Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Di-(2-ethylhexyl)phthalate (DEHP) produced hepatocellular carcinomas in rodents at high doses in a NTP/NCI bioassay. DEHP has not shown evidence of genotoxic activity in in vitro mutagenicity tests. We extended these studies by examining the mutagenicity of urine from rats dosed with DEHP, 2-ethylhexanol (2-EH), and several other 2-EH derived plasticizers, i.e. di-(2-ethylhexyl)adipate (DEHA), di-(2-ethylhexyl)terephthalate (DEHT) and tri-(2-ethylhexyl)trimellitate (TEHT). A modified Ames Salmonella/microsome assay was used to determine mutagenicity. Urine was pooled from male Sprague--Dawley rats dosed daily for 15 days with 2000 mg/kg of each test substance with the exception of 2-EH which was given at 1000 mg/kg. Direct plating procedures were used to determine the presence of mutagens in urine. Urine from rats dosed with 8-hydroxyquinoline was used as a positive control. There was no evidence that mutagenic substances were excreted in the urine by rats dosed with either DEHP, DEHA, DEHT, TEHT or 2-EH as determined in the presence or absence of rat liver microsomes, and with or without treatment with beta-glucuronidase/aryl sulfatase. Our findings indicate that the above test compounds were not converted to urinary metabolites that were mutagenic. These observations provide no evidence for a genotoxic mechanism for DEHP carcinogenicity in rodents.
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PMID:Bacterial mutagenicity testing of urine from rats dosed with 2-ethylhexanol derived plasticizers. 388 74

Di(2-ethylhexyl)phthalate (DEHP) is extensively used as a plasticizer for vinyl plastic articles. It has been found to be positive in an NCI rodent bioassay but has generally given negative results in in vitro genotoxicity tests. We therefore decided to test the urine of rats fed [14C]DEHP for mutagenic activity in the Ames Salmonella test. The recovery of radioactivity from the urine of rats dosed with [14C]DEHP was examined by solvent extraction and XAD-2 resin absorption procedures. Both of these procedures were inadequate for quantitative recovery of urinary metabolites required for subsequent mutagenicity testing using the Ames Salmonella/microsome procedure. Recoveries of less than 5% were observed using standard solvent extraction techniques whereas the XAD-2 adsorption technique gave about 67% at high resin/urine ratios. Treatment of the urine with beta-glucuronidase/aryl sulfatase did not affect these recoveries. The direct urine plating procedure represents a viable alternative to the above concentration procedures for this phthalate ester. The effects of L-histidine and the beta-glucuronidase/aryl sulfatase preparation on the background reversion frequencies of the Ames tester strains is discussed.
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PMID:Methods for measuring mutagenicity in urine of rats dosed with [14C]di(2-ethylhexyl)phthalate. 397 21

Di(2-ethylhexyl) terephthalate (DEHT) is a commercially produced chemical (Kodaflex DOTP) that is used as a general purpose, low-volatility plasticizer for polyvinyl chloride and other polymeric materials. Less than 30 million kilograms of DEHT are produced annually. DEHT is isomeric with di(2-ethylhexyl) phthalate (DEHP), a nongenotoxic rodent carcinogen whose mode of action has been suggested to derive from its ability to produce hepatocellular proliferation and/or hepatic peroxisome proliferation. Thus it is important to know the behavior of DEHT in genotoxicity assays in order to compare it with that of DEHP and other phthalate ester plasticizers. It is known from previously published studies that rats fed DEHT in the diet at 2,000 mg/kg produce urine that is negative in the Ames Salmonella bacterial mutagenicity assay in the presence and absence of induced rat liver S-9 and in the presence and absence of beta-glucuronidase/aryl sulfatase. Reported here are the results of direct testing of DEHT in the Ames plate incorporation assay, the Chinese hamster ovary/hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT) in vitro mammalian cell mutagenicity assay, and an in vitro chromosome aberrations assay using CHO cells. The results for mono(ethylhexyl) terephthalate (MEHT), a metabolite of DEHT, in the Ames Salmonella bacterial mutagenicity assay are also presented. All test results for both DEHT and MEHT were found to be negative, and it is therefore concluded that DEHT, like its isomeric relative DEHP, is not genotoxic.
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PMID:Genetic toxicology testing of di(2-ethylhexyl) terephthalate. 816 97