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EC number: 201-304-8
CAS number: 80-73-9
The substance is readily absorbed by the dermal and oral routes. No
data are available to indicate that absorption occurs via the inhalation
No specific study was performed on the
absorption/distribution/metabolism/excretion (ADME) of this substance
(DMI). However, data are currently available from in vivo toxicology
studies performed with this substance and are considered here.
Due to the physicochemical properties of DMI, octanol/water partition
coefficient Log Kow between -1 and 4 and high water solubility, it is
expected to be well absorbed. The lack of ionisable groups and low
molecular weight also favour absorption.
In an acute oral toxicity study, female rats in the high dose group
showed general signs of toxicity and adverse effects on a wide variety
Repeated oral administration of DMI to rats at doses up to 150 mg/kg/day
for a period of 28 days resulted in significantly lower testes weights
in comparison to controls. Macroscopic and microscopic changes in the
testes, effects on the epididymides and decreased sperm production were
Following oral administration of DMI in a reprotoxicity screening study
at dose levels of 4, 20 or 100 mg/kg/day, provided evidence that that
treatment of the test substance could affect the lactating behaviour of
the dams, but this could not necessarily be attributed to any toxic
effects of the test substance. Histopathological changes include slight
to marked atrophy of the seminiferous tubule and vacuolation of
interstitial cell hyperplasia in the testes of all males. The test
substance was shown to have a growth inhibition effect on offspring
These findings suggest that DMI causes systemic toxicity and is
well-absorbed by the gastrointestinal tract of rats.
Studies available via the dermal route include acute toxicity, skin
irritation, skin sensitisation and teratogenicity.
In the acute toxicity test, the test substance, dosed in a single
application at 1000 and 2000 mg/kg, caused an initial decline in
appetite with corresponding fall in bodyweight and amount of feces with
a return to normal values after 3 days or 5 days (low dose and high dose
respectively).In autopsy, no abnormality was observed in any of the
animals of any group.
In the skin irritation test, 0.5 ml of the test substance was applied to
intact and abraded skin on each of three New Zealand White rabbits. Each
treatment site was occluded with a cotton gauze patch secured with a
strip of surgical adhesive tape for the duration of the exposure period
(3 minutes, 1 hour and 4 hours). A single 4-hour, semi-occluded
application of the test material to the intact skin of three rabbits
produced very slight erythema. All treated skin sites appeared normal at
the 72-hour observation. No corrosive effects were noted. Three minute
and 1-hour semi-occluded applications of the test material to intact
skin of the rabbit produced no corrosive effects.
In skin sensitization study, conducted using the local lymph node assay
method, there were clear signs of general toxicity in the preliminary
test when mice were exposed to repeated doses of DMI.
In a teratogenicity main study, the test substance was applied dermally
for 6 hours/day on days 6-15 gestation at a dose of 0, 10, 100 and 400
mg/kg/day. All rats survived the test period and no changes in
behaviour or demeanour were observed at any dose level. There was no
treatment related effect at the dermal application site. A dose related
decrease in feed consumption was observed during days 6 through 21 of
gestation in the dams exposed to 100 and 400 mg/kg/day of test
substance, resulting in statistically significant decreases in body
weight and body weight gain during the dosing period.
Based on these results DMI is considered to be systemically toxic and
therefore readily absorbed by the dermal route.
Such a conclusion is supported by the United States Environmental
Protection Agency, Risk Assessment Guidance, 2004, which states that
chemicals such as the test substance that possess a low Kow will have
limited permeability through the lipid material of the stratum corneum,
but penetration by other routes (e.g., appendages such as sweat glands
or hair follicles or through regions of the stratum corneum with even
minor damage) may contribute significantly.
No data is available on absorption after inhalation. Due to high boiling
point, DMI is unlikely to be available in a vapour state.
Distribution, Metabolism, Excretion
The findings from oral administration in repeated dose/reprotoxicity
studies and from dermal application in developmental studies provide
evidence that the substance is absorbed via both oral and dermal routes.
Symptoms of general systemic toxicity in the repeat dose and
teratogenicity studies indicate distribution via oral and dermal routes,
although the only organ for which there is evidence of accumulation is
the testes in male rats.
No data are available for metabolism. Stability in water at pH 4, 7 and
9 suggests that the substance is unlikely to undergo abiotic degradation
during, or following, absorption.
The potential for absorption and distribution of the test substance,
combined with its high water solubility and low molecular weight
suggests that it will be readily excreted. The fact that appetite loss
and low body weight gains return to normal values a few days after
dosing suggest that the substance is being excreted (or possible
metabolised). In the 28-day repeat dose study carried out in conjunction
with the reproductive toxicity screening test, a similar improvement in
body weight gain was seen in the recovery group following substance
Results from in vivo toxicology studies performed with the test
substance reveal that it is readily absorbed via the gastrointestinal
tract and the skin. There is evidence of systemic distribution including
to the testes when the substance is administered via the oral route.
Dermal administration shows systemic distribution through general
systemic toxicity and low body weight gain. Nothing was observed in the
macroscopic or microscopic investigations to suggest bioaccumulation,
probably due to ready absorption and distribution across biological
membranes followed by excretion (and/or metabolism).
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.
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