benzofurans and deltanit

Several types of pesticides, such as organophosphates, phenoxyacetic acid, and carbamate have a high risk of affecting human health, causing allergic rhinitis and bronchial asthma-like diseases. We used our long-term sensitization method and a local lymph node assay to examine the allergic reactions caused by several types of pesticides. BALB/c mice were topically sensitized (9 times in 3 weeks), then challenged dermally or intratracheally with 2,4-D, BRP, or furathiocarb. One day post-challenge, the mice were processed to obtain biologic materials for use in assays of total IgE levels in serum and bronchoalveolar lavage fluid (BALF); differential cell counts and chemokine levels in BALF; lymphocyte counts and surface antigen expression on B-cells within regional lymph nodes (LNs); and, ex situ cytokine production by cells from these LNs. 2,4-D-induced immune responses characteristic of immediate-type respiratory reactions, as evidenced by increased total IgE levels in both serum and BALF; an influx of eosinophils, neutrophils, and chemokines (MCP-1, eotaxin, and MIP-1beta) in BALF; increased surface antigen expression on B-cells IgE and MHC class II production) in both auricular and the lung-associated LNs; and increased Th2 cytokine production (IL-4, IL-5, IL-10, and IL-13) in both auricular and the lung-associated LN cells. In contrast, BRP and furathiocarb treatment yielded, at most, non-significant increases in all respiratory allergic parameters. BRP and furathiocarb induced marked proliferation of MHC Class II-positive B-cells and Th1 cytokines (IL-2, TNF-alpha, and IFN-gamma) in only auricular LN cells. These results suggest that 2,4-D is a respiratory allergen and BRP and furathiocarb are contact allergens. As our protocol detected classified allergic responses to low-molecular-weight chemicals, it thus may be useful for detecting environmental chemical-related allergy.

Topics: 2,4-Dichlorophenoxyacetic Acid; Administration, Cutaneous; Administration, Inhalation; Allergens; Animals; Benzofurans; Bronchoalveolar Lavage Fluid; Carbamates; Cell Proliferation; Chemokines; Cytokines; Dermatitis, Allergic Contact; Dose-Response Relationship, Drug; Female; Immunoglobulin E; Leukocyte Count; Local Lymph Node Assay; Lymph Nodes; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Organophosphorus Compounds; Pesticides; Respiratory Hypersensitivity

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.

Topics: Administration, Cutaneous; Animals; Benzofurans; Carbamates; Carbofuran; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; In Vitro Techniques; Insecticides; Male; Rats; Rats, Sprague-Dawley; Skin; Skin Absorption; Solubility

The pharmacokinetics of furathiocarb were studied in vivo in male Sprague-Dawley rats following dermal treatment. HPLC and post-column derivatization were used for the analysis of furathiocarb and its metabolites (carbofuran, 3-hydroxycarbofuran and 3-ketocarbofuran). Carbofuran and 3-hydroxycarbofuran were detected in plasma and urine rather than furathiocarb. 3-Ketocarbofuran, another potential metabolite, was not observed in any sample. The concentration of carbofuran was higher than that of 3-hydroxycarbofuran in plasma, but the reverse was the case in urine. The corresponding area under the plasma concentration-time curve, Tmax, and Cmax values of carbofuran and 3-hydroxycarbofuran for 1500 mg kg-1 doses were 2.4-8.0 mg equiv hml-1, 12 h and 0.1-0.4 mg equiv ml-1, respectively. T1/2 was calculated only for 3-hydroxycarbofuran (28 h). Two metabolites were excreted in a dose-dependent manner without saturation.

Topics: Administration, Cutaneous; Animals; Area Under Curve; Benzofurans; Carbamates; Carbofuran; Chromatography, High Pressure Liquid; Half-Life; Insecticides; Male; Rats; Rats, Sprague-Dawley; Skin

Seven cases involving acute fatalities due to ingestion of furathiocarb, a carbamate insecticide, are presented. Furathiocarb was detected in the gastric contents using thin layer chromatography (TLC) and gas chromatography/mass spectrophotometry (GC/MS), and quantified in the blood using a gas chromatograph equipped with a nitrogen-phosphorus detector (NPD). The fatal levels of furathiocarb in the blood ranged from 0.1 to 21.6 micrograms/ml.

Topics: Acute Disease; Adolescent; Adult; Aged; Autopsy; Benzofurans; Carbamates; Cause of Death; Chromatography, Thin Layer; Female; Gas Chromatography-Mass Spectrometry; Humans; Insecticides; Male; Middle Aged; Suicide

The carbamate insecticides benfuracarb, carbosulfan and furathiocarb were investigated in the mouse bone marrow micronucleus assay to establish whether they show cytogenetic activity in vivo. Two doses of each substance were administered intraperitoneally to NMRI mice. All of the three substances led to a positive micronucleus response in polychromatic erythrocytes of the bone marrow at different expression times. While furathiocarb and carbosulfan showed similar patterns of the time-dependence of the micronucleus formation with maximum values after 72 h, benfuracarb exhibited a different behaviour with the maximum increase taking place within 24 h after substance application. In furathiocarb-treated animals the ratio of normochromatic to polychromatic erythrocytes showed a dose and time depending increase with the highest value obtained after 72 h in animals treated with the upper dose. The two yeast test systems Saccharomyces cerevisiae strains D7 and D61.M were applied in order to evaluate the genetic endpoints gene mutation, gene conversion and aneuploidy induction. None of the three insecticides had an influence on the frequencies of gene conversion and reverse mutation in the yeast S. cerevisiae D7 when tested with and without metabolic activation. In strain D61.M however benfuracarb and furathiocarb led to an increase of chromosome loss in the presence of the S9 metabolizing system.

Topics: Animals; Benzofurans; beta-Alanine; Biotransformation; Bone Marrow Cells; Carbamates; Chromosome Deletion; Dose-Response Relationship, Drug; Erythrocytes; Female; Injections, Intraperitoneal; Insecticides; Male; Mice; Micronucleus Tests; Microsomes, Liver; Mutagenicity Tests; Mutagens; Saccharomyces cerevisiae