Mutagenicity studies with captan, captofol, folpet and thalidomide

Kennedy, Gerald L.; Arnold, D.W.; Keplinger, M.L.

doi:10.1016/0015-6264(75)90082-6

Cited by 33 publications

(8 citation statements)

References 13 publications

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“…Similarly, rats dosed orally at 125 or 250 mg kg À 1 day À 1 for 14 days did not show a dominant lethal effect (Kennedy, Arnold, and Keplinger, 1975).…”

Section: Genetic Toxicologymentioning

confidence: 91%

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Toxicology of Fungicides

Ballantyne¹

2003

Pesticide Toxicology and International Regulation

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“…Similarly, rats dosed orally at 125 or 250 mg kg À 1 day À 1 for 14 days did not show a dominant lethal effect (Kennedy, Arnold, and Keplinger, 1975).…”

Section: Genetic Toxicologymentioning

confidence: 91%

“…Negative teratogenicity studies in rats, hamsters, rabbits, and dogs have also reported by Kennedy, Fanther, and Calandra (1968) and Kennedy, Arnold, and Keplinger (1975).…”

Section: Developmental Toxicitymentioning

confidence: 98%

Toxicology of Fungicides

Ballantyne¹

2003

Pesticide Toxicology and International Regulation

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“…In the vast majority of in vivo studies, neither captan nor folpet induce mutagenic events in intact animals (Litton Bionetics 1980;Brad eld 1980;Chidiac and Goldberg 1987;Epstein et al 1972;Esber 1983;Fry and Fiscor 1978;Jacoby 1985a;Jacoby 1985b;Jenssen and Ramel 1980;Jorgenson et al 1976;Kennedy et al 1975;Kramers and Knaap 1973;Mollet 1973;Mollet and Wurgler 1974;Moore 1981;Moore 1985;Rideg 1982;Simmon et al 1977;Tezuka et al 1978;Vogel and Chandler 1974). Some positive results have been reported.…”

Section: Table 11mentioning

confidence: 99%

An Evaluation of the Common Mechanism Approach to the Food Quality Protection Act: Captan and Four Related Fungicides, a Practical Example

Bernard

Gordon²

2000

Int J Toxicol

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Under the Food Quality Protection Act (FQPA) of 1996 (Act), the United States Environmental Protection Agency (EPA) is mandated to conduct cumulative risk assessment on pesticides that act through a common mechanism of toxicity. Incumbent on the Agency is the development of sound scientific principles upon which to evaluate compounds for the presence of a common mechanism. Using the currently available draft guidance criteria, this paper employs five fungicides of the same general class, typified by captan, to evaluate both the criteria and the available scientific data. Captan and folpet are two chloroalkylthio fungicides currently registered with EPA under Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) for agricultural use. As such, these compounds are subject to the provisions of FQPA. Three additional fungicidal compounds—dichlofluanid, tolylfluanid, and captafol—are not registered for use in the United States; however, these five compounds have chemical structure and biological toxicity similarities and differences that permit their utility as test cases to determine what the EPA would conclude, with regard to common mechanism, if these draft guidelines were applied to these compounds. The results of the analyses are consistent and support the conclusion that captan and folpet share a common mode of toxicity for mouse duodenal tumors as defined in the Act. This common mode of toxicity is not shared by dichlofluanid, tolylfluanid, or captafol. The basis for concluding a common mechanism exists between captan and folpet. They include 1. Structural Similarity—The compounds are structural analogs having the identical biologically active moiety (i.e., the-SCCl3 side chain). 2. Mechanisms of Pesticidal Action—The compounds have the same mechanism of action. The overwhelming body of evidence suggests they are active because of their reactions with thiols. Both compounds, in reacting with thiols, produce similar degradates. Differences in rates of reaction are attributable to physical-chemical properties of the two compounds. 3. General Mechanisms of Mammalian Toxicity—The compounds induce mammalian toxicity through the same mechanism that is responsible for their pesticidal action, reactions with thiols. Another, albeit less likely, mechanism (for both compounds) is cross-Unking of proteins with DNA, although the extremely short half-lives of these compounds (seconds) argues against this possibility. 4. Sites of Action—Both compounds express their primary toxicity as local rather than systemic effects. 5. Common Toxic Endpoint—These two compounds induce gastrointestinal tumors (in mice only). 6. Mode of Action—Both compounds express their common toxic endpoint through a nongenotoxic, compensatory proliferation mechanism. 7. Specificity of Action—For both compounds, the majority of tumors appear in the duodenum. Furthermore, these tumors are induced only in mice. Repeated carcinogenicity testing suggests that rats are refractive to the effects of captan and folpet. The significantly faster hydrolytic rate for folpet at the lower pH values (e.g., increased 8-fold at pH 5) encountered in the stomach is believed to account for the tumors of the stomach observed with folpet and not captan. 8. Other Toxic Endpoints—For other toxic endpoints where comparative data are available, captan and folpet show similar patterns of toxicity (e.g., mutagenicity, skin sensitization, and acute toxicity).

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“…It is also known as phthalimide, and it is essential for life. Isoindole‐1,3‐dione derivatives have attracted great deal of attention because of their important pharmaceutical properties such as antibacterial, antifungal, analgesic , antimicrobial , anti‐tumor , anxiolytic , hypoglycemic , antipsychotics , anti‐inflammatory , anticonvulsants , α‐glucosidase inhibitor , and anti‐HIV‐1 activity . Thiazole and 2‐aminothiazole derivatives are found in many natural products; therefore, they play an essential role in pharmacological applications.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Carbonic Anhydrase Inhibition of Novel 2‐(4‐(Aryl)thiazole‐2‐yl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7‐methanoisoindole‐1,3(2H)‐dione Derivatives

Koçyiğit

Aslan

Gülçın

et al. 2016

Archiv der Pharmazie

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Carbonic anhydrase (CA, EC 4.2.1.1) is a member of the metalloenzyme family. It catalyzes the rapid conversion of carbon dioxide (CO ) and water to bicarbonate (HCO ) and protons (H ) and also plays an important role in biochemical and physiological processes. In this study, a number of novel 2-(4-(aryl)thiazole-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives were synthesized and evaluated for their inhibitory characteristics against the human CA isoenzymes I and II (hCA I and hCA II). The structures of the new molecules 8a-i were confirmed by means of IR, H NMR, C NMR, and elemental analysis. These compounds exhibited excellent inhibitory effects, in the low nanomolar range, with K values in the range of 27.07-37.80 nM against hCA I and in the range of 11.80-25.81 nM against hCA II. Our findings suggest that the new isoindolylthiazole derivatives have superior inhibitory effect over acetazolamide (AZA), which is used as clinical CA inhibitor with K values of 34.50 and 28.93 nM against the hCA I and hCA II isoenzymes, respectively.

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Mutagenicity studies with captan, captofol, folpet and thalidomide

Cited by 33 publications

References 13 publications

Toxicology of Fungicides

Toxicology of Fungicides

An Evaluation of the Common Mechanism Approach to the Food Quality Protection Act: Captan and Four Related Fungicides, a Practical Example

Synthesis and Carbonic Anhydrase Inhibition of Novel 2‐(4‐(Aryl)thiazole‐2‐yl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7‐methanoisoindole‐1,3(2H)‐dione Derivatives

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