M. Humayoun Akhtar

Comparative metabolism of deltamethrin and 3-phenoxybenzoic acid in chickens.

A comparative metabolism of [benzyl 14C]deltamethrin and 3-phenoxybenzoic acid (3-PBacid) was carried out in chickens. The effect of oral and intravenous route of administration was also investigated. There was no difference in the metabolic profile of [14C] portion of deltamethrin and 3-PBacid. Similarly, no effect on the nature of metabolites excreted due to mode of administration was observed. Biotransformation of orally dosed compounds did not occur in the intestine, but were absorbed and metabolized by liver (deltamethrin) and kidney (3-PBacid). 3-PBacid, the primary metabolite of deltamethrin, was readily metabolized into 3-hydroxy benzoic acid (3-HO-Bacid) which is conjugated with a variety of endogenous substances to form sulphates, glucuronides, butyl ester and peptides. HPLC and LC-Ms methods were used to ascertain the structures of metabolites.

Deltamethrin residues in milk and tissues of lactating dairy cows

Lactating dairy cows were fed deltamethrin (2 or 10 mg kg-1 feed) for 28 consecutive days and deltamethrin residues measured in milk and tissues. Deltamethrin residues were higher relative to dose administered. The order of relative concentrations of deltamethrin in tissues, measured 1, 4, and 9 days after the last dose was: renal fat greater than subcutaneous fat greater than forequarter muscle greater than hindquarter muscle greater than liver greater than kidney. Depletion of deltamethrin residues in milk was very rapid indicating the half-life of the insectide of about 1 day. Trace amounts of deltamethrin metabolites 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (less than 0.0235 ppm) and 3-phenoxybenzoic acid (less than 0.034 ppm) were also detected in milk and tissues of treated cows.

Fate and residues of 14C-chloramphenicol in laying chickens

Studies were conducted to determine the metabolic fate of chloramphenicol (CAP) in White Leghorn using the 14C-labelled compound. In one experiment birds were administered orally via intra-crop, a single dose of 100 mg (equivalent to 66 mg kg-1 body weight) of CAP containing 14 microCi 14C-CAP, and its absorption, elimination and distribution in plasma were recorded. Orally dosed 14C-compound was rapidly absorbed, efficiently distributed in plasma and eliminated in excreta (> 70% in 5 hr). After 5 h, CAP equivalent residues in issues were lower than 15 micrograms g-1 for this treatment. In a second experiment birds were given intra-crop dose of either 0.5 or 5 mg of CAP (each dose contained 2.5 microCi 14C-CAP) daily for five consecutive days followed by a seven day withdrawal period and elimination of 14C in excreta and eggs was monitored. More than 95% of the administered 14C was eliminated within the first 24 h after dosing. Radiocarbon (14C) was deposited preferentially in yolks compared to albumen or other tissues. Residues declined when feeding was stopped. Various metabolites were isolated and identified by a combination of TLC, LC, and LC-MS. The main metabolic route of CAP in laying hens appears to be the glucuronidation. Cleavage of the dichloroacetate moiety was only a minor route.

Bioavailability of bound 14C residues in rats from bean plants treated with 14C-deltamethrin

Abstract Bean plants were treated with deltamethrin labeled with 14 C at the methyl or benzylic position. The aerial portion of the plants was exhaustively extracted with solvents and the extracted material containing bound 14 C residues was fed to rats. After 4 days 60% and 53% of the dose was excreted in feces and 31% and 20% in the urine from rats fed extracted bean plants treated with deltamethrin labeled at the methyl and benzylic position, respectively. The data demonstrated that bound residues in bean plants treated with deltamethrin may be bioavailable in rats.

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.

Bioavailability of bound pesticide residues and potential toxicologic consequences

Conclusions The use of 14C-labeled pesticides has made us aware of the existence of bound residues in edible tissue and plants. These residues would escape detection by the conventional analytical methods and would result in an underestimation of the edible tissue or plant burden of total pesticide residues. The methodology for the analysis of bound pesticide residues is still in the developmental stage. The total 14C-bound residues in tissues and plants are usually estimated by combustion of the extracted material to yield 14CO2. The high temperature distillation technique and supercritical methanol may provide a possible means for the chemical identification of bound residues. However, the application of these techniques to bound residue analysis of other pesticides has not been fully explored. A major portion of bound pesticide residues in plant tissues may be associated with lignin. Thus, lignin formation in plants may serve as a system for plants to store pesticide residues by incorporating them into insoluble lignin. The feeding of plant materials containing 14C-bound residues to monogastric animals indicates that these residues may be considered to be of little toxicological concern. However, recent studies have shown that even lignin-bound pesticide residues can be bioavailable to a great extent and may possess ecotoxicological significance (12). The binding of pesticide residues in edible tissues of meat also appears to yield fractions of residues that are not readily bioavailable. This need not necessarily be equated with safety, as the minimal levels for toxicity are not known. In addition, these small amounts of pesticide could be cumulative and toxic over time. Whether bound pesticide residues are of any environmental significance will remain a matter of conjecture until more data are available. However, judging from the limited available information. it appears that bound residues may not present any problem as long as such residues do not accumulate in significant amounts. It is recommended that more coordinated research be undertaken for a better assessment of this complex problem.

Reaction of diazomethane with chlorothalonil

Abstract The reaction between diazomethane and chlorothalonil produced a major compound identified as 4-methoxy-2,5,6-trichloroisophthalonitrile. The latter compound was also produced by methylating the 4-hydroxy derivative of chlorothalonil with diazomethane. It is suggested that derivatization of the hydroxy metabolite of chlorothalonil in presence of the parent compound will produce a single common derivative resulting in erroneous residue data.

Sequential participation of glutathione and sulph‐hydryl (S) in reductive dechlorination of 2, 4‐di‐, and 2, 4, 5‐trichloro phenacyl chlorides by soluble fraction (105,000 x g) of chicken liver homogenate.

The mode of reductive dechlorination of alpha-chloroacetophenones, 2,4-di-, and 2,4,5-trichloro phenacyl chlorides into respective acetophenone by soluble fraction (105,000 x g) from chicken liver homogenate has been investigated. The transformation involved the sequential participation of glutathione and a sulph-hydryl. The phenacyl chloride first reacted with glutathione to yield the phenacyl glutathione, which in turn, in the presence of a sulph-hydryl, was reduced enzymatically to produce the ketone, probably via a disulfide intermediate.

Bioavailability in rats of bound residues present in liver and intestine of chickens fed diet treated with 3-phenoxybenzoic acid

Abstract The bioavailability of bound residues generated after exhaustive extraction with methanol from liver and intestine of chickens fed diet treated with 3-phenoxybenzoic acid (3-PB acid) was investigated in rats. 3-PB acid was present in the form of bound residue in liver and intestine of chickens and did not undergo any detectable biotransformation after it was consumed by rats. After six days, 10.2% and 8.5% of the bound residues were eliminated in urine, while 78.7% and 81.6% were voided in feces from rats fed liver and intestine of chickens, respectively. However, about 30–45% of the total 14C in feces was readily extractable with methanol. No 14C residues were detected in liver, kidney, lungs and heart. The data shows that bound residues of 3-PB acid from liver and intestine of chickens are bioavailable to rats.

In vitro metabolism of deltamethrin by stem and leaf homogenates of tobacco plants

Abstract Stem and leaf homogenates from tobacco plants metabolised deltamethrin by oxidative and hydrolytic actions on the insecticide. Although a major portion of deltamethrin remained unchanged, metabolites such as 3-phenoxybenzaldehyde, 3-phenoxybenzoic acid and 3-(2,2-dibromonyl)-2,2-dimethylcyclopropanecarboxylic acid were formed. The data suggest a major portion of the insecticide would remain unchanged when absorbed by tobacco plants.