Bioavailability and influence of ¹4C-carbofuran on Eisenia andrei avoidance, growth and reproduction in treated natural tropical soils.

The bioavailability of carbofuran to the compost worms Eisenia andrei and the influence of its residual amounts on the avoidance, reproduction and growth of this species were studied in two natural tropical soils: a Typic Humaquept (GM) and a Typic Hapludox (LVD), as indicated by the Brazilian environmental authorities for ecotoxicological tests. The worms avoided the soil LVD treated with different doses of carbofuran. The pesticide also affected the production of juvenile specimens in both soils, but cocoon production was reduced only in the GM soil. The earthworms' growth and weight loss were affected by carbofuran (2,2-dimethyl-2,3-dihydro-1-1-benzofuran-7-yl methylcarbamate. CAS number 1563-66-2) only in the LVD and the mortality detected at 56 days of contact with the treated soils was not statistically significant in both of them. Fourteen days after the soil treatment with(14) c-carbofuran, most residues detected in the soils were bound residues (approximately 36% and 30% in the GM and LVD, respectively) and neither mortality nor bioaccumulation was detected in the earthworms, even with absorptions of 13% and 43%, respectively. The LVD soil has lower organic matter content, and the effects of carbofuran on different aspects of the earthworms' life were more pronounced in this soil, most likely due to the higher bioavailability of the pesticide in the soil solution. The results for carbofuran clearly demonstrate that even small quantities of residues do not assure lack of toxicity. They also make evident the necessity of studying the effects of pesticides in natural agricultural soils. Furthermore, as the bound residues and the earthworm contamination are not detected by conventional techniques, they are not taken into account and may be underestimated on environmental risk assessments.

[The investigation into specific features of the distribution of carbofuran in the body of the warm-blooded animals].

The objective of the present study was to estimate the distribution of the carbamate pesticide carfbofuran in the organism of the warm-blooded animals (rats) after its intragastric administration. It was shown that large amounts of unmetabolized carbofuran were present in the internal organs and biological fluids. The highest content of carbofuran was recorded in the stomach, large and small intestines, testicles, urinary bladder, ureters, and heart.

Interactions with DOM and biofilms affect the fate and bioavailability of insecticides to invertebrate grazers.

We studied the fate and bioavailability of insecticides in short-term experiments (48 h) with different hydrophobicity (3.8 pM carbofuran, 3.0 pM lindane, and 5.3 pM chlorpyrifos) across gradients in dissolved organic matter (low-, medium-, and high-DOM) in freshwater microcosms, mimicking runoff events of pesticides. The effects of biofilms were studied by including treatments with biofilms cultivated under different DOM-concentrations. The presence of biofilms negatively affected chlorpyrifos water concentrations, indicating rapid sorption of this hydrophobic pesticide, while lindane concentrations instead increased and carbofuran concentrations were unaffected. Associations of lindane and chlorpyrifos with biofilms were 1.6-2.0 times higher in low- and high-DOM than in medium-DOM treatments, indicating that sorption was affected not only by the quantity, but also by the quality of DOM. Although the proportion of pesticides recovered in biofilms was consistently less than 1 % of added pesticide, pesticide concentrations in biofilms were on average more than 75- (carbofuran) and 382-times (lindane) higher than those in water. Snail accumulation of all three pesticides was significantly affected by DOM-concentrations and correlated to pesticide hydrophobicity, but the relationships were not straightforward. For example, carbofuran uptake in treatments without biofilms was higher in low-DOM than in medium- and high-DOM treatments, while chlorpyrifos uptake instead increased across the DOM-gradient. Biofilms played a role only for the uptake of chlorpyrifos, which decreased markedly in the presence of biofilms. Bioconcentration factors (BCF) calculated for snails and biofilms differed for the three pesticides and were related to their sorption behaviour (i.e., hydrophobicity). The relative proportion of pesticide uptake through biofilm consumption was consistently less than 2 %, showing that passive uptake was by far the predominant uptake pathway for all three pesticides.

A physiologically based pharmacokinetic/pharmacodynamic model for carbofuran in Sprague-Dawley rats using the exposure-related dose estimating model.

Carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl-N-methylcarbamate), a broad spectrum N-methyl carbamate insecticide, and its metabolite, 3-hydroxycarbofuran, exert their toxicity by reversibly inhibiting acetylcholinesterase (AChE). To characterize AChE inhibition from carbofuran exposure, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was developed in the Exposure-Related Dose Estimating Model (ERDEM) platform for the Sprague-Dawley (SD) rat. Experimental estimates of physiological, biochemical, and physicochemical model parameters were obtained or based on data from the open literature. The PBPK/PD model structure included carbofuran metabolism in the liver to 16 known metabolites, enterohepatic circulation of glucuronic acid conjugates, and excretion in urine and feces. Bolus doses by ingestion of 50 microg/kg and 0.5 mg/kg carbofuran were simulated for the blood and brain AChE activity. The carbofuran ERDEM simulated a half-life of 5.2 h for urinary clearance, and the experimental AChE activity data were reproduced for the blood and brain. Thirty model parameters were found influential to the model outputs and were chosen for perturbation in Monte Carlo simulations to evaluate the impact of their variability on the model predictions. Results of the simulation runs indicated that the minimum AChE activity in the blood ranged from 29.3 to 79.0% (as 5th and 95th percentiles) of the control level with a mean of 55.9% (standard deviation = 15.1%) compared to an experimental value of 63%. The constructed PBPK/PD model for carbofuran in the SD rat provides a foundation for extrapolating to a human model that can be used for future risk assessment.

Influence of suspended solids on acute toxicity of carbofuran to Daphnia magna: II. An evaluation of potential interactive mechanisms.

It has been demonstrated that simultaneous exposure of Daphnia magna to suspended solids and a carbamate pesticide potentiates the toxic response to the pesticide. The toxicodynamics between these stressors were investigated to determine possible mechanisms of interaction. Three experimental series were conducted with D. magna to determine: the effect of food availability on carbofuran toxicity; the effect of food availability on jointly administered carbofuran and suspended solids; and changes in the magnitude of effects which can occur with suspended solids of different composition. These experiments demonstrated that both carbofuran toxicity and the joint toxicity of carbofuran and suspended solids to D. magna can be modulated by food availability. While it is clear that food dilution could contribute to energy stress, it appears likely that additional interactive processes also contribute to the observed synergism between carbofuran and suspended solids. Additionally, decomposed peat was shown to be less of a stressor to these pelagic invertebrates than inorganic subsoil.

Species variation in pesticide-induced blood-brain barrier dysfunction.

Neurological disorders following acute or chronic exposure to pesticides have been reported in a number of human cases. However, the mechanism(s) by which pesticides produce central nervous system dysfunction is not clear. The objective of the present study was to examine the functional status of blood-brain barrier (BBB) in rats and mice exposed to selected pesticides of different chemical groups. Adult male albino rats and mice were exposed (1/10 of LD50) daily to dichlorvos (organophosphate), lindane (organochlorine) and carbofuran (carbamate) through oral intubation for 3 days. The status of BBB was evaluated by determining brain sodium fluorescein dye uptake and brain uptake index (BUI) in relation to serum dye level. The brain dye uptake and BUI in pesticide-exposed rats did not differ significantly in comparison to that of controls. However, brain dye uptake and BUI were increased significantly in mice exposed to dichlorvos (85%, 40%), lindane (79%, 26%) and carbofuran (129%, 61%). The results of this study show that mouse BBB system is more sensitive to pesticide-induced breach as compared to that of rat. These variations may have a role in determining the outcome of pesticide neurotoxicity in different species.

Effect of bleomycin-induced fibrosis on pulmonary metabolism of selected xenobiotics.

Few studies are available characterizing the effects of fibrosis on pulmonary disposition of drugs or environmental pollutants. Two model substrates, p-nitroanisole and carbofuran, were selected to evaluate the effect of bleomycin-induced fibrosis on pulmonary disposition and metabolism using the isolated perfused lung and in vitro enzyme preparations. The rate of p-nitroanisole oxidation in the isolated perfused lung was significantly lower in fibrotic (k = 0.0334 min-1) than in control (k = 0.0493 min-1) lungs. However, there was no difference in the amount of p-nitrophenol formed between control (38 +/- 4 micrograms) and fibrotic (47 +/- 7 micrograms) lungs. Carbofuran clearance was similar in control (t1/2 = 91 min, ke = 0.008 min-1) and fibrotic (t1/2 = 75 min, ke = 0.009 min-1) lungs and was consistent with a one-compartment model. The Km value for p-nitrophenol formation in microsomes (0.185 +/- 0.095 mM) from control lungs was similar to fibrotic lungs (0.054 +/- 0.014 mM); however, Vmax was significantly higher in healthy (34.6 +/- 6.3 pmoles/min per mg microsomal protein) than in fibrotic (11.16 +/- 3.19 pmoles/min per mg microsomal protein) lungs. In vitro carbofuran studies indicated limited metabolism of carbofuran in both healthy and fibrotic microsomal enzyme preparations (< 5% of the administered dose). Lower p-nitroanisole metabolism in fibrotic lungs was consistent with lower levels of cytochrome P-450 2B1/B2 measured in bleomycin-treated lungs. Results suggest that individuals with bleomycin-induced pulmonary fibrosis may be at greater risk when exposed to certain toxic environmental chemicals or drugs that require detoxification by pulmonary microsomal enzymes.

Cytogenetic biomarkers of carbofuran toxicity utilizing human lymphocyte cultures in vitro.

Short-term lymphocyte cultures from human peripheral blood samples were incubated with various aliquots of the carbofuran pesticide. After 48 h of initiation and 24 h of exposure to the carbofuran pesticide aliquots, it was seen that carbofuran caused an increase in the frequency of chromosomal aberrations, and the increase was significant (p < 0.05) in treated samples compared to controls. Karyotype analysis revealed more satellite associations, gaps, and breaks in treated samples. Single-strand breaks in the DNA assessed by comet assay revealed that the pesticide caused increase in the comet tail length implicating genotoxicity in somatic cells. The LD(50) of carbofuran was found to be 18 microM as calculated by probit analysis and determined by trypan blue dye exclusion method. The results presented here indicate that in vitro assays could be used as indicators of cyto- and genotoxicity of the pesticide, and their end points could be used as biomarkers.

Adsorption mechanisms of carbofuran on silica: structure, kinetics, and solubility influence.

The adsorption processes of carbofuran from solutions in pure water onto silica (Aerosil 200) have been determined in order to bring greater coherence to previous results obtained directly on soils. Adsorption isotherms and their evolution with temperature reveal that adsorption is generally weak, increases with temperature, and does so significantly with concentration when the solubility limit is approached. Kinetics of dissolving, of adsorption on silica, and of desorption all obey an irreversible two-compartment model. Desorption rate is slower than adsorption rate. Consequences on the behavior of carbofuran in the environment are discussed.

Dermal penetration of carbofuran in young and adult Fischer 344 rats.

Dermal penetration of carbofuran was determined in young (33 d) and adult (82 d) female Fischer 344 rats employing in vivo and in vitro methods. In vivo dermal penetration at 120 h was 43% for young and 18% for adult rats. The half-time for carbofuran skin penetration (in vivo) was 128 h for the young and 400 h for the adults. The young to adult ratio of dermal penetration was greater than 1 at all time points (average 2.9) and had a maximum of 4.2 at 24 h. Cumulative urinary excretion approached about 95% of the absorbed dose in both the young and adult animals at 120 h. Whole-body retention was slightly higher in adults. Kidney showed the highest tissue-to-blood concentration ratio (4.6 in adult, 2.3 in young). The ratio for the carcass was 2.8 in the adult and 2.4 in the young. The urine/blood concentration ratio was high, 435 in the adult and 573 in the young. The feces/blood ratio was 44 in the adult and 65 in the young. Skin absorption by the in vitro continuous-flow system was 41% for the young and 11% for the adult at 72 h, compared to 36% and 13% by the in vivo method. The static in vitro method gave consistently lower skin penetration values of 12% for the young and 8.8% for the adult. Differences in the kinetics of retention and excretion were observed between the young and adult animals.

Response of the paddy field cyanobacterium Anabaena doliolum to carbofuran.

Assessment of the influence of carbofuran on the nontarget cyanobacterium Anabaena doliolum revealed that this sheathless heterocystous form of cyanobacteria was more sensitive to the insecticide carbofuran. Anabaena doliolum was initially able to utilize low concentrations of carbofuran, whereas higher concentrations and the subsequent formation of hydrolytic breakdown products were toxic. Growth inhibition reached more than 50% by treatment with 80 and 100 ppm of the insecticide. Nitrogenase activity of the cyanobacterium was reduced by 38% after 48 h by treatment with 100 ppm carbofuran with no observed change in heterocyst frequency. Toxicity of the insecticide was the highest at pH 4-6 (46-59%) and the lowest at pH 7-10 (12-27%) due to the persistence of carbofuran and the resulting alkaline-catalyzed hydrolysis associated with the water regime of the rice fields. Doubling the initial population level of the cyanobacterium reduced the toxicity of the insecticide.

Carbofuran transfer and persistence in drained agricultural soils related to their structure and adsorption properties.

Carbofuran (Curater 5G) behavior was studied in two drained cornfield soils, clay and loamy-clay, for 2 successive years. Different dissipations were observed in each soil for the same time period (8 weeks in 1985, 9 weeks in 1986). The authors found drained water from organic mater-rich soil to possess a higher carbofuran content, with 7.1-13.7 and 2.5-5.0% of the applied dose for clay and loamy-clay soils, respectively. The major part of these percentages arose from the drained waters associated with rainfall occurring during the first 2-3 weeks after application. Laboratory experiments confirmed the influence of the soil structure and its properties on carbofuran adsorption, and consequently on carbofuran leaching under field conditions.

In vitro dermal penetration study of carbofuran, carbosulfan, and furathiocarb.

In this study, the dermal penetration rate of carbofuran, carbosulfan, and furathiocarb has been measured with rat abdominal skin using the static diffusion cell. The technical grades of three compounds were applied at different doses on skin surface mounted in static diffusion cell and incubated at 32 degrees C for 48 h with shaking. The same procedures were carried out with furathiocarb EC (emulsifiable concentrate) and WP (wettable powder). At regular intervals, the receptor fluid in cell was sampled and analyzed by HPLC. Only carbofuran was found in carbosulfan- or furathiocarb-treated samples, suggesting they converted into carbofuran while passing through the skin layer. The quantity of insecticide penetrating skin increased with time and applied dose. The skin penetration rate increased with the water solubility of insecticides. The dermal penetration rates of carbofuran, furathiocarb, and carbosulfan were determined as 1.05 micro g/cm(2) per h ( r(2)=0.991), 0.46 micro g/cm(2) per h ( r(2)=0.984) and 0.14 micro g/cm(2) per h ( r(2)=0.967), respectively. There was no significant difference in rate of skin penetration between furathiocarb EC (1.42 micro g/cm(2) per h, r(2)=0.988) and WP (1.35 micro g/cm(2) per h, r(2)=0.982), while furathiocarb technical grade showed a lower skin penetration rate. In vitro models may be used to predict percutaneous absorption and are useful in selecting safer formulations for field application of pesticide.

Bioavailability to rats and toxicity in mice of carbofuran residues bound to faba beans.

14C-carbofuran penetrated readily into seeds of Vicia faba and the rate of penetration was found to be dose dependent. The percentage of bound residues was generally low and did not exceed 3% of the applied dose. When the bound residues were fed to rats 46% of the radioactivity was eliminated via CO2 and urine, while tissues contained 25%. Carbofuran phenol and 3-hydroxy carbofuran represented the main metabolites in the urine. These data indicate that bean-bound carbofuran residues are highly bioavailable to rats. Feeding mice with bound carbofuran residues for 90 days led to inhibition of erythrocyte cholinesterase activity after 30 days (35-40%) while the plasma enzyme remained unaffected. Serum transaminases and blood urea nitrogen were significantly elevated, indicating injury to hepatic and renal structures. The results strongly suggest that the bound residues can induce adverse biological effects in mice.