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EC number: 204-137-9
CAS number: 116-37-0
Numeric (log mol/L)
Numeric (log Papp in 10-6 cm/s)
Intestinal absorption (human)
Numeric (% Absorbed)
Numeric (log Kp)
P-glycoprotein I inhibitor
P-glycoprotein II inhibitor
Numeric (log L/kg)
Fraction unbound (human)
Numeric (log BB)
Numeric (log PS)
Numeric (log ml/min/kg)
Renal OCT2 substrate
Max. tolerated dose (human)
Numeric (log mg/kg/day)
hERG I inhibitor
hERG II inhibitor
Oral Rat Acute Toxicity (LD50)
Oral Rat Chronic Toxicity (LOAEL)
Numeric (log mg/kg_bw/day)
Numeric (log ug/L)
Numeric (log mM)
pkCSM software (Pires et al, 2015) is a computational approach that usesgraph-based
signatures to develop predictive models of central ADMET properties for
to this model, the substance has a poor water solubility (-4.918).
A high oral absorption is expected as demonstrated by theCaco-2
permeability predicted >0.90 (1.493). In addition, the intestine
absorption is predicted around 93.7%. In contrary, the compound is
considered to have a relatively low skin permeability as a logKp > -2.5
is observed (-2.957).1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol
is susceptible to be a substrate of theP-glycoprotein
transporter and does not seem to be a P-glycoprotein I/II inhibitor.
distribution in tissue is expected to be moderate with a predicted
steady state volume of distribution of 0.257 and an unbound fraction to
plasma proteins of 0.134. The Blood Brain Barrier permeability is also
expected moderate as comprised between log -1 et 0.3 (0.179). With a
logPS comprised between > -2 and
< -3, a low penetration into the Central Nervous System (CNS) is
not likely to be metabolised by either 2D6 or 3A4 cytochrome P450
isoforms. However, the model predicts a possible inhibition of one or
several isoforms (CYP1A2/CYP2C19/CYP2C9/CYP2D6/CYP3A4).
Clearance of the compound, represented by the combination of hepatic
clearance (metabolism in the liver and biliary clearance) and renal
clearance (excretion via the kidneys) is expected to be high as >= 1
mL/min/kg (1.227). However, the substance does not seem to be a
substrate of the renal OCT2 protein transporter.
metabolism of 1,1'-isopropylidenebis(p-phenyleneoxy)dipropan-2-olb y
cytP450 was evaluated by the Xenosite P450 Metabolism 1.0 software.
XenoSite is able to predict the site of metabolism (SOM) of a molecule
for cytP4501A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 CYP isoforms.
Xenosite computes a probability score varying between 0 and 1 (a high
probability to be a SOM is characterized by a high score), which
reflects both the confidence of the model that a particular atom is
metabolised and the statistical likelihood that its prediction for that
atom is correct, but they do not explicit model selectivity (which
molecules are substrates of a given CYP enzyme). According to the cyt
P450 isoforms and the substance isomers, No prediction regarding a
preferential metabolism mechanism or site can be drawn.
dermal absorption of 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol
leads to the following results, obtained
using the SkinPerm v2.04 model according to
the input data:
Deposition over time
End time observation 8 hr
Total deposition (mg) or deposition rate (mg/cm²/hr)
Fraction absorbed (%)
Amount absorbed (mg)
Lag time stratum corneum (min)
Max. derm. abs. (mg/cm²/h)
No experimental toxicokinetic study is available on
However, as per REACH guidance document R7.C , information on
absorption, distribution, metabolism and excretion may be deduced from
the physical-chemical properties and QSAR predictions.
Based on the physical-chemical properties and QSAR predictions,
the absorption of 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol is
expected to be high by oral route and inhalation, but low by dermal
route. A moderate distribution in the body and an excretion in bile and
urines are expected.
The octanol/water partition
coefficient of 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol, being
3.3 to 3.6, and the molecular weight of 344.44 are favourable for
absorption. The water solubility of
1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol is moderate (109
In general, a compound needs to be
dissolved before it can be taken up from the gastro-intestinal tract
after oral administration. Potential for ionization may result in
impaired uptake since compounds need to pass the lipid membranes in the
gastrointestinal wall. The Danish QSAR database, a model for human
passive absorption, indicates an absorption between 50 and 100% for
respectively 1 mg and 1000 mg. In addition, the pkCSM models (Pires et
al, 2015) indicates an oral absorption of almost 100%. Thus, oral
absorption is considered 100% for risk assessment.
being a solid with a moderate water solubility (0.109 g/L) has the
potential for dermal absorption. Its molecular weight (344.44) and log
Pow (3.3 to 3.6) are indicative to be moderately favorable for dermal
uptake. While the criteria for 10% dermal absorption as given in the
Reach Guidance on information requirements and chemical safety
assessment (MW>500 and -1<log Pow >4) are not met, the IH skin perm
model calculates that the dermal absorption of
1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol is estimated to be
less than 1% (~0.5%) after 8 h for an instantaneous deposition of 1g or
a deposition over time of 2 mg/cm²/h. Thus, a dermal absorption of 10%
is considered as appropriate for risk assessment.
Based on the particle size of
1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol, particles < 100µm
which have the potential to be inhaled, are present in a small amount
(4.48%). Particles will predominantly settle in the nasopharyngeal
region (particles with aerodynamic diameter > 1-5 µm); the particles are
too large to reach the tracheobronchial or pulmonary region (no
particles < 5 µm). Part of the deposits in the nasopharyngeal region
will be coughed or sneezed out of the body, or swallowed, while the
moderate water solubility of
1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol (109 mg /L) indicates
that a part will dissolve into the mucus lining of the respiratory
tract. Next to the moderate water solubility, the log Pow > 0 (3.3 to
3.6) furthermore indicates a limited potential for absorption directly
across the respiratory tract epithelium. However for a risk assessment
purposes the inhalation absorption of
1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol is set at 100% as a
worst case assumption to be compliant to ECHA guidance.
No specific data is
available on the distribution of 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol.
In the repeated
toxicity studies, some effects were observed in different organs, that confirms
the distribution of the substance in the body.
According to the QSAR pkCSM, the substance
is moderately distributed into the body.
1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol does not seem undergo
biotransformation as demonstrated by the Xenosite model for CYT P450
Because of the moderate molecular
weight of 1,1-isopropylidenebis(p-phenyleneoxy)dipropan-2-ol, the
conjugates could either be excreted via the bile or the urine. According
to the pKcsm models (Pires et al, 2015), a high total clearance is
expected without the involvement of the renal OCT2 protein transporter.
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