1,3,3-trimethyl-N-(2-methylpropylidene)-5-[(2-methylpropylidene)amino]cyclohexanemethylamine

Endpoint summary

Description of key information

No studies with respect to these endpoints have been performed

Additional information

There were no studies available in which the toxicokinetic properties (distribution, metabolism, elimination) of 1,3,3 -trimethyl-N-(2 -methylpropylidene)-5 -[(2 -methylpropylidene)amino]cyclohexanemethylamine (Vestamin A139) were investigated. Therefore the following remarks on the toxicokinetics of Vestamin A139 are based on physico-chemical properties of the compound and on toxicological data.

Vestamin A139 is a substance having a molecular weight of 278,48 g/mol. It is a liquid, with a partition coefficient Kow at 25 °C: Kow = 158489  /  log Kow = 5.2 (at pH 7.5). However, due to the rapid hydrolysis of Vestamin A139 such partitioning is of low relevance for the distribution of the substance. The substance is hydrolytically unstable at pH 4,7 and 9 (half-life less than 12 hours; see IUCLID chapter 5.1.2) (Hüls AG 1996). It is likely that the substance Vestamin A139 will rapidly hydrolized to the reaction products isophoron diamine and isobutyraldehyde in the stomach of rats after oral application due to the low pH value. Vestamin A139 will most likely be hydrolyzed before it will be bioavailable after inhalation or oral uptake. For this reason a supporting assessment for the hydrolysis reaction products isophorone diamine and isobutyraldehyde has been chosen.

Vestamin A139 hydrolyses to approximately 60% isophoron diamine and approximately 40% isobutyraldhyde.

Isobutyraldehyde will rapidly be metabolized to isobutyric acid via the aldehyde dehydrogenase, and therefore exists only transiently systemically. The metabolic fate of isobutyric acid has been studied in rats (DiVincenzo G.D. and Hamilton M.L., 1979). After administration via gavage to male and female Charles River CD rats radioactive labelled isobutyric acid was eliminated rapidly in the breath as expired CO₂for the major part. A minor part was excreted via the urine and feces. Isobutyric acid rapidly disappeared from the plasma. These data demonstrate that isobutyric acid is rapidly metabolized to CO₂.

For the hydroysis product isophorone diamine, "No studies with respect to these endpoints have been performed." cited from SIAR for SIAM 18 (Paris, April 2004).

Human toxicokinetic inhalative in vivo data from the substance Isophorone diisocyanate (CAS: 4098-71-9) is available that can be used to describe some toxikokinetic properties of Isophorone diamine, because Isophorone diisocyanate hydrolyses rapidly and spontaneously to the corresponding amine (Isophorone diamine) after ingestion into the body. Partly cited from SIAR for SIAM 23 (Jeju, Korea, October 17-20, 2006): "Three healthy male volunteers were exposed in a 5.6 m³exposure chamber to 3-isocyanatomethyl-3,5,5-trimethyl- cyclohexyl isocyanate concentrations of 0.0121, 0.0177, and 0.0507 mg/m³for 2 hours at day 1, 3, and 5, respectively. All urine was collected for 16 days, and blood samples were taken before and half an hour after exposure, and daily on exposure-free days. After hydrolysis (…note: here hydrolysis with 3M NaOH during 4 hours…) 3-isocyanatomethyl-3,5,5-trimethyl- cyclohexyl isocyanate was determined as 3-aminomethyl-3,5,5-trimethylcyclo- hexylamine. When working up samples from exposed persons without hydrolysis, no 3-aminomethyl-3,5,5-trimethylcyclohexylamine was seen. This indicates that the test substance was available in the urine only as conjugates. Hydrolysis had to split the conjugates and convert any residual isocyanate functions that might have been stabilized by conjugation, to amine functions. The average urinary elimination half-time was 2.8 hours. The average urinary excretion of the corresponding amine was 27% (range 19 -46%). An association between the estimated inhaled dose and the total excreted amount was seen. No 3-aminomethyl-3,5,5-trimethylcyclo- hexylamine was found in hydrolyzed plasma (Tinnerberg et al., 1995)." The experimental study results derived from Isophorone diisocyanate indicate that Isophorone diamine may be predominantly eliminated via the urine with an average urinary elimination half-time of 2.8 hours. Furthermore the experimental findings indicate that Isophorone diamine is present only as conjugates in the urine.

Because of the low partition coefficient n-octanol/water (log Pow=0.99) and because of the low calculated bioaccumulation factor (BCF=3.16) a significant accumulation of Isophorone diamine in the organism is not expected.