Methylidynetri-p-phenylene triisocyanate

Endpoint summary

Additional information

The following remarks on the toxicokinetics of Triphenylmethane-4,4',4''-triisocyanate are based on toxicological data collected from studies conducted with the trade product (27% Triphenylmethane-4,4',4''-triisocyanate in ethyl acetate) (Oeben-Negele, 2012). Experimental toxicokinetic studies were not performed.

Triphenylmethane-4,4',4''-triisocyanate in ethyl acetate represents the pristine composition of the substance and is representative for its marketed form (27% Triphenylmethane-4,4',4''-triisocyanate in ethyl acetate (w/w)). During manufacturing of the trade product alreadysignificant amounts of oligomeric compounds are formed besides the certain isomerTriphenylmethane-4,4',4''-triisocyanate. Solvent removal from the trade product by distillation would increase the proportions of higher molecular weight constituents. According to this the physical chemical data of the solvent free trade product are not used for the toxicokinetic assessment of theTriphenylmethane-4,4',4''-triisocyanateexamined in the toxicological studies .Triphenylmethane-4,4',4''-triisocyanate is a solid, as demonstrated in the inhalation studies. While generating a liquid aerosol of the trade product, the actual exposure was to the solvent-free solid, due to evaporation of the solvent. Thus, in the inhalation studies the exposure can be considered as exposure to the rearly unchanged active ingredient Triphenylmethane-4,4',4''-triisocyanate. The toxicological effects resulting from inhalation exposure of aerosolized Triphenylmethane-4,4',4''-triisocyanate reveal a pattern characteristic for local irritation at the portal of entry (= the respiratory tract) and its sequelae with lack of systemic toxicity (Pauluhn, 2012). This mode of action is in line with other diisocyanates and wholly consistent with the chemical reactivity of the isocyanate functional group. Intestinal absorption of Triphenylmethane-4,4',4''-triisocyanate subsequent to oral ingestion is supposed to be low because the quite high molecular weight (ca. 367 g/mole corresponding to the idealized monomeric structure) and the bulky molecule do not favour absorption. This assumption is confirmed by the data on acute oral toxicity in rats (Krötlinger, 2002). In this study a dose of ca. 540 mg Triphenylmethane-4,4',4''-triisocyanate /kg bw (= 2000 mg/kg bw of 27% Triphenylmethane-4,4',4''-triisocyanate in ethyl acetate ) was tolerated without mortalities, clinical signs, effects on weight gain or gross pathological findings .  

An acute skin irritation study on rabbits revealed no systemic intolerance reactions after application of 27% Triphenylmethane-4,4',4''-triisocyanate in ethyl acetate (Leuschner, 2002). On the other hand , 27% Triphenylmethane-4,4',4''-triisocyanate in ethyl acetate proved as skin sensitizer in a Buehler test in guinea pigs (Vohr, 2003), therefore at least some dermal bioavailability after skin contact is expected.

Based on the results of in vitro genotoxicity tests (negative with and without metabolic activation in Ames test, Herbold, 2002; HPRT test, Wollny, 2012; Micronucleus test, Sutter, 2011 it is concluded that DNA-reactive metabolites of Triphenylmethane-4,4',4''-triisocyanate will most probably not be generated in mammals in the course of hepatic biotransformation. 

In summary, systemic availability of Triphenylmethane-4,4',4''-triisocyanate after oral, dermal or inhalation exposure is regarded to be low due to the high reactivity and increasing formation of oligomeric compounds under solvent free conditions.