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Cytogenetic effects of an agricultural antibiotic, captan, on mouse bone marrow and testicular cells.

This paper deals with the cytogenetic effects of Captan on mouse bone marrow and testis. We used (a) the assays of micronuclei (MN) in polychromatic erythrocytes (PCE), (b) the mouse chromosomal aberration test on bone marrow and testis, and (c) the assay of sperm morphology. The tested doses in these assays were 1000, 800, 400, 100, and 50 mg/kg. The results showed that Captan was remarkably mutagenic to bone marrow, the lowest dose inducing MN being 100 mg/kg, and to chromosome breakage, 400 mg/kg. It was also demonstrated that captan was mutagenic to cells of the mouse testis; there was a certain relationship between dosage and response. The lowest doses inducing mutagenicity of spermatocyte and primary spermatogonia and sperm-head abnormality were 50, 800, and 200 mg/kg, respectively.

Animals↗

Optical biosensor consisting of glutathione-S-transferase for detection of captan.

The optical biosensor consisting of a glutathione-S-transferase (GST)-immobilized gel film was developed to detect captan in contaminated water. The sensing scheme was based on the decrease of yellow product, s-(2,4-dinitrobenzene) glutathione, produced from substrates, 1-chloro-2,4-dinitrobenzene (CDNB) and glutathione (GSH), due to the inhibition of GST reaction by captan. Absorbance of the product as the output of enzyme reaction was detected and the light was guided through the optical fibers. The enzyme reactor of the sensor system was fabricated by the gel entrapment technique for the immobilized GST film. The immobilized GST had the maximum activity at pH 6.5. The optimal concentrations of substrates were determined with 1 mM for both of CDNB and GSH. The optimum concentration of enzyme was also determined with 100 microg/ml. The activity of immobilized enzyme was fairly sustained during 30 days. The proposed biosensor could successfully detect the captan up to 2 ppm and the response time to steady signal was about 15 min.

Biosensing Techniques↗

Dermal penetration of [14C]captan in young and adult rats.

Age dependence in dermal absorption has been a major concern in risk assessment. Captan, a chloroalkyl thio heterocyclic fungicide, was selected for study of age dependence as representative of this class of pesticides. Dermal penetration of [14C]captan applied at 0.286 mumol/cm2 was determined in young (33-d-old) and adult (82-d-old) female Fischer 344 rats in vivo and by two in vitro methods. Dermal penetration in vivo at 72 h was about 9% of the recovered dose in both young and adult rats. The percentage penetration was found to increase as dosage (0.1, 0.5, 2.7 mumol/cm2) decreased. Two in vitro methods gave variable dermal penetration values compared with in vivo results. A static system yielded twofold higher dermal penetration values compared with in vivo results for both young and adult rats. A flow system yielded higher dermal penetration values in young rats and lower penetration values in adults compared with in vivo results. Concentration in body, kidney, and liver was less in young than in adult rats given the same absorbed dosage. A physiological pharmacokinetic model was developed having a dual compartment for the treated skin and appeared to describe dermal absorption and disposition well. From this model, tissue/blood ratios of captan-derived radioactivity for organs were found to range from 0.35 to 3.4, indicating no large uptake or binding preferences by any organ. This preliminary pharmacokinetic model summarizes the experimental findings and could provide impetus for more complex and realistic models.

Administration, Cutaneous↗

Influence of bacterial growth of the overnight culture on the captan- and folpet-induced reversion in the Ames test.

The influence of the stage of bacterial growth of the overnight culture on captan- and folpet-induced reversion in the Ames test was investigated. Tests were performed in order to determine both the number of viable bacteria at different intervals of bacterial growth--in the presence or absence of captan and folpet--and also the number of revertants. Captan or folpet were tested at 5 micrograms per plate, a concentration which had previously showed a mutagenic effect to the TA100 strain. The highest induced reversion was obtained when the bacterial culture used had entered the stationary-phase after 10-14 h, with a titre of at least 10(8) viable cells per ml.

Bacteria↗

Urine mutagenicity and lymphocyte DNA damage in fruit growers occupationally exposed to the fungicide captan.

AIMS: To determine haematological parameters, urine mutagenicity (on three Salmonella typhimurium strains), and DNA damage (using the comet assay) in mononuclear leucocytes of farmers before and after a one-day spraying period of pear and apple trees with the fungicide captan in usual conditions. METHODS: Fruit growers were exposed to captan during the 1998 (n = 12) and/or the 2000 spraying seasons (n = 17). Biological samples were collected on the morning of the day of spraying (S1), the evening after spraying (S2), and the morning of the day after (S3). The UK Predictive Operator Exposure Model (UK-POEM) was used to quantify pesticide exposure intensity. RESULTS: No effect was observed on haematological parameters for these two spraying seasons. Proportions of mutagenic urine samples did not significantly differ between S1 and S2/S3 sampling points. In contrast with strains TA97a and YG1041 mainly sensitive to frameshift mutations, a positive trend was observed between the difference (S3-S1) of mutagenic power on strain TA102 detecting base-pair mutations and the exposure predicted value given by UK-POEM, mainly due to parameters related to protective clothing. No significant variations in DNA damage levels were observed between S1 and S3, nor were correlations observed with parameters of pesticide exposure. CONCLUSIONS: A one-day spraying period with captan and other pesticides does not significantly induce DNA damages in mononuclear leucocytes. In contrast, an inefficient protective clothing could correlate with an increase in urine mutagenicity as assessed by the TA102 tester strain.

Adult↗

[Acute oral suicidal intoxication with captan--a case report].

According to the best of our knowledge the second case of acute intoxication with captan was described. In this paper a 22-year old female was admitted to the Department of Toxicology with a nausea, weakness, numbness of upper limbs and substernal pain. She said that these symptoms began two hours after suicidal ingestion of 5.0 g of captan. At admission the patient was alert. Temperature was 37 degrees C, heart rate 100-120 b/min., BP 100-120/60-70 mm Hg and breathing rate 17/min. WBC were slightly elevated 12.4 x 10(3)/microl as well as the creatine kinase activity 329 U/L. ECG showed inversion of a T segment in V1-V4 leads. ECHO-sound made in 4th and 120th day after the onset of intoxication showed no changes, with EF--70%. Temporary increase of creatine kinase activity as well as the presence of inverted T segment in V1-V4 leads may suggest cardiotoxic effects of captan during acute intoxication.

Adult↗

Gas chromatographic determination of captan, folpet, and captafol residues in tomatoes, cucumbers, and apples using a wide-bore capillary column: interlaboratory study.

An interlaboratory study of the determination of captan, folpet, and captafol in tomatoes, cucumbers, and apples was conducted by 4 laboratories using wide-bore capillary column gas chromatography with electron capture detection. The 3 fungicides were determined using the Luke et al. multiresidue method modified to include additional solvent elution in the optional Florisil column cleanup step used with this method. The crops were fortified with each fungicide at 3 levels per crop. Mean recoveries ranged from 86.2% for a 25.1 ppm level of captan in apples to 115.4% for a 0.288 ppm level of captafol in apples. Interlaboratory coefficients of variation ranged from 3.4% (24.7 ppm folpet) to 9.7% (0.243 ppm captafol) for tomatoes; from 2.8% (2.0 ppm captafol) to 8.2% (24.8 ppm captan) for cucumbers; and from 1.5% (0.234 ppm folpet) to 22.1% (0.266 ppm captafol) for apples.

Captan↗

Gas-liquid chromatographic determination of captan and two metabolites in milk and meat.

A gas-liquid chromatographic (GLC) method has been developed for the determination of captan (N-trichloromethylthio-4-cyclohexene-1,2-dicarboximide) and 2 metabolites, tetra-hydrophthalimide (THPI) and tetrahydrophthalamic acid (THPMA), in milk and meat. The sample is extracted with ethyl acetate and is cleaned up by acetonitrile partition and silica gel chromatography where captan, THPI, and THPMA are separated. Captan is directly determined by GLC. THPI and THPMA are separately derivatized in an acetone solution of pentafluorobenzyl bromide. The resultant derivatives are purified separately on an Al2O3 column and quantitated by GLC, using an electron capture detector. Recoveries from milk samples fortified at 0.02-10 ppm ranged from 71 to 102%; recoveries from meat samples fortified at 0.04-10 ppm ranged from 75 to 99%.

Animals↗

[Resistance of earthworms Lumbricus terrestris and Allolobophora turgida to the fungicide captan 50 W.P].

Two species of earthworms were kept in Muck, Chicot and Ste-Sophie soils treated with captan 50 W.P. solutions of 700, 1 400 and 2 800 ppm. After a 42-day treatment period, L. terrestris had a 95% survival and A. turgida 100% survival. Using a gas chromatograph method, no captan was detected in tissue extracts of exposed earthworms. Based on the survival rate and the undetected presence of captan in earthworm tissues, we concluded that soil residues of this product are unlikely to be harmful to the animal's ecology.

Animals↗

Bioassay of captan for possible carcinogenicity.

A bioassay of technical-grade captan for possible carcinogenicity was conducted by administering the test material in feed to Osborne-Mendel rats and B6C3F1 mice. Groups of 50 rats of each sex were administered one of two doses of captan for 80 weeks, then observed for 33 or 34 weeks. The time-weighted average doses for both sexes of rats were 2,525 or 6,050 ppm. Matched controls consisted of groups of 10 untreated rats of each sex; pooled controls, used for statistical evaluation, consisted of the matched controls combined with 75 untreated male and 75 untreated female rats from similar bioassays of six other test chemicals. All surviving rats were killed at 113-114 weeks. Groups of 50 mice of each sex were administered the test material at one of two doses, either 8,000 or 16,000 ppm, for 80 weeks, then observed for 11 weeks. Matched controls consisted of groups of 10 untreated mice of each sex; pooled controls, used for statistical evaluation, consisted of the matched controls combined with 80 untreated male and 80 untreated female mice from similar bioassays of six other test chemicals. All surviving mice were killed at 90-91 weeks. The mean body weights of both low- and high-dose rats and high-dose mice were lower than those of the matched controls throughout most of the study. Mortality rates did not show statistically significant dose-related trends in either sex of either species. In rats, a positive dose-related trend and a difference between incidences of tumors in high-dose and pooled-control groups were found in females when the data for adrenal cortical adenoma were combined with those for adrenal cortical carcinoma (pooled controls, 0/64, low-dose 2/50, high-dose 3/47, P=0.047). There was also a positive dose-related trend for the incidence of C-cell adenoma of the thyroid in female rats (pooled controls 1/66, low-dose 1/49, high-dose 4/44, P=0.035). These endocrine tumors in female rats are believed to have been spontaneous, and not related to treatment. In mice, the incidences of polypoid carcinoma (adenocarcinoma in adenomatous polyp) of the duodenum were statistically significant using tests for a positive dose-related trend both in male mice (pooled controls 0/68, low-dose 1/43, high-dose 3/46, P=0.033) and in female mice (pooled controls 0/68, low-dose 0/49, high-dose 3/48, P=0.022). When the incidences of adenomatous polyp, NOS (not otherwise specified), were combined with those of polypoid carcinoma for statistical analysis, the tests for male mice indicated a substantial increase in significance (pooled controls 0/68, low-dose 3/43, high-dose 5/46, P=0.008). It is concluded that under the conditions of this bioassay, tumors in the duodenum of B6C3F1 mice were associated with treatment with captan, but there was no convincing evidence that the tumors observed in Osborne-Mendel rats were related to treatment.

Journal Article↗

Nonteratogenicity of captan in beagles.

Thirty and 60 mg/kg captan, administered in the diet during the entire gestation period or during gestation and an 8-week lactation period, caused no adverse effects in either mothers or progeny, and captan is thus judged to be nonteratogenic in beagles.

Animals↗

1,8-Naphthalic anhydride antidote enhances the toxic effects of captan and thiram fungicides on Azospirillum brasilense cells.

The effects of ten fungicides, six herbicides and four insecticides on the nitrogen-fixing bacterium Azospirillum brasilense were examined. The fungicides captan and thiram were the most toxic among the compounds tested. Cell growth and nitrogenase activity of the bacterium were markedly inhibited by low concentrations of the two fungicides. Antidote 1,8-naphthalic anhydride increased by a factor of 2 the cellular level of glutathione. The addition of the antidote in the presence of captan or thiram caused a similar increase in the glutathione content, but at the same time enhanced the toxicity of the two fungicides.

Azospirillum brasilense↗

Human intake fractions of pesticides via greenhouse tomato consumption: comparing model estimates with measurements for Captan.

Human intake due to pesticide residues in food commodities can be much higher than those related to water consumption and air inhalation, stressing the importance to correctly estimate pesticide uptake into plants and predict subsequent intake by humans. We calculated the human intake fraction of captan via tomato consumption taking into account the time between pesticide application and harvest, the time between harvest and consumption, the absorption of spray deposit on plant surfaces, transfer properties through the cuticle, degradation inside the plant and loss due to food processing. Human population intake fractions due to ingestion were calculated for complete, washed and peeled tomatoes. The calculated intake fractions were compared with measurements derived from an experimental setup in a Mediterranean greenhouse. The fraction of captan applied in the greenhouse as plant treatment that eventually is ingested by the human population is on average 10(-2)-10(-5), depending on the time between pesticide application and ingestion of tomatoes and the processing step considered. Model and experimentally derived intake fractions deviated less than a factor of 2 for complete and washed tomatoes and a factor of 3 for peeled tomatoes. Intake fractions due to air inhalation and consumption of drinking water are expected to be significantly lower (5-9 orders of magnitude) than those induced by the intake of tomatoes in this case study.

Captan↗

Evaluation of genotoxicity of captan, maneb and zineb in the wing spot test of Drosophila melanogaster: role of nitrosation.

The wing spot test in Drosophila melanogaster is a suitable system for the analysis of genotoxic activity of compounds that need metabolic transformation to render them active. We have analysed the genotoxicity of three fungicides for which it was reported that the metabolic processes taking place in vivo may determine their activity. The compounds analysed are captan, maneb, zineb and ethylenethiourea (ETU) (a metabolic derivative of ethylenebisdithiocarbamates like maneb and zineb). We have also evaluated the ability of ETU to form genotoxic derivatives in vivo analysing this compound in combined treatments with sodium nitrite. Both standard and high bioactivation NORR strains have been used. Captan, usually considered a mutagen in vitro but a non-mutagen in vivo, gave negative results in the wing spot test with both crosses. Positive results were obtained for maneb in the standard cross and for ETU in both the standard and the high bioactivation cross. The genotoxicities of maneb and ETU were higher when treatments were made on media in which nitrosation is favoured. A low absorption of the fungicide and an inefficient availability of the compound in the target may explain negative results obtained with zineb in both crosses. The results obtained in this study with the wing spot test demonstrate once again the suitability of this in vivo assay, in which absorption, distribution and metabolism processes take place, for the evaluation of genotoxicity of compounds to which humans are exposed.

Animals↗

Mutagenic and genotoxic activities of four pesticides: captan, foltaf, phosphamidon and furadan.

The mutagenic and genotoxic potential of four pesticides viz. captan, foltaf, phosphamidon and furadan was evaluated by the Ames mutagenicity assay and their DNA damaging ability on radiation repair defective E. coli K-12 strains respectively. The mutagenic spectrum revealed captan to be most mutagenic in the absence of metabolic activation, while the presence of S9 mix led to an attenuated mutagenic response. Foltaf, phosphamidon and furadan were detected as relatively weaker mutagens. A significant decrease in the survival of SOS defective mutants, recA, lexA and pol- of E. coli was observed as compared to their wild-type counterparts in the presence of the pesticides. The role of SOS repair genes gains further support from the Salmonella strains triggering the error-prone SOS response.

Captan↗

Determinants of exposure to captan in fruit growing.

A series of studies investigated occupational exposure to pesticides among fruit growers in The Netherlands during spraying and reentry of orchards between 1990 and 1992 to identify and quantify determinants of exposure. Determinants of exposure are discussed as a starting point for hazard identification and control. Captan was used as a marker for exposure. Cabin use of the tractor was the most prominent determinant of dermal exposure during spraying. For respiratory exposure, factors related to preparation of pesticides were most prominent. A long duration of exposure may reflect a different exposure situation compared with a short duration of exposure. As different determinants of exposure prevailed for each subgroup, consideration should be given to constructing exposure models for each group separately. Dislodgeable foliar residue (DFR) was the most prominent determinant of exposure for both respiratory and dermal exposure during reentry. However, no significant relation between DFR and dermal exposure of forehead and sternal area was found, perhaps because there was no direct contact with foliage here. Therefore, use of a transfer factor based on DFR to estimate total dermal exposure is only a crude estimate. The half-life of captan on crops varied from 10-17 days, so substantial exposure when entering the orchard is very likely, particularly when spraying frequency is high. The main starting points for reduction of exposure are use of a cabin, DFR, and individual time spent on different tasks. Determinants that are constant over time (cabin use) may have an especially great influence on grouping workers, according to long-term exposure in epidemiological studies. As determinants of exposure vary for the different exposure routes and body locations (for dermal exposure), the measure of interest for a specific study design will decide which determinants are most relevant.

Adult↗

Spectrophotometric determination of the fungicide captan.

A spectrophotometric method for the determination of the fungicide captan has been developed based on its reaction with thiosemicarbazide. The absorbance was measured at 315 nm. The effects of the proportion of water, thiosemicarbazide concentration, pH and temperature on this reaction was studied to select the best chemical conditions. The calibration graph was obtained between 1.2 and 30 ppm and the detection limit is 0.5 ppm. The RSD (n = 10) was 1.34%. Possible interference of various pesticides was examined. The method was applied to the determination of captan in agrochemical formulations. Results agree well with the labelled values and also with results that were obtained by a polarographic method.

Captan↗

Mutagenic evaluation of the pesticides captan, folpet, captafol, dichlofluanid and related compounds with the mutants TA102 and TA104 of Salmonella typhimurium.

A mutagenic evaluation of captan, folpet, captafol, dichlofluanid and related compounds was carried out using the Salmonella/mammalian microsome test using strains TA102 and TA104. These strains contain A-T base pairs at the site of the mutation in contrast to the other Salmonella tester strains that detect mutagens damaging G-C base pairs. In addition, the excision repair system of the TA102 strain is still intact. Captan and folpet were mutagenic in strain TA104, captafol was mutagenic in strain TA102, whereas the remaining test compounds (dichlofluanid, tetrahydrophthalimide and thiozolidine-4-carboxylic acid) were not mutagenic in either strain. In conclusion, we consider it of value to add these two strains to those already used in the Ames test in order to increase confidence in our ability to detect mutagens and to shed further light on their mechanism of action.

Aniline Compounds↗