Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 679-526-3
CAS number: 337906-36-2
distribution/ dose group: The
organs collected from number of rats/ dose group are as follows:
5 rats (vehicle control and test substance treatment group) and 6 rats
5 rats (from all treatment groups)
bladder epithelium: 6 rats (vehicle control), 5 rats (test substance
treated) and 7 rats (positive control)
All animals treated with 50 and 100 mg/kg bw test article did show
ruffled fur and pallor, as well as a red discolouration of the urine,
indicating a good bioavailability of the test material.
No mortality was observed in any of the treated animals.
Cells of vehicle controls used for assessment revealed good cell
viabilities fulfilling our cell quality criteria. No relevant cytotoxic
effects could be observed in liver, stomach and urinary bladder
epithelium cells of rats exposed to test substance. The same was true
for cells of all evaluated organs of the positive control animals.
OF POSITIVE CONTROL:
Roughened fur, pallor was observed in positive control animals. Clear
increases in tail length above the acceptance criteria for the positive
control (≥ 30% increase above the mean vehicle control value) were
observed in liver, stomach and urinary bladder epithelium of all
positive control treated rats used for assessment at a sacrifice time of
3 h after treatment. The increase in tail length after treatment is as
1. Mean Tail Length/ Dose Group of The Rat Comet Assay In Vivo after
treatment with Methoxymethyl PPD Sulfate (Study # T 4072906)
(mean tail length ± SD)
Urinary bladder epithelium
22.66 ± 1.8
23.4 ± 2.6
17.79 ± 1.8
25 mg/ kg bw of test substance
30.07 ± 5.2
22.15 ± 2.3
18.00 ± 2.3
50 mg/ kg bw of test substance
28.00 ± 4.8
24.11 ± 1.8
18.56 ± 1.9
100 mg/ kg bw of test substance
25.71 ± 5.0
23.03 ± 3.8
17.98 ± 2.5
*40.22 ± 4.5
38.88 ± 1.1
**26.52 ± 2.8
Mean of 6 animals
The aim of this study was to assess the
potential genotoxicity of 2-METHOXY-METHYL-PPHENYLENEDIAMINE SULFATE in
the Comet assay in liver, stomach and urinary bladder epithelial cells
after in vivo treatment of male rats. The test material was dissolved in
deionised water and was administered via gavage (dosing volume 20 mL/kg
bw) twice to 5 male Wistar rats at doses of 0, 25, 50 and 100 mg/kg
bw/day with a time difference of 20 hours between both administrations.
Animals were sacrificed 3 hours after the second administration. Cells
of the liver, stomach and urinary bladder epithelium were investigated
in this Comet assay.
The selection of the
2-METHOXY-METHYL-P-PHENYLENEDIAMINE SULFATE doses was based on two pilot
studies. In the first pilot study three male rats were orally
administered 2-METHOXY-METHYL-P-PHENYLENEDIAMINE SULFATE at a dose of
2000 mg/kg bw. All animals died shortly after application. In a second
pilot study, three male rats received 200 mg/kg bw. and four male rats
were treated with 100 mg/kg bw at the first application. The application
volume was 20 mL/kg. At 200 mg/kg bw. two animals died within 19 hours
after treatment. The surviving animal was sacrificed before the second
treatment due to the fact that the MTD was exceeded. At 100 mg/kg bw one
hour after this dose and before a second dose was administered the
following symptoms were recorded: reduced motility, roughened fur, discoloured
urine (reddish). A second dose of 100 mg/kg bw was administered 20 hrs
following the first dose. Directly after the second dose the following
symptoms were observed: roughened fur, pallor, hunched posture. Twenty
hours after the second dose discoloured urine (brownish) was observed.
Forty eight hours after the second dose all animals showed increased
intake of water and frequent micturition. None of the animals died.
The positive control group (4 male rats)
received 300 mg/kg bw ethyl methane sulfonate (EMS) in deionised water
once via gavage. Two animals were sacrificed 2 hours after treatment and
two animals were sacrificed 3 hours after treatment. Portions of the
liver, stomach, and urinary bladder were removed, processed, and
analyzed for DNA damage using the comet assay. For each comet sample
analyzed, 100 cells (50 cell per
slide, if possible) were scored for DNA
migration. In addition, 100 cells were assessed for cytotoxicity using
the trypan blue dye exclusion test.
All animals treated with 50 and 100 mg/kg bw
test material did show ruffled fur and pallor, as well as a red
discolouration of the urine, indicating a good bioavailability of the
Slight increases in the mean tail length
were detected in the livers of 2-3 out of 5 rats in each of the dose
groups after oral treatment with 2-METHOXY-METHYL-P-PHENYLENEDIAMINE SULFATE
(see table 1 below for group mean + SD values). Due to the lack of a
(an inverted dose-response was observed),
the relatively small increase in tail length, and the fact that there
was no consistent effect within the dose groups (a similar proportion of
responding animals in each dose group), the result for the liver was
considered to be of questionable biological relevance.
No biologically relevant increase of the
tail length value was observed in cells of the stomach and the urinary
bladder epithelium after oral treatment of rats with
The tail length of positive control rats was
markedly increased when compared to the negative control animals for
liver, stomach and urinary bladder epithelium cells, demonstrating the sensitivity
of the test system for the detection of genotoxic effects.
Based on these results and under the
conditions described, 2-METHOXY-METHYL-PPHENYLENEDIAMINE SULFATE was
considered to produce equivocal results in the comet assay in vivo in
rat liver cells. 2-METHOXY-METHYL-P-PHENYLENEDIAMINE SULFATE was considered
to be non-genotoxic in the comet assay in vivo in rat stomach and
urinary bladder epithelium cells.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again