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: 204-826-4
CAS number: 127-19-5
Plasma concentrations were determined following a
single 6-h exposure and following the last of a series of 10 exposures.
The test substance and NMAC plasma profiles for mice were not affected
by multiple test substance exposures, the plasma profiles of the test
substance and NMAC were similar to those from single exposure. Clearance
of the test substance and NMAC from plasma was rapid in mice following
300 and 500 ppm of test substance exposures. The test substance was not
detected beyond the 8-h time point (post-exposure) and NMAC was not
detected beyond the 12-h time point. Plasma profiles were not obtained
from mice receiving 50 or 150 ppm exposures. This was due to the time
required between termination of exposure and the first blood sample
(approximately 1 h). By the third time point (4 h post-exposure) the
test substance and NMAC were below the analytical detection limits (0.03 μg/mL).
AUC values of DMAC and NMAC
AUC comparisons for mice were difficult to
accurately assess due to the time required between exposure termination
and the dissipation of the test substance in room air to levels below 10
ppm following the opening of the exposure chambers (approximately 1 h).
With estimated test substance plasma half-lives of 0.3 to 0.5 h, the
post-exposure of the test substance AUC values were underestimated.
the increase in the test substance AUC values was 9-fold (single
exposure) and 4-fold (2-week exposure) between the 300 and 500 ppm
exposure levels. The AUC values of NMAC in mice increased in proportion
to the increase in the test substance exposure levels.
Plasma concentrations of DMAC and NMAC
The test substance and NMAC plasma concentrations
were determined at the termination of a 1-, 3-, or 6-h exposure to the
test substance. The test substance values for mice following all
exposures were lower for the 6-h compared to the 3-h exposure. This was
probably due to the time between exposure termination and the taking of
the post-exposure blood sample (30 min following termination of the 3-h
exposure vs. 1-h after the 6-h exposure). In mice, NMAC concentrations
were greater than companion test substance concentrations following 1-,
3-, and 6-h exposures to 50 or 150 ppm of the test substance and the 6-h
exposure to 300 ppm of the test substance.
Plasma half-lives of DMAC and NMAC
In mice, the approximate plasma half-lives ranged
from 0.3 to 0.5 h and 0.6 to 1.3 h for the test substance and NMAC,
respectively. Plasma half-lives were independent of exposure duration
(single vs. repeated exposures). All half-life estimations were based
upon plasma concentration data.
Urinary excretion of DMAC and NMAC
Urine samples from mice exposed to 50 and 150 ppm
of the test substance did not contain quantifiable amounts of the test
substance or NMAC. In mice the quantities of NMAC in urine typically
exceeded those of the test substance. The magnitude of this difference
decreased as exposure concentrations increased and quantities were equal
for rats receiving the single 500 ppm exposure.
exposures to the test substance were conducted with male mice
(Cr1:CD-I®(lCR)BR). Exposure concentrations were 50, 150, 300 and 500
ppm. The exposure routines consisted of single 1-, 3-, or 6-h exposures
and ten 6-h exposures (10 exposure days in 2 weeks). Area under the
plasma concentration curve (AUC) values were determined for the test
substance and its metabolite N-methylacetamide (NMAC), following 6-h
exposures (single exposure or last in a series of 10 exposures). The
range of exposures was chosen to assess the exposure-dependent nature of
the test substance pharmacokinetics in mice. Plasma profiles indicated
mice metabolized the test substance rapidly with plasma half-lives from
0.3 to 0.5 h for the test substance. The test substance AUC values from
mice were underestimated due to the required time (< 30 min) between
termination of exposure and the initial blood sample. NMAC was not
detected in plasma from mice beyond the 12-h post-exposure time point
for the 300 and 500 ppm exposures. Regardless of exposure level,
repeated test substance exposures to mice resulted in plasma profiles of
the test substance and NMAC similar to those from a single exposure. The
dose-dependent nature of the test substance AUC data and the absence of
effects of repeated 300 and 500 ppm of the test substance exposures
supported a toxicity-driven upper limit of 350 ppm for a chronic
inhalation study. The study and the conclusions which are drawn from it
fulfill the quality criteria (validity, reliability, repeatability).
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.
Damit Sie die Website optimal nutzen können, verwenden wir Cookies.
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