Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked

Endpoint summary

Description of key information

There were no studies available in which the toxicokinetic properties (absorption, distribution, metabolism, elimination) of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked were investigated. Based on the molecular structure, molecular weight, water solubility, and octanol-water partition coefficient significant oral, inhalative and dermal absorption is not expected. In fact, the available data give no indications for systemic availability, since no systemic toxicity could be concluded from the animal studies at all.

Additional information

Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked

(CAS No. 1001254 -87 -0); Information/Assumptions regarding toxicokinetics

The following remarks on the toxicokinetics of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked are based on physiochemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked is a white resinous solid (powder) having a molecular weight of >= 886.2 g/mol (The molecular weight is determined by the molecular weight of the main component (isophorone diisocyanate, oligomerization product (n = 3), blocked with acetone oxim) in the test substance.

It has a extremely low vapour pressure (7.6 * 10^-13Pa at 20°C; Smeykal, 2011) and is practically insoluble in water (393 µg/l at 20 °C; Lange, 2012) under normal ambient conditions. The partition coefficient octanol/water was determined as log Kow = 5.3 (range of values from log Kow = 5.0 to 5.6) at 24 °C (Hüls Infracor, 1998) indicating a highly lipophilic character of the substance. In the main hydrolysis test low rates of hydrolysis were determined for all pH values (pH 4, 7 and 9) at temperatures of 20 and 30 °C and moderate rates at 50 °C. The half-lives derived for 20 °C are 187 h (pH 4), 666 h (pH 7) and 1385 h (pH 9) (Lange, 2013). In the molecular structure of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked no functional groups with relevant acidic or basic character can be found. Therefore, no significant dissociation is expected at physiological pH values and beyond. The site of blocking is known to be physically stable. Only at elevated temperatures of > 90°C de-blocking occurs and reactive groups are released.

Oral and GI absorption: Due to a very high hydrolysis half-life of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked it is not expected that the substance is significantly hydrolysed in the gastro-intestinal tract. Furthermore, due to the relatively high molecular weight and the very low water solubility of the substance oral absorption is not expected. In fact, the acute oral toxicity is low with a LD₅₀(rat) of > 2000 mg/kg bw (Hüls AG, 1998). No mortality occurred.

There were no signs of systemic reaction to treatment and macroscopical examination revealed no abnormalitiesat the end of the observation period.

Dermal absorption: Dermal penetration of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked could not be excluded based on a log Kow that shows a high lipophility. Otherwise, due to the high molecular weight a significant dermal absorption is not expected. In fact, the acute dermal toxicity is low with a LD₅₀(rat) of > 2000 mg/kg bw (LPT, 2012). The test did not reveal any clinical signs of toxicity. No influence on animal behaviour or premature death was noted. The body weight gain was not influenced by the test item administration. No skin reactions were observed at the application site. The macroscopic examination did not reveal any changes. Furthermore,dermal treatment with cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked for 14 days did not cause any signs of local or systemic intolerance in rats. None of the animals died prematurely. No test item-related influence was noted on the body weight, food and drinking water consumption .Macroscopic examination at necropsy revealed no test item-related changes at any of the tested groups (LPT, 2012). No indications for a dermal uptake could be concluded from the skin sensitization test (modified LLNA (LPT, 2012), since no skin sensitization potential was detected.

Respiratory absorption: Due to the very low vapour pressure of the substance significant respiratory absorption via vapour is not expected. Furthermore, highly lipophilic compounds (log Kow > 4), particular those that are poorly soluble in water (1 mg/l or less), are expected to be poorly absorbed.

Distribution: The physico-chemical information (high molecular weight, low vapour pressure, lipophilicity and low water solubility) indicates that cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked could be distributed only to a low amount.

Accumulative potential: Bioaccumulation potential could not be excluded based on the physico-chemical data (e.g. log Pow). However, no indications of systemic availability could be concluded from the available animal studies, and therefore an accumulation potential for the substance seems to be questionable.

Excretion: No data are available regarding the excretion of absorbed cyclohexane, 5 -isocyanato-1 -(isocyanatomethyl)-1,3,3- trimethyl-, homopolymer, acetone oxime-blocked.

Based on the results of several in vitro genotoxicity tests (LPT, 2012; all performed with and without metabolic activation) it is concluded that DNA-reactive metabolites of cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked will not be generated in mammals in the course of hepatic biotransformation.