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At least 19 recordsLinked to original sources

PubMed1976

Experimental and field studies with thiophanate in pigs.

Thiophanate, administered at a dosage of 50 mg per kg to artifically infected pigs, removed 96 to 99 per cent of adult Oesophagostomum spp, Hyostrongylus rubidus and Trichuris suis. Activity was also high against larval stages of these nematodes, except for 26-day-old T suis. Thiophanate also showed ovicidal and larvicidal activity against H rubidus and Oesophagostomum spp. At 50 mg per kg thiophanate administered alone was inactive against Ascaris suum and Metastrongylus apri, the former species also being refractory at 200 mg per kg. Field trials confirmed these efficacy results in naturally infected animals. Pellet formulations providing mean dosages of 63 mg thiophanate per kg for adult pigs and 75 mg thiophanate per kg with 83 mg piperazine base per kg for growing pigs were highly effective in reducing the faecal output of Oesophagostomum spp, H rubidus and T suis eggs. In growing pigs, A suum was controlled by the thiophanate/piperazine product. No palatability or tolerance problems were observed when thiophanate or thiophanate/piperazine mixtures were administered at recommended dosage or multiples thereof in experimental or field studies.

Animals↗

PubMed1999

Flow cytometric analysis of genetic damage, effect on cell cycle progression, and apoptosis by thiophanate-methyl in human lymphocytes.

Flow cytometric technique was used to study the effects of the fungicide Thiophanate-methyl on cell proliferation, micronucleus induction, and apoptosis in human peripheral blood lymphocytes treated in vitro. In particular, a combined approach of flow cytometry and fluorescence in situ hybridization (FISH) with a pancentromeric alpha-satellite probe was used to evaluate the mechanism of micronucleus induction by Thiophanate-methyl. Flow sorted micronuclei (MN) induced in human lymphocytes by Thiophanate-methyl were analyzed by FISH and the results were compared with results from FISH analysis on MN in binucleated cells. It could be shown that most MN induced by Thiophanate-methyl did not reveal any centromeric signal, thus demonstrating clastogenic action of this fungicide. Moreover, it was found that as a function of the concentration of Thiophanate-methyl, cellular proliferation was delayed and the frequency of apoptotic cells was increased.

Adult↗

PubMed1990

Critical controlled test to evaluate resistance of field strains of Haemonchus contortus to thiophanate.

Following reports of suspected gastrointestinal strongylid nematode resistance to thiophanate in sheep and goats at Sokoine University of Agriculture (SUA), Tanzania, field strains of Haemonchus contortus, one from SUA and another from Kimamba, Tanzania, were selected for a critical controlled test to evaluate the efficacy of thiophanate. The SUA H. contortus strain in goats showed a marked resistance to thiophanate at an oral dose of 50 mg kg-1 liveweight (efficacy = 24.1%), while the Kimamba H. contortus strain showed very marked susceptibility (efficacy = 99.7%) to thiophanate at the same oral dose. This is the first report from East Africa of a field strain of H. contortus resistant to thiophanate. The incidence of resistant strains of strongyloid parasites to benzimidazole anthelmintics in sheep and goats in East Africa is on the increase. The magnitude of this problem should be evaluated and remedial solutions sought.

Abomasum↗

PubMed2006

The newt Triturus carnifex as a model for monitoring the ecotoxic impact of the fungicide thiophanate methyl: adverse effects on the adrenal gland.

The aims of this study were to propose a bioindicator organism, the newt Triturus carnifex, for the assessment of toxicological impact of thiophanate methyl in the Campania region (Italy) and the possible adverse activity on the adrenal gland. In the acute toxicity study, experimental groups of T. carnifex were exposed to 2.40, 4.80, 9.60 and 19.20 microg/L tap water of thiophanate methyl for 2 days; the LD50 was found to be 9.60 microg/L. To evaluate the effects on the adrenal gland, newts were exposed to a dose of 25% of the LD50 2 days for 8 days. The ultrastructural features of the tissues as well as the serum levels of aldosterone, corticosterone, norepinephrine (NE) and epinephrine (E) were evaluated. The number of secretory vesicles in the chromaffin cells appeared significantly decreased, whereas NE and E serum levels appeared strongly increased. Moreover, corticosterone and aldosterone serum levels appeared significantly reduced. The results suggest that: 1) T. carnifex has the features of an ideal bioindicator, due to its high sensitivity to thiophanate methyl, 2) thiophanate methyl acts as endocrine disruptor, affecting the adrenal gland at very low doses, 3) thiophanate methyl may be toxic for nontarget organisms, such as newts.

Adrenal Glands↗

PubMed1980

Resistance of Haemonchus contortus to thiophanate.

The occurrence of a field strain of Haemonchus contortus which was resistant to thiophanate and susceptible to thiabendazole and levamisole is reported. The LD95 of thiophanate for the strain was found to be 156.1 mg/kg and its resistance factor was 6.7. In possessing specific thiophanate resistance it differed from previously reported thiophanate resistant strains of H contortus which have been benzimidazole resistant worms that have possessed cross resistance to thiophanate.

Animals↗

PubMed1977

Field trials in sheep with the anthelmintic thiophanate.

Productivity and tolerance trials were conducted with the anthelmintic thiophanate (Nemafax; May & Baker) in sheep in the United Kingdom. Tolerance studies, conducted in sheep of various types under several management systems, in which thiophanate was given orally at recommended dosage (50 to 100 mg/kg), or multiples thereof, in single or repeated doses showed that treatment was in all cases well tolerated. Thiophanate administered at 75 mg per kg or 250 mg per kg to groups of growing lambs with low faecal egg counts produced no post treatment depression of weight gain. When breeding ewes were treated with thiophanate at 150 mg per kg on days 14, 21 and 28 after introduction of rams to the flock, the anthelmintic produced no adverse effect on lambing performance. Trials to assess the beneficial effects of treatment were conducted in weaned lambs naturally infected with gastrointestinal nematodes. Groups of lambs were treated monthly with either thiophanate or tetramisole at recommended dosages. The two anthelmintics produced similar weight gains in the lambs and these were significantly better than those of untreated controls. In untreated controls faecal egg counts increased markedly and the clinical condition of these animals deteriorated.

Administration, Oral↗

PubMed1996

Comparative efficacies of closantel, ivermectin, oxfendazole, thiophanate and levamisole against thiabendazole resistant Haemonchus contortus in sheep.

Forty-nine sheep artificially exposed to a thiabendazole (TBZ) resistant isolate of Haemonchus contortus were assigned to 7 groups of 7 animals each and used to conduct a controlled anthelmintic trial. One group of sheep served as untreated infected controls and 6 groups were treated as follows: closantel, 5.0 mg kg-1; ivermectin, 0.2 mg kg-1; oxfendazole, 5.0 mg kg-1; thiophanate, 50 mg kg-1, levamisole, 7.5 mgkg-1 and thiabendazole, 66 mg kg-1. Eggs per gram of faeces were determined on days 21, 24 and day 34 (10 days post-treatment) after infection and all animals were necropsied for residual worm counts. The calculated efficacies of the treatments against H. contortus as indicated by worm reduction were closantel (100%), ivermectin (99.3%), oxfendazole (35.2%), thiophanate (56.7%), levamisole (98.6%) and thiabendazole (24.3%). The data therefore indicate that the TBZ-resistant isolate of H. contortus used was highly resistant to the 2 benzimidazole (BZ) anthelmintics, oxfendazole and thiophanate. This is the first report in Kenya of a field strain of H. contortus resistant to thiophanate.

Animals↗

PubMed1978

Thiophanate as a low daily dosage anthelmintic in sheep.

Thiophanate administered daily at low dosages reduced nematode faecal egg output, egg hatchability and parasitic worm burdens in treated lambs and ewes. Six daily doses of 1 or 3 mg per kg thiophanate (approximately 1/25th to 1/75th of the median therapeutic dose), given to lambs experimently infected with Trichostrongylus colubriformis, were partially effective in suppressing faecal egg output and egg hatchability. Six doses of 5 mg per kg per day were effective in lambs infected with Haemonchus contortus and Nematodirus spathiger. Daily doses of thiophanate (50 or 200 mg per head) given over 14 weeks to lambs grazing contaminated pasture resulted in improved productivity (the higher dosage) and suppression of output of viable eggs and reduced worm burdens (both dosages). Reduced output of viable eggs was also obtained in housed, lactating ewes receiving 5 or 7 mg per kg thiophanate dispersed daily in the feed for 11 or nine weeks respectively after lambing.

Animals↗

PubMed1990

Efficacy of thiophanate and albendazole against natural infections of Dicrocoelium dentriticum, Fasciola hepatica, and gastrointestinal nematodes and cestodes in sheep.

The anthelmintic efficacy of thiophanate and albendazole was compared in sheep with heavy infestations of Dicrocoelium dentriticum. The effectiveness of each drug was determined by counting the numbers of D. dentriticum in animals killed 21 days after treatment. In one group, the dose of thiophanate recommended for use against gastrointestinal (GI) nematodes (50 mg kg-1 live weight) was found to be 74.4% effective against D. dentriticum. Two tablets (each containing 76 mg of active ingredient) of albendazole per 30 kg live weight were given to a second group and the dose repeated after 1 week. Under this regime, albendazole was found to be 12.7% effective against D. dentriticum. The effect of each drug on other parasites was as follows; thiophanate had no effect against Fasciola hepatica or cestodes, while albendazole was 71.5% effective against F. hepatica and 100% effective against cestodes. Both drugs were highly effective against GI nematodes.

Albendazole↗

PubMed1990

[Ethyl benzimidazole carbamate: teratogenic effect and presence in the milk of cows after administration of thiophanate].

After oral administration of 40 mg/kg of thiophanate to dairy cows, the active metabolite, ethyl-1H-benzimidazol-2-yl carbamate (EBC) reached a maximal concentration of 0.44 microgram/ml during the first milking and was eliminated by the mammary gland after 60 h. BCE is teratogenic in rats at doses of over 6.8 mg/kg while thiophanate at doses of up to 148 mg/kg is not. These results indicate that thiophanate treatment for dairy cattle may be questionable.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

The effect of continuous in-feed medication with thiophanate on Ascaris suum and Oesophagostomum spp. egg output in young pigs.

The full potential of anthelmintics now available for single dose treatment is not achieved because the devising system for worm control in piglets/weaners is not efficiently applicable in practice. Therefore an in-feed medication programme for growing young pigs, allowing only one feed lot to be handled by the farmer, was tested in two studies. Study A Feed containing 0.0225% thiophanate was continuously fed almost ad lib. to piglets from birth right up to about 25 kg body weight when ready for fattening. This control measure effectively prevented A. suum and Oesophagostomum from becoming established during the whole pre-fattening period, thus allowing "worm-free" weaners to be produced. -33% of animals receiving unmedicated feed harboured mature Oesophagostomum already at an age of 63 days when first examined. Three out of 97 unmedicated pigs were then A. suum egg-count positive. At the same time all medicated pigs, except one with a low Oesophagostomum egg output, were egg-count negative. All medicated were still egg-count negative at 23-29 days after the withdrawal of the feed. About 30% of unmedicated pigs were then shedding eggs of A. suum and Oesophagostomum respectively. At 45-49 days after the withdrawal of the medicated feed 8% of previously medicated pigs and 43% of unmedicated pigs were A. suum egg-count positive. The corresponding figures for Oesophagostomum egg-count positive pigs were 6% and 40% respectively. The acquisition of worm infections by previously medicated pigs most probably was made in the fattening unit after the withdrawal of the thiophanate medicated feed. Study B In this study it was further substantiated that in-feed medication of pigs with thiophanate prevents A. suum from becoming established. All treated pigs were A. suum egg-count negative at Day 43 and 46 after the withdrawal of the medicated feed whereas about 62% of untreated control pigs were shedding A. suum eggs at the same time. This finding justify the proposal that the in-feed medication performed prevented larval migration. Furthermore it was shown that the in-feed medication must proceed right up to the transfer of piglets to the fattening unit in order to achieve its full potential. Farrowing pens may be heavily contaminated with infective Oesophagostomum larvae at the end of the pre-fattening period resulting in sudden and heavy nodular worm infections after the withdrawal of the medicated feed.

Animal Feed↗

PubMed1997

Cytotoxic and cell transforming activities of the fungicide methyl thiophanate on BALB/c 3T3 cells in vitro.

Cytotoxic and cell-transforming activities of methyl thiophanate a systemic fungicide capable of entering plant cells and thus controlling fungal diseases that have already started were studied in an in vitro medium-term (6-8 weeks) experimental model utilizing BALB/c 3T3 cells. Cells were exposed to the chemical, dissolved in dimethyl sulfoxide, in the absence or presence of an exogenous metabolizing system derived from rat livers supplemented with cofactors (S9 mix). In the absence of metabolic activation, methyl thiophanate exerted cytotoxic activity, evidenced through the formation of cell colonies, at low doses (> 10 micrograms/ml). However, the cytotoxic activity was greatly reduced by the S9 mix-induced metabolic activation of the chemical. Without bioactivation, cell-transforming potential, evidenced through the induction of transformation foci, was observable only at the highest (weakly toxic) dose employed (25 micrograms/ml). On the contrary, in the presence of metabolic activation, the cell-transforming activity was detectable at all tested doses (i.e. from 20 to 200 micrograms/ml) and it was particularly evident in a level-II transformation amplification test when the cells were allowed to perform active proliferative activity. These results, providing further information on the activity of methyl thiophanate in multistep carcinogenesis as possible genotoxic and/or co-carcinogenic agent, may contribute to better evaluate the oncogenic risk to man.

3T3 Cells↗

PubMed1984

Field studies with in-feed medication of pigs in the Netherlands using the anthelmintic thiophanate with particular reference to efficacy against Ascaris suum.

Studies on the efficacy in pigs of low level in-feed medication with the anthelmintic thiophanate at a minimum intake of 6 mg/kg/day for fourteen days are reported. A trial was conducted to compare a group of medicated fattening pigs with a similar unmedicated group on premises known to have a high challenge of Ascaris spp. Daily growth rate was improved whilst feed conversion ratio and the liver condemnation rate were reduced in the treatment group. Routine medication of a whole herd using this regime contributed to a great improvement of the herd production when assessed by the above criteria. User studies in various geographical areas of the Netherlands involving 1500 adult pigs and 1200 fattening pigs medicated with thiophanate in-feed for fourteen days demonstrated that the compound eliminated the faecal worm egg output and was readily accepted and tolerated by pigs.

Animal Feed↗

PubMedDate not supplied

A simple and rapid spectrophotometric method for determination of thiophanate-methyl in commercial formulations and its residues in foodstuffs.

A new, simple, rapid, and sensitive spectrophotometric method for the determination of thiophanate-methyl, based on its reaction with cobalt(II) in the presence of triethylamine, has been developed. The yellowish green color that develops instantaneously on mixing the fungicide with the reagents in dimethylformamide is stable for at least 2 h and has maximum absorbance at 360 nm. The method has been successfully applied to the determination of thiophanate-methyl in its commercial formulations and residues on grains and apples. A photometric titration procedure for formulation analysis of the fungicide has also been developed.

Colorimetry↗

PubMedDate not supplied

Effect of benomyl and thiophanate-methyl on metabolic activities of Rhizoctonia solani Kühn.

Effect of benomyl and thiophanate-methyl on various metabolic activities of Rhizoctonia solani was investigated. Both fungitoxicants strongly reduced endogenous whole cell and mitochondrial respiration by inhibiting one or the other key enzymes of electron transport chain; the activity of cytochrome oxidase being most markedly inhibited. Incorporation of 3II-thymidine was reduced by both while there was little or no inhibition in the rate of incorporation of 14C-uracil and 14C-leucine. Cell permeability was not affected to any appreciable extent and there was a little release of cellular components from the treated cells only at prolonged incubation. It is concluded that benomyl and thiophanate-methyl have a similar mode of action which primarily involves inhibition of respiratory activities, and as a consequence the biosynthesis of DNA is reduced.

Benomyl↗

PubMed1988

[Pharmacokinetics and anti-Dicrocoelium activity of thiophanate and its major metabolite in ruminants].

After a single oral dosage of 40 mg thiophanate/kg in cattle, sheep and goats, the parent compound and its main metabolite: ethyl benzimidazol-1H-yl-2-carbamate (EBC) are evidenced in plasma by HPLC analysis for 60 to 72 hours. The rate of metabolic change of thiophanate into EBC is 34% in sheep, 52% in goats and 57% in cattle. At this dosage, thiophanate seems to be effective against Dicrocoelium in sheep. On the contrary, EBC is uneffective at 15 mg/kg while it seems undetectable in plasma at any time.

Animals↗

PubMed1985

A strain of Haemonchus contortus resistant to thiophanate.

The occurrence of a field strain of Haemonchus contortus resistant to thiophanate is reported for the first time in New Zealand. In a controlled anthelmintic trial with experimentally infected animals, thiophanate at 50-100 mg/kg had no appreciable effect on the Haemonchus burden. Albendazole reduced faecal strongylate egg counts by 95% in animals with naturally acquired 59 infections.

Journal Article↗

PubMedDate not supplied

In vivo studies on possible adverse effects on reproduction of the fungicide methyl thiophanate.

The fungicide methyl thiophanate (MT), widely used to control some of the most common fungal diseases in crops, is metabolized in animals into benzimidazole compounds, including the well-known reproductive toxicant carbendazim. However, standard toxicological tests did not indicate that MT may cause testicular toxicity and/or embryotoxicity, which are typical effects of many benzimidazoles. In the present study some aspects of the MT potential for reproductive toxicity have been assayed by means of two non-conventional models. Following the oral administration of 700 and 1000 mg kg(-1) body wt. for five consecutive days, short-term testicular toxicity was examined in the B6C3F1 mouse through specific parameters (sperm head count, specific enzyme activities, histopathology on days 3-35 post-dosing). In spite of the high doses administered, none of the testicular parameters examined, including histopathology, showed significant alterations as compared to controls at any time post-dosing. Pregnant CD rat dams were administered orally the limit dose of 650 mg kg(-1) body wt. day(-1) during preimplantation (gestational day or GD 2-5) or peri-implantation (GD 6-9) phases; embryos and adnexa were evaluated morphologically on GD 12 as a window for the early observation of embryotoxicity. Evident maternal toxicity was present in both treated groups, whereas only marginal reductions of the growth of embryos and adnexa were observed. A full understanding of MT toxicology will need more quantitative data on metabolism, including plasma kinetics and dosimetry of carbendazim at the relevant targets. Nevertheless, the absence of any clear-cut effect on a number of specific endpoints may provide reassurance that no further testing of MT is needed with regard to testicular toxicity or embryotoxicity.

Administration, Oral↗