M.K. Srivastava

Azadirachtin, a neem biopesticide: subchronic toxicity assessment in rats.

Azadirachtin, a biopesticide obtained from neem, was subjected to subchronic toxicological testing to document its safety for use as a pesticide. Azadirachtin technical 12% orally administered to male and female rats at doses of 500, 1000 and 1500 mg/kg/day for 90 days did not produce any signs of toxicity, mortality, changes in tissue weight, pathology and serum and blood parameters. It can be suggested that azadirachtin at the highest dose tested is well tolerated by rats of both sexes. The highest dose, 1500 mg/kg, can be used as a basal dose for the determination of the no-observed-effect level (NOEL) of azadirachtin to calculate its safety margin.

Toxicological impact of technical imidacloprid on ovarian morphology, hormones and antioxidant enzymes in female rats

Technical imidacloprid was evaluated for its effect on ovarian morphology, hormones and antioxidant enzymes in female rats after 90 days oral exposure. Luteinizing hormone (LH), follicle stimulating hormone (FSH) and progesterone levels were estimated in serum of rats and activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and level of reduced glutathione (GSH) and lipid peroxidation (LPO) were estimated in ovary after oral administration of imidacloprid (5, 10, and 20mg/kg/day) for 90 days. Decreased ovarian weight together with significant patho-morphological changes in follicles, antral follicles and atretic follicles were observed at 20mg/kg/day. Imidacloprid at 5 and 10mg/kg/day has not produced any significant changes in ovarian morphology, hormones and antioxidant status of ovary. However 20mg/kg/day dose has produced significant alterations in the levels of LH, FSH and progesterone. Similarly significant changes in SOD, CAT, GPx, GSH, and LPO were observed at 20mg/kg/day dose level. Therefore, it is concluded that imidacloprid at 20mg/kg/day dose level has produced significant toxicological impact on ovary of female rats as evident by pathomorphological changes, hormonal imbalance and generating oxidative stress and can be considered primarily as Lowest Observed Effect Level (LOEL) for chronic study.

Studies on rat thyroid after oral administration of mancozeb: Morphological and biochemical evaluations

Mancozeb, an ethylenebisdithiocarbamate (EBDC), has been studied for its effects on rat thyroid. Single oral administration of mancozeb at different concentrations (9600, 12 000, 15 000 and 18 750 mg kg−1 body wt) has derived the oral LD50 value as 15 000 mg kg−1 body wt. in male rats. Mancozeb at repeated oral doses of 500, 1000 and 1500 mg kg−1 day−1 for periods of 30, 90, 180 and 360 days has produced dose‐dependent signs of toxicity and death of animals. The fungicide caused a significant increase in thyroid/body weight ratio and histopathological changes. Reduced levels of thyroid radioiodine (125I) uptake, serum protein‐bound iodine (PB125I), thyroxine (T4) and reduced activity of thyroid peroxidase (TPO) have also been observed after exposure to mancozeb. Thus, mancozeb has been shown to produce marked structural and functional changes in thyroid of rats.© 1997 John Wiley & Sons, Ltd.

Analysis of imidacloprid residues in fruits, vegetables, cereals, fruit juices, and baby foods, and daily intake estimation in and around Lucknow, India

A total of 250 samples-including fruits, fruit juices, and baby foods (50 samples each), vegetables (70 samples), and cereals (30 samples)-were collected from Lucknow, India, and analyzed for the presence of imidacloprid residues. The QuEChERS (quick, easy, cheap, effective, rugged, and safe) method of extraction coupled with high-performance liquid chromatographic analysis were carried out, and imidacloprid residues were qualitatively confirmed by liquid chromatography-mass spectrometry. Imidacloprid was not detected in samples of fruit juices and baby foods. It was, however, detected in 38 samples of fruits, vegetables, and cereals, which is about 15.20% of the total samples. Of samples of fruits, 22% showed the presence of imidacloprid, and 2% of samples showed residues above the maximal residue limit. Although imidacloprid was detected in 24% of vegetable samples, only 5.71% showed the presence of imidacloprid above the maximal residue limit. However, 33% of cereal samples showed the presence of imidacloprid, and about 3% of samples were above the maximal residue limit. The calculated estimated daily intake ranged between 0.004 and 0.131 µg/kg body weight, and the hazard indices ranged from 0.007 to 0.218 for these food commodities. It is therefore indicated that lifetime consumption of vegetables, fruits, fruit juices, baby foods, wheat, rice, and pulses may not pose a health hazard for the population of Lucknow because the hazard indices for imidacloprid residues were below one.

Disposition and acute toxicity of imidacloprid in female rats after single exposure.

Single dose of imidacloprid (IMI-20mg/kg bodyweight) was orally administered in female rats. Its disposition along with two metabolites 6-chloro nicotinic acid (6-CNA) and 6-hydroxy nicotinic acid (6-HNA) was monitored in organs (brain, liver, kidney, and ovary) and bodily fluids (blood, urine) at 6, 12, 24 and 48h and faeces at 24 and 48h. Maximum concentration (Cmax) of IMI and metabolites in each organ and bodily fluid occurred after 12h. Area under curve (AUC) of IMI ranged from 35 to 358μg/ml/h; 6-CNA: 27.12-1006.42μg/ml/h and 6-HNA: 14.98-302.74μg/ml/h in different organs and bodily fluids. Clearance rate of IMI was maximum in ovary followed by kidney, liver, brain, faeces, blood and urine. Percent inhibition of acetyl-cholinesterase (AChE) was comparable in brain and Red Blood Cells (RBC) at 6-48h which suggests the RBC-AChE as valid biomarker for assessing IMI exposure. It is evident that IMI was absorbed, metabolized, and excreted showing increased level of serum enzymes like Glutamic oxaloacetic transaminase (GOT), Glutamic pyruvic transaminase (GPT) and biochemical constituents like billirubin and Blood Urea Nitrogen (BUN) at 48h. These data suggest that IMI is widely distributed, metabolized and induced toxicology effects at 20mg/kg bodyweight to female rats.

Prenatal effects of technical hexachlorocyclohexane in mice

Technical hexachlorocyclohexane (5, 25, and 50 mg/kg/d) was orally administered to mice during the pre- and postimplantation period. While mice exposed to HCH during the preimplantation period did not show fetolethality, exposure during the postimplantation period showed dose-dependent effects on fetuses as evidenced by increase in percentage resorption, higher level of HCH residue, and decreased serum progesterone level. The absence of anomalies in fetal gross morphology and skeleton suggests technical HCH is nonteratogenic in mice.

Organochlorine insecticide residues in cattle feed

The role of organochlorine insecticides (OCIs) has been very vital in public health and agricultural production in developing countries including India. Despite the restricted use and/or banning of these compounds, several reports indicate that pollution with OCIs still exists, and may be of public and environmental health significance even in developed countries (Kim 1984; Sawhney and Hankin 1985; Brunn et al. 1985; Rogan et al. 1986). Milk and milk products play a central role in human nutrition. The OCIs are highly lipophilic and easily get accumulated in fatrich milk and milk products, animal meats, etc (Kaphalia et al. 1981; Richard and Dulley 1983; Takroo et al. 1985; Pines et al. 1988). Animal feed, feed mixtures and fodder grasses have been the major source of contamination (Duggan 1968; Kaphalia and Seth, 1982; Pierson et al. 1982; Waliszewski et al. 1985). This paper describes the preliminary observations about the presence of OCIs in commercial cattle feed in India.

Long‐term dietary study and development of no‐observed‐effect level (NOEL) of technical HCH to rats

Daily feeding of technical hexachlorocyclohexane (HCH) (0.5, 5, 25, 250, and 500 mg/kg diet/d) for a period of 360 d to male rats elicited a dose-dependent toxicity, while the dose of technical HCH (0.5 mg/kg diet/d) did not produce signs of intoxication, mortality, organ body weight ratio, enzymatic, and pathomorphological changes. Other doses (5, 25, 250, and 500 mg/kg diet/d) produced significant changes in one or the other parameters studied. Based on this study, it may be suggested that the lowest dose of technical HCH (0.5 mg/kg diet/d) could be considered as the no-observed-effect level in experimental rats.

Residues of 1-naphthol in soil and water samples in and around Bhopal, India.

Carbaryl, a methyl carbamate insecticide, is known for its wide application and low mammalian toxicity. The use of carbaryl in tropical agriculture is of recent origin and the degradation pattern of carbaryl in tropical environment is, thus very scantly. The present report therefore deals with the residues of 1-naphthol present in soil and water samples collected in and around Bhopal, India where carbaryl was commercially produced on large scale for more than a decade.

Assessment of embryo/fetotoxicity and teratogenicity of azadirachtin in rats

To evaluate the potential effect of exposure to azadirachtin technical 12% throughout major organogenesis, rats were fed orally with 500, 1000 and 1500 mg/kg/day azadirachtin on gestation days 6-15 and examined for evidence of embryo/fetotoxicity and teratogenic effects. Technical azadirachtin at different doses did not produce any significant adverse effects in reproductive parameters. Significant embryo/fetotoxic effects were not observed at tested dose levels as evidenced by total number of implantations, post-implantation loss and fetal weight. There were no major malformations, while some minor variants found in high doses were not compound or dose related. The absence of anomalies in fetal gross, visceral morphology and skeleton suggests that technical azadirachtin is not teratogenic in rats at the doses tested.