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EC number: 222-852-4
CAS number: 3634-83-1
As XDI is a diisocyanate, it reacts with water. Isocyanates
hydrolyze readily in water to yield a carbamic acid, which
decarboxylates to produce CO2 and an amine; the latter can immediately
react with more isocyanate to yield a disubstituted urea. The hydrolysis
rate increases with electron-withdrawing substituents. Steric hindrance
also influences hydrolysis rate. Even at low pH, a hydrolysis Half-Life
< 10 minutes (25°C) has been found for isocyanates. Physicalchemical
characteristics of XDI requiring studies in aqueous surroundings (as
water solubility, octanol/water partition coefficient and surface
tension) can therefore not be determined on XDI
itself. The short hydrolysis half-life indicates that the parent
compound may only be present in the GI-tract for a limited period of
time. Hence, toxicokinetic predictions based on the characteristics of
the parent compound may be of limited relevance. As human absorption of
a substance always requires contact with aqueous solutions, it is
concluded that any uptake of XDI will be very limited (1, 3).
When considering the values for water solubility and partition
coefficient as determined for the CSA, it is anticipated that the
relative small molecular size (<200) and the moderate log Pow (between 0
and 4) of XDI are favourable for absorption, whereas the relatively low
water solubility (106.27 mg/L) is not favourable for absorption by the
GI-tract. Based on these physicochemical properties of XDI, a moderate
uptake by the GI-tract is anticipated, and for risk assessment purposes
the oral absorption of XDI is set at 50%. The results of the toxicity
studies do not provide reasons to deviate from this proposed oral
After absorption, XDI will react with water as stated above,
yielding carbamic acid, CO2, amine and disubstituted urea. Because of
the relative small molecular weight of XDI, the hydrolysis products
and/or metabolites will either be excreted via the bile or the urine.
Moderate log P values (between -1 and 4) are favourable for
absorption directly across the respiratory tract epithelium by passive
diffusion. The low vapour pressure of the substance (0.0206 Pa)
indicates that the substance will not be available for inhalation as
vapour. The relatively low water solubility is favourable for
penetration to the lower respiratory tract (2). Based on these
physico-chemical properties of XDI, for risk assessment purposes the
inhalation absorption is set at 100%. The results of the toxicity
studies do not provide reasons to deviate from this proposed inhalation
XDI, being a liquid, has the potential to be dermally absorbed.
The moderate log Pow of 3.07 is also indicative of dermal absorption.
The criteria for 10% dermal absorption as given in the Reach Guidance on
information requirements and chemical safety assessment (2) (MW>500 and
log Pow is outside of the range -1 to 4) is not met, and therefore 100%
dermal absorption of XDI should be considered for risk assessment
purposes. Although it is generally accepted that dermal absorption is
not higher compared to oral absorption, 100% dermal absorption should be
considered for risk assessment purposes as XDI has skin irritating
properties and damage to the skin surface may enhance penetration.
1. Martinez MN, Amidon GL. Mechanistic approach to understanding
the factors affecting drug absorption: a review of fundamentals. J Clin
Pharmacol 2002; 42: 620-43.
2. Guidance for the implementation of REACH. Guidance on
information requirements and chemical safety assessment. Chapter R.7c:
Endpoint specific guidance. European Chemical Agency, May 2008.
3. A. Parkinson. In: Casarett and Doull’s Toxicology, The basic
science of poisons. Sixth edition. Ed. C.D. Klaassen. Chapter 6:
Biotransformation of xenobiotics. McGraw-Hill, New York, 2001.
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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