1 M phosphate buffer (pH 7.5), 10^?3M acetylthiocholine (ASCh), and enzyme extract equivalent to 80 ± 3 μg protein incubated for 15 min at 30°C. The K_m value for ASCh (6.7 × 10^?5M) was much lower than that of butyrylthiocholine (BuSCh) (1.25 × 10^?2M). The enzyme activity was almost completely inhibited by 10^?6M paraoxon or 10^?5M eserine and was 84% inhibited by 10^?5M BW284C51 (a specific AChE inhibitor). DTNB was found to inhibit the enzyme activity and was therefore added at the end of the reaction. AChE activity of A. citricola was inhibited in vitro and in vivo by dimethoxon > dimethoate, and aldicarb sulfoxide > aldicarb > aldicarb sulfone. The in vivo effect correlates well with the toxicity level of the various toxicants. A neurotoxicity index which combines both mortality and in vivo inhibition of the aphid AChE activity is suggested as a measure for determining the toxicity of organophosphorus and carbamate compounds toward aphids.     

In vitro and in vivo effects of some pesticides on carbonic anhydrase enzyme from rainbow trout (Oncorhynchus mykiss) gills

Here we investigated the in vitro and in vivo effects of the pesticides, deltamethrin, diazinon, propoxur and cypermethrin, on the activity of rainbow trout (rt) gill carbonic anhydrase (CA). The enzyme was purified from rainbow trout gills using Sepharose 4B-aniline-sulfanilamide affinity chromatography method. The overall purification was approx. 214-fold. SDS-polyacrylamide gel electrophoresis showed a single band corresponding to a molecular weight of approx. 29 kDa. The four pesticides dose-dependently inhibited in vitro CA activity. IC₅₀ values for deltamethrin, diazinon, propoxur and cypermethrin were 0.137, 0.267, 0.420 and 0.460 μM, respectively. In vitro results showed that pesticides inhibit rtCA activity with rank order of deltamethrin > diazinon > propoxur > cypermethrin. Besides, in vivo studies of deltamethrin were performed on CA activity of rainbow trout gill. rtCA was significantly inhibited at three concentrations (0.25, 1.0 and 2.5 μg/L) at 24 and 48 h.     

The relationship between the pharmacokinetics of intravenous cismethrin and bioresmethrin and their mammalian toxicity

The distribution and excretion of [¹⁴C]alcohol-labeled cismethrin and bioresmethrin was determined after intravenous administration to rats. Initially the label distribution of both isomers was similar, but differences occurred at later times mainly due to the retention of 5-benzyl-3-furylcarboxylic acid, a metabolite of bioresmethrin, in high concentration in the blood. Retention of this metabolite accounted for the slower excretion of bioresmethrin label compared to cismethrin. After administration of either isomer, parent pyrethroid was rapidly cleared from the blood and liver, and both isomers rapidly entered the central nervous system reaching peak concentrations within 2–5 min. Brain cismethrin concentrations exceeding 3.5 nmol/g were associated only with animals showing tremors. These levels of cismethrin are maintained for up to 30 min but bioresmethrin was depleted more rapidly possibly due to brain metabolism. It is concluded that the low toxicity of bioresmethrin is possibly due to the inability of this isomer to interact with the site of action in the central nervous system and not, as previously suggested, primarily because of more rapid metabolism in the liver.     

The toxicological significance of paraoxon deethylation

The in vivo formation of deethylation and hydrolytic products of paraoxon degradation after parathion or paraoxon administration was nearly equal in control male rats, and the relative abundance of metabolites was not appreciably altered by pretreatment of rats with enzymeinducing agents. However, pretreatment with inducers dramatically increased the oxidative paraoxon O-deethylase of male rat liver while having little effect on hydrolytic enzymes. Prior to induction, the hepatic O-deethylase activity was greatly inferior to the various hydrolytic enzymes, but nearly equal levels of both enzyme systems were found after induction. These results indicate that a large portion of the hepatic hydrolases detected in vitro is not active in vivo. It also appears that the majority of the induced hepatic deethylase was not involved in vivo at the dosage levels employed. The in vivo metabolism of monoethyl paraoxon was also demonstrated. The predominant metabolite of ethyl-[1-¹⁴C]monoethyl paraoxon is ¹⁴CO₂, while phenyl-[1-¹⁴C]monoethyl paraoxon yielded 4-nitro[1-¹⁴C]phenol. Paraoxon deethylation was also shown to be an important detoxication mechanism in female rats and male mice and must be considered in interpreting the toxicological properties of parathion and paraoxon.     

Effect of hepatic enzyme inducers on the in vivo and in vitro metabolism of dicrotophos,dimethoate, and phosphamidon in mice

Daily 75 mg/kg phenobarbital ip injections for 3 days or 25 ppm dieldrin in the diet of mice for 14 days caused an increase in liver cytochrome P-450 and blood B-esterase. Liver A-esterase was not significantly increased. Under in vitro conditions, phenobarbital and dieldrin induced the oxidative as well as hydrolytic metabolism of dicrotophos, dimethoate, and phosphamidon by liver homogenates or combined microsomes plus 105,000g supernatant fractions. The concentration of dimethoxon was increased more than fourfold by the pretreatments after incubation for 4 hr at 37.5°C with NADPH added. The organophosphorus insecticides used in this study were not metabolized as well by the liver microsomes alone or 105,000g supernatant alone, as by the combination of microsomes and 105,000g supernatant. Under in vivo conditions in mice, phenobarbital and dieldrin treatments increased the urinary recovery of metabolites in the initial 6 hr after [¹⁴C]carbonyl-dimethoate or [¹⁴C]N-ethyl-phosphamidon administration. Analysis of urine showed that the inducers caused a more than sixfold increase in dimethoxon recovered and twofold increase in water-soluble nontoxic metabolites within 6 hr after dimethoate administration. With phosphamidon both inducers increased the rate of metabolism, and the total recovery in aqueous and chloroform fractions was decreased. These results suggest that increased dimethoate toxicity after phenobarbital and dieldrin treatments in whole animals results from stimulation of the activation of dimethoate to dimethoxon, while the increase in hydrolytic products after both pretreatments results in decreased toxicity of the direct acetylcholinesterase inhibitors, dicrotophos and phosphamidon.     

Risk assessment of pesticides and fungicides for acid-base regulation and salt transport in rainbow trout tissues

Carbonic anhydrase enzymes have been shown to play an important role in ion transport and pH regulation in several organisms including fish. Despite this information and the wealth of knowledge regarding the significance of CA enzymes in fish, few studies have reported the hazardous effects of chemicals on fish CA. Using rainbow trout (Oncorhynchus mykiss) as a model, this study aimed to determine the risk of pesticides and fungicides on fish carbonic anhydrase enzymes. For this purpose, screening of rainbow trout carbonic anhydrase activities was carried out in the presence of some pesticides and fungicides. Carbonic anhydrase enzymes were initially purified from rainbow trout liver, muscle, kidney and brain, and exposed to pesticides and fungicides, including mancozeb, cypermethrin, deltamethrin and dinocap. Pesticides and fungicides dose-dependently decreased in vitro CA activity at micromolar concentrations. Since deltamethrin was the most powerful inhibitor for all tissues in in vitro experiments, it was chosen for in vivo analysis as well. rtCAs were significantly inhibited by the three concentrations of deltamethrin (0.25, 1.0 and 2.5 μg/L) at 24th and 48th hours. Our findings indicate that deltamethrin, dinocap, mancozeb and cypermethrin are potent inhibitors for fish CA enzymes, and might cause undesirable results by disrupting acid-base regulation as well as salt transport in freshwater or seawater adapted fish.     

Herbicidal interference with the photochemical activities of chloroplasts (in vivo and in vitro) of certain crop and weed species

The independent modes of action of diuron and atrazine on the photochemical activities of chloroplasts (In vivo and in vitro) from the leaves of crop plants Pisum sativum and Pennisetum typhoides and the weeds Amaranthus viridis and Cyperus rotundus were investigated. Hill reaction activity (DCPIP photoreduction) of in vivo chloroplasts (chloroplasts isolated from herbicide-sprayed plants) was unaffected by treatment at sublethal or intermediate levels of diuron or atrazine while that of in vitro chloroplasts (chloroplasts incubated in the required herbicidal concentration) was severely inhibited. The ferricyanide catalyzed noncyclic photophosphorylation was markedly reduced in both the in vivo and in vitro chloroplast systems. N-Methyl phenozonium sulfate (PMS)-mediated cyclic photophosphorylation was inhibited in the in vivo system while a pronounced enhancement of activity was noticed in the in vitro chloroplasts. The rate of NADP⁺ photoreduction was severely inhibited in the in vitro chloroplasts. The unaffected in the in vivo system. The herbicidal effects on the photoreactions of isolated chloroplasts were compared with chloroplasts isolated from herbicide-sprayed plants.     

In vitro and in vivo effects of some pesticides on glucose-6-phosphate dehydrogenase enzyme activity from rainbow trout (Oncorhynchus mykiss) erythrocytes

We investigated the in vitro and in vivo effects of some pesticides on rainbow trout erythrocyte glucose-6-phosphate dehydrogenase enzyme. The enzyme was purified 1691-fold with a specific activity of 16.235 U/mg protein and a yield of 63%. Cypermethrin, and propoxur inhibited glucose-6-phosphate dehydrogenase enzyme in vitro and deltamethrin inhibited both in vivo and in vitro. The obtained IC₅₀ values for deltamethrin, cypermethrin, and propoxur were 0.63, 1.02, and 12 mM, respectively. The activity of the control was determined as 5.17 ± 0.62 U/g Hb in in vivo studies. The enzyme activities of the groups treated with 0.25 g/L deltamethrin were measured at 6, 12, 24, 48, and 72 h, and found to be 4.32 ± 0.47, 3.57 ± 0.39, 3.47 ± 0.45, 2.86 ± 0.37, and 2.31 ± 0.32 U/g Hb. In vivo experiments showed that deltamethrin significantly inhibited the G6PD enzyme activity after the 48th h (p < 0.05).     

The biochemical basis of resistance to organophosphorus insecticides in the sheep blowfly, Lucilia cuprina

The metabolism in vivo and in vitro of [¹⁴C]parathion and [¹⁴C]paraoxon was studied in a susceptible (LS) and an organophosphorus-resistant (Q) strain of the sheep blowfly, Lucilia cuprina. Both strains detoxified the insecticides in vivo via a number of pathways, but the resistant strain produced more of the metabolites diethyl phosphate and diethyl phosphorothionate. No difference was found between strains in the rate of penetration of the compounds used. Also, in vitro studies showed no difference between strains in the sensitivity of head acetylcholinesterase to inhibition by paraoxon. Both the microsomal and the 100,000g supernatant fractions degraded paraoxon, but resistance in Q could be explained by the eightfold greater rate of diethyl phosphate production with or without added NADPH. Parathion was also degraded to diethyl phosphorothionate by an NADPH-requiring enzyme in microsomal preparations from both strains. However, Q produced significantly more diethyl phosphorothionate in vivo than LS. It was concluded that organophosphorus resistance in Q was due mainly to a microsomal phosphatase hydrolyzing phosphate but not phosphorothionate esters, probably enhanced by a microsomal oxidase detoxifying the latter.     

Penetration of insecticides through the foregut of the honeybee (Apis mellifera L.)

The rates of penetration of ¹⁴C-labeled insecticides (parathion, carbaryl, and dieldrin) through the foregut of the honeybee (Apis mellifera L.) were measured in vitro and in vivo. Uptake of the insecticides from the lumen of the foregut into foregut tissue was directly proportional to insecticide lipophilicity, but penetration through the foregut was not. Of the three insecticides studied, parathion appeared to possess the optimal physicochemical characteristics required for penetration. The uptake of carbaryl and release of dieldrin by the foregut tissues may limit their respective penetration rates. Insecticide penetration was found to be inversely proportional to the sucrose concentration in the lumen of the foregut in both in vitro and in vivo studies. The oral toxicity of carbaryl showed a similar dependence on the sucrose concentration of the solution in which the insecticide was fed. The data presented indicate that the honeybee foregut is permeable to lipophilic compounds and strongly suggest that this permeability may contribute substantially to the toxicity of orally ingested insecticides in this insect.     

Comparative effects of lindane and deltamethrin on mortality, growth, and cellulase activity in earthworms (Eisenia fetida)

Laboratory tests were conducted to compare the effects of various concentrations of lindane and deltamethrin on mature earthworms (Eisenia fetida) cultured in artificial soil during typical acute (14d) and subchronic (42d) exposure periods. The effects of the two pesticides on earthworm mortality, growth inhibition, and cellulase activity were determined for different exposure durations. The toxicity order for earthworm mortality from the 14-day exposure was lindane > deltamethrin, with median lethal concentrations (LC₅₀) of 162.1 and 432.9 mg kg⁻¹, respectively. Earthworms exposed to deltamethrin showed dose-dependent toxic effects on growth and cellulase activity only from the acute exposures, whereas lindane’s effects on these activities were seen correlated with both the acute and subchronic doses. Also, changes in biomass and cellulase activity during the subchronic exposure period appear to be a more sensitive parameter than the LC₅₀ value in assessing pesticidal injury.     

Metabolism of O,O,S-trimethyl phosphorothioate in rats after oral administration of a toxic dose,and the effect of coadministration of its antagonistic thionate isomer

The in vivo metabolism of [¹⁴CH₃S]- and [¹⁴CH₃O]O,O,S-trimethyl phosphorothioate (OOS) was followed in rats after oral administration of threshold or LD₅₀ toxic doses of 20 or 60 mg/kg. Similar metabolic studies were conducted with coadministration of 1% O,O,O-trimethyl phosphorothionate (OOO), which prevented all signs of delayed toxicity, including weight loss. When administered alone, OOS was metabolized mainly (50–60%) via removal of the CH₃S moiety, which was largely converted to expired CO₂. Approximately 20% of the compound was O-demethylated, presumably by conjugation with glutathione, and then further metabolized to CO₂. Major urinary products were identified as O,O-dimethyl phosphoric acid (50–60%) and O,S-dimethyl phosphorothioic acid (～20%). Coadministration of OOO caused a slight decrease (～5%) in the cleavage of the CH₃S moiety, indicated by a reduction in ¹⁴CO₂ from [¹⁴CH₃S]OOS and a quantitatively similar increase in the formation of O,S-dimethyl phosphoric acid. Limited pharmacokinetic studies indicated that OOS was rapidly absorbed and distributed throughout the body. Coadministration of 1% OOO caused a slight increase in the blood half-life of parent OOS when administered at 60 mg/kg. It was concluded that a small proportion of the cleavage of the CH₃S moiety from OOS is involved in the intoxication process, and that this intoxication reaction is specifically inhibited by OOO.     

The apparent in vivo neuromuscular effects of the δ-endotoxin of Bacillus thuringiensis var. israelensis in mice and insects of four orders

Alkaline-dissolved crystal δ-endotoxin from Bacillus thuringiensis var. israelensis (serovar H 14) was injected into mice and seven species of insects representing the orders Lepidoptera, Orthoptera, Coleoptera, Hemiptera, and Diptera. High in vivo toxicity, at 1 to 5 ppm (μg toxin/g body wet wt), was observed with mice and some insects, including some that are not sensitive to the toxin when administered orally. Neuromuscular effects were observed when the toxin was injected directly into the body cavity of the test animals. Biochemical studies suggested that different protein fragments within the crystal δ-endotoxin may be responsible for the majority of the mosquito larvacidal activity and the neurotoxic symptoms observed in larvae of Trichoplusia ni.     

The effect of pretreatment with S,S,S-tributyl phosphorotrithioate on deltamethrin resistance and carboxylesterase activity in Aphis gossypii (Glover) (Homoptera: Aphididae)

The synergism of S,S,S-tributyl phosphorotrithioate (DEF) and its effect on carboxylesterase activity were investigated in deltamethrin-selected resistant (DRR) and susceptible (DSS) strains of cotton aphids, Aphis gossypii (Glover). Compared to the DSS strain, the DRR strain showed 23,900-fold resistance to deltamethrin, and 7560- and 99-fold cross-resistance to bifenthrin and ethofenprox, respectively. The synergist, DEF, increased the toxicity of both deltamethrin and bifenthrin, but not of ethofenprox when DEF was pretreated of 15 h. DEF exhibited significant inhibition on the carboxylesterase activity in the DRR strain, but no significant effect on that of the DSS strain in vitro. After the cotton aphids exposing to DEF, the carboxylesterase activity decreased gradually until 15 h and then gradually recovered until 24 h in the DRR strain, which fluctuated according to the effect of DEF on the deltamethrin toxicity detected using DEF pretreatment in the DRR strain. Therefore, our studies suggested that the effect of DEF on carboxylesterase was associated with deltamethrin resistance in the DRR strain.     

The metabolism of 1-naphthyl methylcarbamate by Periplaneta americana

The in vivo release of ¹⁴CO2 arising from decarbamoylation of l-naphthyl methyl [¹⁴C]carbamate (carbaryl) injected into male and female Periplaneta americana was measured over the range from 0.2 to 50 nmol carbaryl/g body weight. The amount of ¹⁴CO2 released was proportional to the dose of [¹⁴C]-carbaryl injected and was not significantly different between male and female cockroaches. Carbaryl was found to be more toxic to male (KD100, 12 nmol carbaryl/g) than female (KD100′ 57 nmol carbaryl/g) cockroaches, at any dose which caused knockdown, females showed a greater ability to recover from the toxic syndrome than did males. The [¹⁴C]-carbaryl metabolism (decarbamoylation) was temperature dependent and could be partially inhibited by sesamex, tri-orthocresyl phosphate and anoxia. Secondary effects of carbaryl poisoning were severe dehydration of the animals and in some cases abdominal swelling due to air being gulped into the crop. The amount of dehydration was essentially unaltered by the chemical inhibitors, but was partially reduced by anoxia and cooling. In the most severe cases of dehydration animals lost 18 % of their body water content.     

Toxico‐kinetics,recovery efficiency and microsomal changes following administration of deltamethrin to black Bengal goats

A study of the toxico‐kinetics, recovery percentage from different substrates, cytotoxicity and role of cytochrome P₄₅₀ and b₅ of liver microsome in the metabolism of deltamethrin were carried out in female black Bengal goat. The ALD₅₀ value of deltamethrin in goat by intravenous route lies between 0.2 and 0.6 mg kg^?1. Intravenous disposition kinetics using a dose of 0.2 mg kg^?1 showed that the maximum blood concentration of deltamethrin was recorded at 0.5 min, followed by rapid decline, and a minimum concentration was detected at 6 min after administration. The following values were obtained : Vd_area 0.148 (± 0.02) litre kg^?1; t_1/2 (α) 0.22 (± 0.02) min; t_1/2 (β) 2.17 (± 0.37) min; K_el 1.05 (± 0.24) min^?1; AUC 4.30(± 0.45) µg min ml^?1; Cl_B 0.05 (± 0.006) litre kg^?1 min^?1; T～B 1.93 (± 0.58); fc 0.40(± 0.05). After 10 min, liver retained the maximum residue, and heart, adrenal gland, kidney, spleen, fat and brain also held the insecticide; liver, fat, heart and spleen retained residue after 30 min, and bone, liver and fat retained residue after 60 min of intravenous administration. Oral absorption of deltamethrin was poor and inconsistent, and approximately 65% of administered dose was recovered from faeces and gastrointestinal contents. The excretion of deltamethrin through urine was meagre, and only 0.01 and 0.013% of the administered dose was recovered after 3 and 5 days of oral administration respectively. All the tissues retained the residue after 3 days; while fat, rumen, reticulum, omasum, abomasum, large and small intestine and bone retained the residue after 5 days of oral administration; and the percentage recoveries were 1.73 and 0.027 respectively. Deltamethrin reduced the level of cytochrome P₄₅₀ content of liver microsomal pellet of goat after 5 days of oral administration. Histopathological examination of liver, kidney, heart, spleen brain and lung sections of treated goats did not reveal any pathological changes. © 2001 Society of Chemical Industry