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PubMed1997

An approach for modeling noncancer dose responses with an emphasis on uncertainty.

This paper presents an approach for characterizing the probability of adverse effects occurring in a population exposed to dose rates in excess of the Reference Dose (RfD). The approach uses a linear threshold (hockey stick) model of response and is based on the current system of uncertainty factors used in setting RfDs. The approach requires generally available toxicological estimates such as No-Observed-Adverse-Effect Levels (NOAELs) or Benchmark Doses and doses at which adverse effects are observed in 50% of the test animals (ED50s). In this approach, Monte Carlo analysis is used to characterize the uncertainty in the dose response slope based on the range and magnitude of the key sources of uncertainty in setting protective doses. The method does not require information on the shape of the dose response curve for specific chemicals, but is amenable to the inclusion of such data. The approach is applied to four compounds to produce estimates of response rates for dose rates greater than the RfD.

Acetamides↗
PubMedDate not supplied

Genotoxic effects of linear alkyl benzene sulfonate, sodium pentachlorophenate and dichromate on Tetrahymena pyriformis.

DNA in macro- and micronuclei of Tetrahymena pyriformis treated with linear alkyl benzene sulfonate (LAS) and sodium pentachlorophenate (PCP-Na) were determined by microspectrophotometry. The effects on rate of formation of macronuclear DNA extrusion bodies were also studied. We found DNA content of micronuclei in 0.14 ppm LAS and 0.9 ppb PCP-Na was lower than in that of the control, and LAS was able to increase the formation rate of macronuclear DNA extrusion bodies (the formation rate was 54% in 11.3 ppm LAS and 25.6% in 16.7 ppm dichromate). We concluded that 0.14 ppm LAS (below the maximum acceptable toxicant concentration) was genotoxic, whereas 0.014 ppm LAS was not. Dichromate 0.05 ppm and 0.9 ppb PCP-Na, equal to and below the maximum acceptable toxicant concentration, respectively, were potentially genotoxic.

Alkanesulfonates↗
PubMed1984

Disposition of some sulphur-containing hexachlorobenzene (HCB) metabolites: affinity of methylsulphonylpentachlorobenzene for the gray matter of brain, the lungs and the adrenal zona reticularis.

The distribution of methylsulphonylpentachloro-[14C]benzene (I), methylthiopentachloro-[14C]benzene (II), 1,4-bis(methylthio)tetrachloro-[14C]benzene (III) and 1,2,4-tris(methylthio)trichloro[14C]benzene (IV) was studied after intravenous injection in mice. The administration of I resulted in a rapid and selective accumulation of radioactivity in the gray matter of the brain, the lung and the zona reticularis of the adrenal cortex. In mice pretreated with metyrapone, or with high dose of unlabelled I, the radioactivity in the tissues was increased, whereas pretreatment with diethyl maleate did not change the disposition of I. In mice injected with II-IV no site of selective accumulation in the tissues was observed. Similarly to I, compounds II-IV were rapidly excreted in bile/faeces and urine. It is proposed that the sulphone group is essential for the high affinity of I for the brain, lung and adrenal cortex.

Adrenal Cortex↗
PubMed2005

The decrease in level of serum thyroxine by 2,2',4,5,5'-pentachlorobiphenyl in rats and mice: no correlation with formation of methylsulfonyl metabolites.

A relationship between formation of methylsulfonyl (MeSO2) metabolites of 2,2',4,5,5'-pentachlorobiphenyl (PentaCB) and decrease in serum thyroxine (T4) level was examined in the rats and mice after a single i.p. injection of PentaCB (342 micromol/kg body weight). In either rats or mice, levels of the 3- and 4-MeSO2 metabolites of PentaCB in the liver and feces increased in a time-dependent fashion up to 8 days after PentaCB-treatment. However, there was a marked difference between rats and mice in the amount of the metabolites formed, and the cumulative amount of the either MeSO2 metabolite for 8 days after PentaCB treatment in the liver was 4 to 15 times higher in mice than in rats. On the other hand, a 40 to 60% decrease in level of serum total T4 occurred in both rats and mice at 1 day after PentaCB treatment, and the decrease was retained up to 8 days after PentaCB treatment. Thus, there was a marked difference between rats and mice in the formation of MeSO2 metabolites from PentaCB but not a significant difference between rats and mice in PentaCB-induced decrease in the level of serum total T4, indicating that PentaCB-induced decrease in the level of serum total T4 is not necessarily dependent on the MeSO2 metabolites formed.

Animals↗
PubMed1982

Failure of Legionella pneumophila sensitivities to predict culture results from disinfectant-treated air-conditioning cooling towers.

The disinfection of cooling towers based on manufacturers' treatment protocols, as employed in units installed at various public gathering places in Dallas, Tex. (hotels, municipal auditorium), and at the city health department, was evaluated for effectiveness in controlling Legionella pneumophila and compared with previous laboratory studies. In specimens collected in September and December, 1978, L. pneumophila was isolated from 2 of 4 specimens from untreated cooling towers, 2 of 4 specimens from towers treated with agents deemed ineffective in earlier laboratory tests, 6 of 11 specimens from towers treated with putatively effective agents, and 0 of 4 specimens from towers treated with an agent unknown efficacy. These results suggest the need for further studies to identify biocidal agents effective in eliminating L. pneumophila from air-conditioning cooling towers.

Air Conditioning↗
PubMed1995

Quantitation of fungal mRNAs in complex substrates by reverse transcription PCR and its application to Phanerochaete chrysosporium-colonized soil.

Thorough analysis of fungi in complex substrates has been hampered by inadequate experimental tools for assessing physiological activity and estimating biomass. We report a method for the quantitative assessment of specific fungal mRNAs in soil. The method was applied to complex gene families of Phanerochaete chrysosporium, a white-rot fungus widely used in studies of organopollutant degradation. Among the genes implicated in pollutant degradation, two closely related lignin peroxidase transcripts were detected in soil. The pattern of lignin peroxidase gene expression was unexpected; certain transcripts abundant in defined cultures were not detected in soil cultures. Transcripts encoding cellobiohydrolases and beta-tubulin were also detected. The method will aid in defining the roles of specific genes in complex biological processes such as organopollutant degradation, developing strategies for strain improvement, and identifying specific fungi in environmental samples.

Base Sequence↗
PubMed1982

Pesticide poisoning of livestock: a review of cases investigated.

The cases of suspected poisoning of livestock by a range of organic chemicals, mainly pesticides, investigated at the Central Veterinary Laboratory during the period 1977 to 1980 are reviewed. The incidences of poisoning by various types of compound and the species most at risk are discussed. Organophosphorus pesticides and rodenticides were the commonest causes of poisoning. Pesticides accounted for one in 25 of all fatal poisonings listed by the veterinary investigation diagnosis analysis (VIDA) of the Ministry of Agriculture, Fisheries and Food.

Acetaldehyde↗
PubMed1979

Mannose transport in Amphora coffeaeformis var. perpusilla (Bacillariophyceae).

Amphora coffeaeformis var. perpusilla is able to concentrate but not metabolize mannose. The sugar, which can be accumulated against a concentration gradient, is taken up only after a short lag. Preincubation with glucose allows immediate mannose uptake. Substances that reduce the ATP content of the diatom cells also inhibit mannose uptake as do sugars of similar stereochemical configuration. Mannose appears to act as a non-metabolizable analogue of glucose in these respects.

Adenosine Triphosphate↗
PubMed2006

Effects of site-directed mutations in Escherichia coli succinate dehydrogenase on the enzyme activity and production of superoxide radicals.

Escherichia coli succinate dehydrogenase (SdhCDAB) catalyzes the oxidation of succinate to fumarate in the Krebs cycle, and during turnover, it produces superoxide radicals. SdhCDAB is a good model system for the succinate dehydrogenase (Sdh) found in the mitochondrial respiratory chain (complex II), as the subunits are structural homologues. Although mutations in sdh genes are reportedly associated with a variety of mitochondria-related diseases, the molecular mechanism of these diseases is poorly understood. We have investigated the effects of site-directed mutations around the heme (SdhD-H71L and SdhC-H91L), and at the ubiquinone-binding site (Q site; SdhC-I28E), on enzyme activity and production of superoxide radicals. The mutations SdhD-H71L and SdhC-I28E, but not SdhC-H91L, significantly reduce the succinate-ubiquinone reductase activity of the enzyme. All 3 mutant enzymes produce more superoxide than the wild-type enzyme, indicating that disturbance of the heme or the Q site can enhance superoxide production. The presence of a Q-site inhibitor reduces superoxide production significantly. Furthermore, the yield of superoxide is substrate dependent and increases with succinate concentration from 0.1 to 10 mmol/L. Our results indicate that, in SdhCDAB, the Q site with bound ubiquinone is an important source of superoxide radicals.

Binding Sites↗