Effect of carbaryl on cultured embryonic chicken gonads in vitro]

Ovaries and testes from 9 day-old chick embryos have been explanted on media containing various levels of carbaryl. The pesticide action depends on the use doses. Histocytopathological effects were essentially observed upon gonocytes which degenerated.     

Immunotoxicity of monoclonal antibodies

Monoclonal antibodies (mAbs) are large molecules intended to bind to specific targets often expressed on the immune system, and to treat various immunopathological conditions. Therefore, mAbs can be considered to have a high potential for immunotoxicity, which is reflected in the clinical experience accumulated on mAbs-induced adverse effects related to immunosuppression, immunostimulation and hypersensitivity (immunogenicity). So far, non clinical immunotoxicity studies have been inadequate to address all safety issues in relation to the possible immunotoxicity of mAbs, because they are fraught with limitations and pitfalls primarily related to the lack of relevant animal species. In addition, clinical studies rarely include validated end-points dedicated to the prediction of immunotoxicity. With the ongoing development of mAbs as novel therapeutic strategies for a wide variety of diseases, efforts should be paid to improve our understanding of mAbs-induced immunotoxic effects and design dedicated strategies to assess their immunological safety, both non clinically and clinically.Key words: immunotoxicology, monoclonal antibodies, immunological safety evaluation     

Immunotoxicity of monoclonal antibodies

Monoclonal antibodies (mAbs) are large molecules intended to bind to specific targets often expressed on the immune system, and to treat various immunopathological conditions. Therefore, mAbs can be considered to have a high potential for immunotoxicity, which is reflected in the clinical experience accumulated on mAbs-induced adverse effects related to immunosuppression, immunostimulation, and hypersensitivity (immunogenicity). So far, non clinical immunotoxicity studies have been inadequate to address all safety issues in relation to the possible immunotoxicity of mAbs, because they are fraught with limitations and pitfalls primarily related to the lack of relevant animal species. In addition, clinical studies rarely include validated end-points dedicated to the prediction of immunotoxicity. With the ongoing development of mAbs as novel therapeutic strategies for a wide variety of diseases, efforts should be paid to improve our understanding of mAbs-induced immunotoxic effects and design dedicated strategies to assess their immunological safety, both non clinically and clinically.     

Immunotoxicity of phosphamidon following subchronic exposure in albino rats

Effect of subchronic doses of phosphamidon exposure on humoral and cell mediated immune (CMI) responses were studied in male albino rats using SRBC, ovalbumin and KLH as antigens. Humoral immune responses were assessed by estimating antibody titre against antigen and splenic plaque forming cells (PFC) assay. CMI responses were studied by using leucocyte migration inhibition (LMI), macrophage migration inhibition (MMI) and delayed type hypersensitivity (DTH) response. Results obtained in the present study revealed marked suppression of humoral and CMI responses in a dose dependent pattern. Hence, suppression of immune responses by phosphamidon even at subchronic doses is clearly an important aspect for its safety evaluation.     

Immunotoxicity of Copper Alginate Fibers in Guinea Pigs and Mice

The relation between copper alginate fibers and immunotoxicity in animals was studied by dividing guinea pigs and mice into control groups and experimental groups. Varied weights of fibers were subcutaneously embedded in the experimental groups, whereas the control groups were operated on simulatively. Morphology analysis, erythrocyte osmotic fragility (EOF) test, direct plaque-forming cell (PFC) assay, quantitative hemolysis spectrophotometry (QHS) assay, macrophages phagocytosis assay, and pathology analysis were used to examine morphology, microstructure, and immunotoxicity. With increasing doses of copper alginate fibers, the EOF of experimental groups increased in contrast with the control group. Moreover, the antibody level decreased based on the results of the PFC and QHS assays, and macrophages phagocytosis descended in relation to dose. However, the immune functions were weakened without time dependence. According to pathologic photographs, the partial organs were damaged, implying bad histocompatibility. Hence, copper alginate fiber is proved to be a harmful material for medical devices.     

Interactions of carbaryl with estuarine bacterial communities

The addition of carbaryl (100g/ml) to a model estuarine ecosystem did not affect the number of bacteria in the sediment, but reduced the diversity (as measured by the rarefaction technique) of the microbial community as compared with a control model ecosystem. Two carbaryltolerant strains of bacteria were isolated from the carbaryl-treated system, but none were isolated from the control system. Bacterial growth and filter paper decomposition in mixed cultures was prevented by 100g/ml carbaryl, but this amount had no effect on the extracellular cellulase of an estuarine isolate. Increasing the amount of organic matter in the medium attenuated the toxicity of carbaryl to pure cultures of an estuarine isolate. The addition of 1, 10, or 100g/ml carbaryl to field plots had no effect on bacterial numbers, diversity, or filter paper decomposition. The amount of carbaryl in sediments exposed to 100g/ml fell below the limit of detection by thin-layer chromatography within 12 hours. In sterile and nonsterile model systems, carbaryl rapidly adsorbed to sediment, and hydrolyzed to 1-naphthol in both sediment and water. Although carbaryl may be toxic to bacteria under some conditions, the amounts that might enter and persist in an estuary are insufficient to have a significant impact on the sediment microbial community.     

Hydrolysis of carbaryl by a Pseudomonas sp. and construction of a microbial consortium that completely metabolizes carbaryl

Two Pseudomonas spp. (isolates 50552 and 50581) isolated from soil degraded 1-naphthol and carbaryl, an N-methylcarbamate pesticide, respectively. They utilized these compounds as a sole source of carbon. 1-Naphthol was completely metabolized to CO2 by the isolate 50552, while the carbaryl was first hydrolyzed to 1-naphthol and then converted into a brown-colored compound by the isolate 50581. The colored metabolite was not degraded, but 1-naphthol produced by the isolate 50581 during the exponential phase of growth was metabolized by the isolate 50552. The two isolates were used to construct a bacterial consortium which completely catabolized carbaryl to CO2. No metabolite was detected in the cell cultures of the consortium. The isolate 50581 harbored a 50-kb plasmid pCD1, while no plasmid was detected in the isolate 50552. The isolated bacteria individually or as a consortium may be used for detoxification of certain industrial and agricultural wastes.     

Transient phase calibration of tyrosinase-based carbaryl biosensor

The inhibition of tyrosinase, used as a selective compound in amperometric biosensor for the detection of carbaryl and the possibilities of calibration of carbaryl biosensor have been studied. The kinetic analysis of biosensor data was based on the application of the biosensor dynamic model, allowing a quick calculation of independent on each other kinetic and steady-state parameters. It was found that carbaryl acts as an inhibiting substrate of tyrosinase and at low concentrations accelerates the tyrosinase-catalyzed oxidation of tyrosine by dissolved oxygen. The reaction mechanism is analogous to that usually considered for uncompetitive inhibition and the plot of kinetic parameter as a function of carbaryl concentration has a flat asymmetric maximum. Consequently, the kinetic parameter alone is not sufficient for the calibration of carbaryl biosensor and simultaneous application of other carbaryl-dependent parameters, like steady-state parameter, is essential.     

Hydrolysis of carbaryl by a Pseudomonas sp. and construction of a microbial consortium that completely metabolizes carbaryl.

Two Pseudomonas spp. (isolates 50552 and 50581) isolated from soil degraded 1-naphthol and carbaryl, an N-methylcarbamate pesticide, respectively. They utilized these compounds as a sole source of carbon. 1-Naphthol was completely metabolized to CO2 by the isolate 50552, while the carbaryl was first hydrolyzed to 1-naphthol and then converted into a brown-colored compound by the isolate 50581. The colored metabolite was not degraded, but 1-naphthol produced by the isolate 50581 during the exponential phase of growth was metabolized by the isolate 50552. The two isolates were used to construct a bacterial consortium which completely catabolized carbaryl to CO2. No metabolite was detected in the cell cultures of the consortium. The isolate 50581 harbored a 50-kb plasmid pCD1, while no plasmid was detected in the isolate 50552. The isolated bacteria individually or as a consortium may be used for detoxification of certain industrial and agricultural wastes.     

Immunotoxicity of soluble and insoluble salts of cadmium instilled intratracheally

Rats were intratracheally (i.t.) exposed to 36.5 or 27.5 microg of cadmium (Cd) as soluble cadmium chloride (CdCl2) and insoluble cadmium oxide (CdO) salts. The retention of metal in lungs, liver and kidney was assessed by atomic adsorption spectrophotometer. The animals were intraperitoneally (i.p.) primed with sheep red blood cells (SRBC) and assessed for the number of antibody forming cells in lung associated lymph nodes (LALN) and spleen. Both the compounds had similar retention of metal in lungs but CdO induced more pulmonary inflammatory and degradative changes than CdCl2. The larger influx of polymorphonuclear cells (PMNs) following CdO exposure appears to be due to the absence of protection afforded by Cd induced metallothionein cytoplasmic protein while the Cd metallothionein complex formed in the case of CdCl2 is more protective. However both forms of Cd had similar local immunosuppressive potential but CdO had more prolonged suppressive effect.     

Cholinesterase activity in Japanese quail dusted with carbaryl.

Japanese quail (Coturnix coturnix japonica) were dusted with 5% carbaryl to determine if this topical treatment would alter plasma and brain cholinesterase activities. Within 6 hours after dusting, plasma cholinesterase activity was depressed compared with controls, the depression averaging 20% for females and 27% for males. By 24 hours the cholinesterase activity of females had returned to normal, but the cholinesterase activity of males remained depressed. Brain cholinesterase activity was not affected by the treatment, and there were no overt toxic signs.     

Catalytic antibody therapy against the insecticide carbaryl

Catalytic antibodies have been studied widely, but little is known about their applicability as therapeutic reagents in vivo. Here we report that carbaryl, a widely used broad-spectrum carbamate insecticide that is toxic to animals and humans, is hydrolyzed by polyclonal catalytic antibodies induced in vivo by a phosphate immunogen. To test the efficacy of the in vivo-induced polyclonal antibodies, we immunized mice with the phosphate immunogen and assayed their sensitivity to carbaryl by determining the ED(50) value, the dose that produces lowest-grade tremors in 50% of animals. We found that the ED(50) for immunized mice was 43% higher than that for nonimmunized mice and that this increase in ED(50) probably resulted from the hydrolysis of carbaryl by the catalytic antibodies in vivo. Our results suggest that polyclonal catalytic antibodies can be used as therapeutic reagents in vivo.     

Recovery of carbaryl inhibited AChE in penaeid prawn, Metapenaeus monoceros

The acetylcholinesterase activity in selected tissues of prawn, Metapenaeus monoceros showed a significant inhibition during commercial (CgC) and technical (TgC) grade carbaryl exposure. The rate of inhibition of AChE in nervous and non-nervous tissues is more under CgC over TgC exposure, suggests the involvement of emulsifier system for easy penetration of CgC molecule, which is absent in TgC. A progressive recovery of AChE activity from TgC and CgC induced inhibition was in the tissues within 10 days after the transfer of prawns to toxicant free water i.e., recovery or reclamation period. From the study, it has been observed that the inhibition of AChE activity is still persists evenafter 10 days of reclamation period, gives the idea of carbaryl accumulation at the cellular level or the reclamation period is not sufficient for the restoration of normalcy of AChE activity.     

Metabolism of 1-naphthyl-N-methyl carbamate (carbaryl) by bacterial isolates from honey bees and the effect of bacterial inoculations on carbaryl tolerance in bees

I.D. SHARMA AND A. NATH. 1996. The bacteria which inhabit the body of foragers of Apis cerana indica F. were evaluated for degradation of carbaryl (1-naphthyl- N -methyl carbamate). Citrobacter sp., Enterobacter aerogenes and an unidentified isolate could utilize carbaryl as sole carbon and energy source. The enrichment cultures of bacteria could degrade carbaryl 0.019–0.082 in nutrient broth and 0.111–7.895 mg μg^-1 bacterial dry wt in basal salts medium of 1 mmol 1^-1 carbaryl. 1-Naphthol was the major product of carbaryl degradation. The dip and injection inoculations of foragers ( Apis cerana indica F. and Apis mellifera L.) with these bacteria resulted in a significant increase in tolerance to carbaryl. The application of mixed culture to bees induced higher tolerance than the individual isolates. This is the first report of the use of bacteria to decontaminate a living system.     

Phagocytosis as a Biomarker of Immunotoxicity in Wildlife Species Exposed to Environmental Xenobiotics

In the present paper, we are reviewing experimental evidencedemonstrating that phagocytic cells, such as macrophages, maybe used as a biomarker of immunotoxicity in wildlife studies.We will first present data obtained after exposure in vitrowith selected chemicals showing the comparative sensitivityof phagocytic cells from different species. These results demonstratethat, at least for metals, each species produce a similar shapeddose-response curve, although considerate interspecies sensitivityis evident. These results also demonstrate the sensitivity ofthe phagocytic activity, suggesting indeed that this functioncould be used to monitor exposure to chemicals. The similarshaped dose-response curves imply that mechanisms of actionmay also be similar. Furthermore, based on the relative speicessensitivity, sentinel species could be selected for field monitoring.Such an approach may also be useful to establish correctionfactors required to extrapolate results between species. Thissensitivity of the phagocytic activity of macrophages will befurther under controlled conditions in laboratory animal models.Finally, the reliability of this approach will be demonstratedusing case studies with wildlife species.