Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on biogenic amines and their acidic metabolites in brain and cerebrospinal fluid of rats

Elo, Heikki A.; MacDonald, Ewen

doi:10.1007/bf00316434

Cited by 27 publications

(14 citation statements)

References 13 publications

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“…The homogenate was centrifuged at 10000g for 15 min at 4°C, then the supernatant was divided into two portions. The first aliquot was used for a high-performance liquid chromatographic analysis (HPLC) of indolamines by a method described by Mefford (21) and reviewed by Elo and MacDonald (22). The measured compounds consisted of tryptophan, dihydroxyphenylacetic acid (DOPAC), 5-hydroxytryptamine (serotonin, 5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA).…”

Section: Catecholamine Determinationmentioning

confidence: 99%

Alterations in central monoaminergic neurotrasmission induced by polycyclic aromatic hydrocarbons in rats

Stephanou

Konstandi

Pappas

et al. 1998

Eur. J. Drug Metab. Pharmacokinet.

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Benzo[alpha]pyrene (B[a]P) is a product derived from incomplete combustion of organic material and is considered responsible for chemically-induced cancer in humans. In the present study, the levels of noradrenaline (NA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the brains of female Wistar rats 6, 12, 24 and 96 h after a single dose of B[alpha]P (50 mg kg(-1) b.w., i.p.), and also after repeated administration of B[alpha]P (50 mg kg(-1) b.w., i.p., 2 x wk, 1 mo). The brain regions studied were the striatum, hypothalamus, midbrain and cortex. Catecholamines were measured using high performance liquid chromatography (HPLC) and electrochemical detection. Significant changes were observed in the striatum where NA, DA, DOPAC were decreased after 24 h and HVA was decreased after 6 h. In contrast, no major alterations occurred in 5-HT and 5- HIAA. In the hypothalamus, a significant decrease in NA was observed after 96 h. In the midbrain, the most important change observed was the decrease in NA after 24 h. A trend toward an increase in 5-HIAA was observed in the cortex after 6 h. The results demonstrate that B[alpha]P induces alterations in the dopaminergic and serotoninergic systems throughout the brain. These alterations may lead to behavioural and hormonal disturbances.

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Section: Catecholamine Determinationmentioning

confidence: 99%

Alterations in central monoaminergic neurotrasmission induced by polycyclic aromatic hydrocarbons in rats

Stephanou

Konstandi

Pappas

et al. 1998

Eur. J. Drug Metab. Pharmacokinet.

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“…Although the quantitative contribution of each of these saturation events to altered distribution of 2,4-D within the brain is unknown, such alterations to and within an endocrine-modulatory organ such as brain have the potential to initiate high-dose specific secondary modes of action. These include reduced clearance of potentially toxic neurotransmitter metabolites such as 5-hydroxy-3-indole acetic acid from brain by the choroid plexus OAT-1 transporter (5-HIAA; Kim et al 1988;Elo & MacDonald 1989) that ultimately have no quantitative relevance to adverse health outcome potential in humans exposed to far lower, non-saturating, environmental exposures.…”

Section: Differentiating Potential Endocrine Modes Of Action Based Onmentioning

confidence: 99%

Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis

Neal

Marty

Coady

et al. 2017

Critical Reviews in Toxicology

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A comprehensive weight-of-the-evidence evaluation of 2,4-dichlorophenoxyacetic acid (2,4-D) was conducted for potential interactions with the estrogen, androgen and thyroid pathways and with steroidogenesis. This assessment was based on an extensive database of high quality in vitro, in vivo ecotoxicological and in vivo mammalian toxicological studies. Epidemiological studies were also considered. Toxicokinetic data provided the basis for determining rational cutoffs above which exposures were considered irrelevant to humans based on exceeding thresholds for saturation of renal clearance (TSRC); extensive human exposure and biomonitoring data support that these boundaries far exceed human exposures and provide ample margins of exposure. 2,4-D showed no evidence of interacting with the estrogen or androgen pathways. 2,4-D interacts with the thyroid axis in rats through displacement of thyroxine from plasma binding sites only at high doses exceeding the TSRC in mammals. 2,4-D effects on steroidogenesis parameters are likely related to high-dose specific systemic toxicity at doses exceeding the TSRC and are not likely to be endocrine mediated. No studies, including high quality studies in the published literature, predict significant endocrine-related toxicity or functional decrements in any species at environmentally relevant concentrations, or, in mammals, at doses below the TSRC that are relevant for human hazard and risk assessment. Overall, there is no basis for concern regarding potential interactions of 2,4-D with endocrine pathways or axes (estrogen, androgen, steroidogenesis or thyroid), and thus 2,4-D is unlikely to pose a threat from endocrine disruption to wildlife or humans under conditions of real-world exposures.ARTICLE HISTORY

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“…In the incubated rabbit choroid plexus, 10 and 1001.tM concentrations of 2,4-D and 2,4,5-T inhibited the accumulation of 1 IxM labelled 5-hydroxy-3-indoleacetic acid (5-HIAA) by 40-65% (Pritchard 1980;Kim et al 1987). 2,4-D (30-200 mg/kg) causes the dose-dependent accumulation of endogenous acidic metabolites of neurotransmitters such as 5-HIAA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the rat brain and CSF (Elo and MacDonald 1989):…”

Section: Discussionmentioning

confidence: 99%

Distribution of three common chlorophenoxyacetic acid herbicides into the rat brain

1990

Self Cite

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The distribution of three common 14C-labelled chlorophenoxyacetic acid herbicides (2,4-dichlorophenoxyacetic acid or 2,4-D, 2-methyl-4-chlorophenoxyacetic acid or MCPA, 2,4,5-trichlorophenoxyacetic acid or 2,4,5-T) into the different brain areas was studied in rats pretreated with toxic doses of the herbicides (238-475 mg/kg). Also, their binding to proteins in rat plasma was determined in vitro by increasing the concentrations of chlorophenoxyacetic acids in the incubate from 0 to 1 mg/ml. Both 2,4-D and MCPA pretreatments increased brain concentrations of 14C-labelled herbicides more markedly than 2,4,5-T pretreatments did. No essential differences were found in the distribution between the different brain areas. Protein-unbound fractions of 2,4-D and MCPA in the plasma were clearly higher than those of 2,4,5-T but the highest herbicide concentration increased the protein-unbound fraction of 2,4,5-T more (7-13-fold) than of 2,4-D and MCPA (5-fold). The results suggest that the greater increase in the penetration into the brain of 2,4-D and MCPA than of 2,4,5-T during their intoxication is due to some factors other than the changes in their binding to plasma proteins and mere enhanced diffusion through the blood-brain barrier.

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Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on biogenic amines and their acidic metabolites in brain and cerebrospinal fluid of rats

Cited by 27 publications

References 13 publications

Alterations in central monoaminergic neurotrasmission induced by polycyclic aromatic hydrocarbons in rats

Alterations in central monoaminergic neurotrasmission induced by polycyclic aromatic hydrocarbons in rats

Weight-of-the-evidence evaluation of 2,4-D potential for interactions with the estrogen, androgen and thyroid pathways and steroidogenesis

Distribution of three common chlorophenoxyacetic acid herbicides into the rat brain

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