ABSTRACT
Di-n-butyl phthalate (DBP) is a ubiquitous environmental pollutant, extensively used as a softener for polyvinyl chloride resins. A study was conducted to evaluate its effect on reproductive function of Wistar rats. DBP was given orally at a dose of 500, 1000 and 1500 mg kg(-1) body weight for 7 days. Evaluating histological and fertility parameters assessed reproductive function. Significant reduction in seminiferous tubule diameter, Leydig cell nuclear diameter (except at dose 500 mg), number of primary spermatocytes, secondary spermatocytes and spermatids were observed. Caudal sperm density and viability reduced significantly. Decrease in serum testosterone was also observed. Evidence indicates that DBP exposure causes dose dependent testicular toxicity and has the potential to induce adverse effect.
Subject(s)
Animals , Cell Nucleus/drug effects , Dibutyl Phthalate/toxicity , Fertility/drug effects , Homeostasis/drug effects , Kinetics , Leydig Cells/drug effects , Male , Rats , Rats, Wistar , Seminiferous Tubules/drug effects , Spermatozoa/drug effects , Testis/drug effects , Toxicity TestsABSTRACT
Potential toxicological interactions of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibuthyl phthalate (DBP) on ozone were investigated after 32- and 52-wk exposures using hprt mutation assay. Male and female B6C3F1 mice exposed to ozone (0.5 ppm), NNK (1.0 mg/kg), DBP (5,000 ppm), and two or three combinations of these toxicants 6 h per day for 32- and 52-wk showed increases in the frequencies of TG rlymphocytes compared to the control groups. Additive interactions were noted from two combination groups compared to the ozone alone in both sexes of 32- and 52-wk studies. The most common specific mutation type in the hprt genes of test materials-treated male and female mice was transversion with very few transition. The results indicate that such dominant transversion may be responsible for toxicity and combined exposure to ozone, NNK, and DBP induces additive genotoxicities compared to ozone alone.
Subject(s)
Animals , Female , Male , Mice , Carcinogens/toxicity , DNA Mutational Analysis , Dibutyl Phthalate/toxicity , Drug Combinations , Hypoxanthine Phosphoribosyltransferase/genetics , Mutagenicity Tests , Mutation/drug effects , Nitrosamines/toxicity , Ozone/toxicity , Reverse Transcriptase Polymerase Chain Reaction , T-Lymphocytes/drug effectsABSTRACT
Toxic effects of ozone, 4-(N-methyl-N-nitrosamino)-1-(3- pyridyl)-1-butanone (NNK), and/or dibutyl phthalate (DBP) were examined through NF-kappaB, AP-1, Nrf2, and osteopontin (OPN) in lungs and livers of B6C3F1 mice. Electrophoretic mobility shift assay (EMSA) indicated that mice treated with combination of toxicants induced high NF-kappaB activities. Expression levels of p105, p65, and p50 proteins increased in all treated mice, whereas IkB activity was inhibited in NNK-, DBP-, and combination-treated ones. All treated mice except ozone-treated one showed high AP-1 binding activities. Expression levels of c-fos, c-jun, junB, jun D, Nrf2, and OPN proteins increased in all treated mice. Additive interactions were frequently noted from two-toxicant combination mice compared to ozone-treated one. These results indicate treatment of mixture of toxicants increased toxicity through NF-kappaB, AP-1, Nrf2, and OPN. Our data could be applied to the elucidation of mechanism as well as the risk assessment of mixture-induced toxicity.
Subject(s)
Animals , Mice , Blotting, Western , DNA-Binding Proteins/metabolism , Dibutyl Phthalate/toxicity , Electrophoretic Mobility Shift Assay , Kidney/drug effects , Liver/drug effects , Mice, Inbred Strains , NF-E2-Related Factor 2 , NF-kappa B/metabolism , Nitrosamines/toxicity , Osteopontin , Ozone/toxicity , Proto-Oncogene Proteins/metabolism , Risk Assessment , Sialoglycoproteins/metabolism , Trans-Activators/metabolism , Transcription Factor AP-1/metabolismABSTRACT
Di-n-butyl phthalate (DBP) was administered to adult male rats by gavage at the doses of 250, 500 and 1000 mg/kg body weight/day for 15 days. A significant decrease in epididymal spermatozoa counts was observed at 500 and 1000 mg/kg doses of DBP. The activity of sorbitol dehydrogenase was found to be significantly decreased while that of lactate dehydrogenase, gamma-glutamyl transpeptidase, beta-glucuronidase, and glucose-6-phosphate dehydrogenase, significantly increased in the animals exposed to 500 and 1000 mg/kg of DBP. Decrease in the activity of acid phosphatase was also observed at all dose levels. Histopathological studies revealed marked degeneration of seminiferous tubules, further confirming testicular toxicity of DBP. The results suggest that testicular atrophy caused by DBP is associated with an alteration in the activities of enzymes related with specific events of spermatogenesis.