Biomedical subjects

W R Notten

Publications and source records attributed to W R Notten.

11 recordsLinked to original sources

PubMed1991

Effects of hexachlorobenzene and its metabolites pentachlorophenol and tetrachlorohydroquinone on serum thyroid hormone levels in rats.

Effects of administration of equimolar doses of hexachlorobenzene (HCB) and its metabolites pentachlorophenol (PCP) and tetrachlorohydroquinone (TCHQ) on serum thyroxine (TT4) and triiodothyronine (TT3) levels in rats were studied. Furthermore, it was investigated whether the observed effects were related to the serum levels of HCB or PCP. Rats received either corn oil (controls) or HCB, PCP or TCHQ in a single equimolar intraperitoneal dose of 0.056 mmol/kg. Results indicated that HCB did not alter serum TT4 and TT3 levels for a period up to 96 h after dosing. In contrast, PCP and TCHQ were both capable of reducing serum TT4 levels with a maximum effect between 6 and 24 h after exposure. TCHQ was more effective in repressing TT3 than TT4 blood levels. Dose-response experiments were carried out in order to obtain insight into the sensitivity of the observed effects. Rats received different doses of PCP or TCHQ intraperitoneally. The reductions of TT4 levels by PCP were inversely related to serum PCP levels in exposed animals, based on the toxicokinetics and dose-response profiles. Furthermore, PCP serum levels after HCB administration appeared too low to cause an effect. The results of this study indicate that not HCB itself, but rather its metabolites PCP and TCHQ may be involved in reduced serum thyroid hormone levels after HCB administration.

Animals↗

PubMed1991

Interactions of halogenated industrial chemicals with transthyretin and effects on thyroid hormone levels in vivo.

Previous results in experimental systems have suggested that hydroxylated PCBs may decrease thyroid hormone levels through associative interaction with transthyretin. In the present paper it was investigated whether this property was also shared by various industrial chemicals, mainly pesticides. In total, 65 compounds from 12 chemical groups were analyzed for direct interference with the T4 binding site of transthyretin using a competitive binding assay. Sixty per cent of the compounds were competitive at a concentration level of 100 microM. Relatively strong interactions were observed by several chlorophenols, chlorophenoxy acids and nitrophenols, as well as by individual compounds such as hexachlorobenzene, dicofol, bromoxynil and tetrachlorohydroquinone. Examples from these chemical groups, e.g. pentachlorophenol, 2,4-dichlorophenoxybutyric acid, dinoseb and bromoxynil, also reduced plasma TT4 levels in rats. In addition, bromoxynil decreased plasma TT3 levels. The results suggest the existence of a number of halogenated industrial chemicals with a potential for lowering plasma thyroid hormone levels through interference with hormone transport carriers.

Animals↗

PubMed1991

Hexachlorobenzene and its metabolites pentachlorophenol and tetrachlorohydroquinone: interaction with thyroxine binding sites of rat thyroid hormone carriers ex vivo and in vitro.

Previous results have indicated that hexachlorobenzene (HCB)-induced hypothyroidism may be caused by its main metabolite pentachlorophenol (PCP), and by tetrachlorohydroquinone (TCHQ), rather than by the parent compound. In the present experiments it was investigated whether hormone displacement from serum carriers could be a factor in the development of this hypothyroidism. In an in vitro competition assay PCP was an effective competitor for the thyroxine (T4)-binding sites of serum carriers, whereas HCB was ineffective. Ex vivo experimental results demonstrated occupation of T4-binding sites in sera from PCP-exposed animals but not in sera from HCB- or TCHQ-treated animals. Competing ability for T4-binding sites was still present in sera of PCP-exposed animals but was absent in HCB- or TCHQ-exposed animals. The results suggest that thyroid hormone displacement by the major metabolite PCP may play a role in HCB-induced hypothyroidism.

Animals↗

PubMed1987

Effects of the exposure profile on the inhalation toxicity of carbon tetrachloride in male rats.

To examine the effect of the exposure pattern on the inhalation toxicity of carbon tetrachloride (CCl4) two 4-week inhalation studies with this compound were carried out in male rats at basic exposure concentrations of 63 and 80 ppm and basic exposure periods of 6 hours per day, 5 days per week. The two main variables studied were interruption of the daily 6-hour exposures by 1.5 hours (2 X 3-hour exposures with a non-exposure interval of 1.5 hour), and peak loads of 5-7 times the basic concentration with or without 1.5-hour interruption of the daily 6-hour exposures. Adverse effects of CCl4 included abnormal activities of several enzymes in serum and liver, decreased quantity of microsomal proteins in the liver, increased relative liver weight, and hydropic and fatty degeneration of hepatocytes. As compared with uninterrupted, interrupted exposures increased more the activities of glutamic oxalacetic and glutamic pyruvic transaminase in serum; peak exposures only slightly affected these enzyme activities. Uninterrupted exposures caused less severe fat accumulation in and hydropic degeneration of liver cells than interrupted exposures with or without peak loads. In addition, uninterrupted exposure to 63 ppm CCl4 with peak loads resulted in more severe hydropic liver degeneration than uninterrupted exposure to the same concentration without peak loads. It was concluded that interruption of the daily 6-hour exposures by 1.5 hour did not result in less severe but rather in slightly more severe hepatotoxicity, and peak loads superimposed on a fixed concentration only slightly aggravated the toxic effects of CCl4 on the liver.

Alanine Transaminase↗

PubMed1986

Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats.

The effects of exposure pattern on the toxicity of acetaldehyde vapour were investigated in 4-week inhalation studies. Male rats were exposed to 500 or 150 and 110 ppm for 6 h per day/5 days per week. One group of animals was exposed without interruption, the exposure of a second group was interrupted for 1.5 h between the first and second 3-h periods, the exposure of a third group was similarly interrupted and for six 5 min periods exposure was increased sixfold. Peak exposures of up to 3000 ppm superimposed on 500 ppm acetaldehyde caused irritation and excitation, and reduced body weight gain. No such effects occurred after interrupted or uninterrupted exposure to 500 ppm acetaldehyde without peak loads. A reduced phagocytotic index of lung macrophages was found in each of the groups exposed to 500 ppm acetaldehyde, the effect being most marked in the group with superimposed peaks of 3000 ppm. Degeneration of the nasal olfactory epithelium was observed in rats uninterruptedly exposed to 500 ppm acetaldehyde. Interruption of the exposure or interruption combined with peak exposure did not visibly influence this adverse effect on the nose. No compound-related effects were seen in rats interruptedly or uninterruptedly exposed to 150 ppm acetaldehyde or interruptedly exposed to 110 ppm with peak loads of 660 ppm. As a consequence 150 ppm acetaldehyde can be considered a 'no-toxic-effect level' in male rats exposed for 6 h/day, 5 days/week, during a 4-week period.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

PubMed1979