1,3-bis(isocyanatomethyl)benzene

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
For risk assessment purposes the following absorption factors were derived: oral absorption factor: 50%; dermal absorption factor: 100%; inhalation absorption factor: 100%
Short description of key information on absorption rate: 
A dermal absorption factor of 100% should be considered for risk assessment purposes.

Key value for chemical safety assessment

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100

Additional information

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.

When considering the calculated 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 absorption percentage.

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. 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 absorption percentage.

Discussion on absorption rate:

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 (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.