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o-TOLUIDINE CAS N°: 95-53-4 - UNEP Chemicals

o-TOLUIDINE CAS N°: 95-53-4 - UNEP Chemicals

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OECD SIDS o-<strong>TOLUIDINE</strong><br />

5. TOXICITY ID: <strong>95</strong>-<strong>53</strong>-4<br />

DATE: 07.01.2005<br />

.......................percent of dose<br />

Liver...........0.13.... ..0.12.... ....0.34........0.31<br />

Kidney........0.015.....0.017.......0.06........0.05<br />

Lung...........0.004.....0.003.......0.02........0.01<br />

Spleen........0.002.....0.002.......0.04........0.04<br />

Colon...........-----.... -----....... 0.004......0.006<br />

Bladder.......0.0004....0.0003....0.01........0.02<br />

METABOLITES:<br />

The results shown that N-acetylation and hydroxylation at the 4 position of<br />

o-toluidine are major metabolic pathways in rats. Minor pathways include<br />

hydroxylation at the 6 position, oxidation of the methyl group and oxidation<br />

of the amino group. Sulphate conjugates predominate over glucuronides by<br />

a ratio of 6:1.<br />

--detected substances in the urine:<br />

o-toluidine, azoxytoluene, o-nitrosotoluene, N-acetyl-o-toluidine, N-acetylo-aminobenzyl<br />

alcohol, 4-amino-m-cresol, N-acety-4-amino-m-cresol,<br />

anthranilic acid, N-acetylanthranilic acid, 2-amino-m-cresol and unidentified<br />

substances.<br />

--substances which were excreted via feces or via exhailed air were not<br />

mentioned<br />

Test condition : TYP: Metabolism and Distribution<br />

TEST ORGANISMS:<br />

- Animals: male F344 rats<br />

- Weight at study initiation: 250-300g<br />

ADMINISTRATION and EXAMINATIONS:<br />

- animals were subcutan injected with a single dose of either 50 mg or 400<br />

mg/kg ortho-[methyl-14C]-toluidine hydrochloride/kg bw as a suspension in<br />

0.9% NaCl<br />

-Immediately after injection animals were placed in metabolism cages.<br />

--The expired air was pased through two gas washers in series.<br />

--Urine and feces samples were cooled collected for time periods of 24h<br />

and 48h.<br />

-Animals were killed 48 h after injection and selected organs were removed<br />

and homogenized.<br />

Metabolites were identified using paper electrophoresis colum<br />

cromatography, thin layer chromatography, high pressure liquid<br />

chromatography and gas chromatography-mass spectrometry.<br />

Test substance : ortho-[methyl-14C]-toluidine hydrochloride and<br />

non labelled ortho-toluidine hydrochloride<br />

Reliability : (1) valid without restriction<br />

Flag : Critical study for SIDS endpoint<br />

13.12.2004 (129) (130)<br />

In Vitro/in vivo : In vivo<br />

Type : Distribution<br />

Species<br />

Number of animals<br />

: rat<br />

Males : 4<br />

Females<br />

Doses<br />

:<br />

Males : 500 mg/kg bw in corn oil/methanol (8:2)<br />

Females :<br />

Vehicle : other: corn oil/methanol (8:2)<br />

Route of administration : other: single application by gavage<br />

Exposure time : 72 hour(s)<br />

Product type guidance :<br />

Decision on results on acute tox. tests :<br />

Adverse effects on prolonged exposure :<br />

130<br />

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