Toxicity of the styrene metabolite, phenylglyoxylic acid, in rats after three months' oral dosing

Publication: Research - peer-reviewConference article – Annual report year: 1998

Standard

Toxicity of the styrene metabolite, phenylglyoxylic acid, in rats after three months' oral dosing. / Ladefoged, Ole; Lam, Henrik Rye; Ostergaard, G.; Hansen, E. V.; Hass, Ulla; Lund, S. P.; Simonsen, L.

In: NeuroToxicology, Vol. 19, No. 4-5, 1998, p. 721-737.

Publication: Research - peer-reviewConference article – Annual report year: 1998

Harvard

APA

CBE

MLA

Vancouver

Author

Ladefoged, Ole; Lam, Henrik Rye; Ostergaard, G.; Hansen, E. V.; Hass, Ulla; Lund, S. P.; Simonsen, L. / Toxicity of the styrene metabolite, phenylglyoxylic acid, in rats after three months' oral dosing.

In: NeuroToxicology, Vol. 19, No. 4-5, 1998, p. 721-737.

Publication: Research - peer-reviewConference article – Annual report year: 1998

Bibtex

@article{cc86586567cd4706928aa979a2a6756b,
title = "Toxicity of the styrene metabolite, phenylglyoxylic acid, in rats after three months' oral dosing",
publisher = "Elsevier BV",
author = "Ole Ladefoged and Lam, {Henrik Rye} and G. Ostergaard and Hansen, {E. V.} and Ulla Hass and Lund, {S. P.} and L. Simonsen",
year = "1998",
volume = "19",
number = "4-5",
pages = "721--737",
journal = "NeuroToxicology",
issn = "0161-813X",

}

RIS

TY - CONF

T1 - Toxicity of the styrene metabolite, phenylglyoxylic acid, in rats after three months' oral dosing

A1 - Ladefoged,Ole

A1 - Lam,Henrik Rye

A1 - Ostergaard,G.

A1 - Hansen,E. V.

A1 - Hass,Ulla

A1 - Lund,S. P.

A1 - Simonsen,L.

AU - Ladefoged,Ole

AU - Lam,Henrik Rye

AU - Ostergaard,G.

AU - Hansen,E. V.

AU - Hass,Ulla

AU - Lund,S. P.

AU - Simonsen,L.

PB - Elsevier BV

PY - 1998

Y1 - 1998

N2 - Male Wistar rats were dosed with 0, 1250, 3750 or 5000 mg/l of phenylglyoxylic acid (PGA) (CAS no. 611-73-4) in the drinking water ad libitum for 3 months. During the entire treatment period, there were no gross signs of toxicity related to PGA. No changes in neurobehavior were found after using a functional observational battery or radial arm maze. An increased relative kidney weight was seen in the highest dose-group (Controls: 0.504 +/- 0.031 g/100 g b. wt.; 5000 mg PGA/I: 0.579 +/- 0.033 g/100 g b.wt.; p<0.01). No other organ weights were affected. Histopathology revealed no change in kidney structure. No changes in clinical biochemistry. in the highest dose-group three animals out of ten showed reduction in peripheral nerve myelin sheath thickness. No such changes were seen in the control group. The study revealed no changes in auditory brain stem response but minor changes in electroretinography. The noradrenaline (NA) concentration decreased in pens and thalamus whereas it increased in medulla oblongata and whole brain. The dopamine (DA) concentration increased in cerebellum, hippocampus, pens, and whole brain. The most marked DA increase was seen in hippocampus (Controls: 0.56 +/-0.10 nmol/g tissue; 5000 mg/l: 1.04 +/- 0.11 nmol/g tissue; p<0.001). The 5-hydroxytryptamine (5-HT) concentration decreased in cerebellum, cerebral cortex, hippocampus, and medulla oblongata, whereas it increased in thalamus. The yield of synaptosomal protein, synaptosomal NA, DA, and 5-HT concentrations, and DA uptake rate were not affected. When dosed males were mated with naive females, there were no differences between groups in the pregnancy rate, number of corpora luteae, implantations, live or dead fetuses, resorptions, preimplantation loss, or postimplantation loss. It is concluded that a part of the effects on kidney, peripheral nerves, and vision, which have previously been reported after exposure to styrene, might be induced by the styrene metabolite, PGA. If PGA has ototoxic effects in rats, the dosing in the present study is not sufficient to induce the necessary ototoxic concentration in blood. Alternatively, the ototoxicity of styrene, like toluene, may be caused the parent compound itself and not by a metabolite like PGA. (C) 1998 Inter Press, inc.

AB - Male Wistar rats were dosed with 0, 1250, 3750 or 5000 mg/l of phenylglyoxylic acid (PGA) (CAS no. 611-73-4) in the drinking water ad libitum for 3 months. During the entire treatment period, there were no gross signs of toxicity related to PGA. No changes in neurobehavior were found after using a functional observational battery or radial arm maze. An increased relative kidney weight was seen in the highest dose-group (Controls: 0.504 +/- 0.031 g/100 g b. wt.; 5000 mg PGA/I: 0.579 +/- 0.033 g/100 g b.wt.; p<0.01). No other organ weights were affected. Histopathology revealed no change in kidney structure. No changes in clinical biochemistry. in the highest dose-group three animals out of ten showed reduction in peripheral nerve myelin sheath thickness. No such changes were seen in the control group. The study revealed no changes in auditory brain stem response but minor changes in electroretinography. The noradrenaline (NA) concentration decreased in pens and thalamus whereas it increased in medulla oblongata and whole brain. The dopamine (DA) concentration increased in cerebellum, hippocampus, pens, and whole brain. The most marked DA increase was seen in hippocampus (Controls: 0.56 +/-0.10 nmol/g tissue; 5000 mg/l: 1.04 +/- 0.11 nmol/g tissue; p<0.001). The 5-hydroxytryptamine (5-HT) concentration decreased in cerebellum, cerebral cortex, hippocampus, and medulla oblongata, whereas it increased in thalamus. The yield of synaptosomal protein, synaptosomal NA, DA, and 5-HT concentrations, and DA uptake rate were not affected. When dosed males were mated with naive females, there were no differences between groups in the pregnancy rate, number of corpora luteae, implantations, live or dead fetuses, resorptions, preimplantation loss, or postimplantation loss. It is concluded that a part of the effects on kidney, peripheral nerves, and vision, which have previously been reported after exposure to styrene, might be induced by the styrene metabolite, PGA. If PGA has ototoxic effects in rats, the dosing in the present study is not sufficient to induce the necessary ototoxic concentration in blood. Alternatively, the ototoxicity of styrene, like toluene, may be caused the parent compound itself and not by a metabolite like PGA. (C) 1998 Inter Press, inc.

KW - Dopamine

KW - Organic solvents

KW - Neurotoxicity

KW - Renal effects

KW - Styrene metabolism

KW - Synaptosomes

KW - CAS no. 611-73-4

JO - NeuroToxicology

JF - NeuroToxicology

SN - 0161-813X

IS - 4-5

VL - 19

SP - 721

EP - 737

ER -