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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 idicate that absorption occurs via the inhalation route.
No specific study was
performed on the absorption/distribution/metabolism/excretion (ADME) of
this substance (DMI). However, data are currently available fromin
vivotoxicology studies performed with this substance and are
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 of organs.
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 also observed.
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
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.
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
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
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 withdrawal.
Results fromin vivotoxicology
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).
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