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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

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For an assessment of toxicokinetics read across is performed to HDI (CAS no. 822 -06 -0). For that purpose, the toxicokinetic assessment of HDI, which is based on experimental toxicokinetic studies in animals and volunteers, physico-chemical properties, and further toxicological data, is cited below. Given that the read across is justified, this is favourable to a toxicokinetic assessment solely based on PDI data, since the toxicokinetic database of HDI is much broader than that of PDI.

(For justification of read across see document attached to the endpoint summary.)

Read across to HDI (CAS no. 822 -06 -0):

HDI is a clear colourless liquid with a low vapour pressure under normal ambient conditions (0.007hPa at 20°C), therefore inhalation exposure to the vapour is expected to be low. After 1 hr exposure of guinea pigs to vapour concentrations ≥ 0.034 mg/m³ 14C-HDI the uptake of radiolabelled HDI into blood was immediate and increased linearly to a 2-4 hr postexposure peak (Kennedy et al., 1990). The14C-activity was cleared from the blood rapidly (no date) to a nanomolar level which persisted after 72 hr regardless of initial dose. Acute inhalation of HDI (vapour + condensation aerosol) to rats did not reveal signs of systemic toxicity at the maximum concentration of 151 mg/m³ (Pauluhn, report no. 25999, 1997). Exposure to 55 mg/m³ and higher were followed by concentration-dependent signs suggestive of irritation of the respiratory tract. At concentrations of 107 mg/m³ and above increased mortality was observed. Even life-time inhalation of HDI vapour to rats revealed no signs of systemic toxicity (Shiotsuka, report no. 1157, 1989).

In controlled studies in human volunteers 1,6-hexamethylene diamine (HDA) could be detected in the urine of HDI exposed persons (inhalation exposure) after acid hydrolysis as a biomarker for excretion of HDI or HDI-metabolites (Brorson et al., Int Arch Occup Environ Health 62, 385-389, 1990; Dalene et al., J Chromat 516, 405-413, 1990; Rosenberg and Savolainen, Analyst 111, 1069-1071, 1986). In a study with three volunteers each exposed to 0.012, 0.020 and 0.022 mg/m³ for 2 hours (2 days each between the exposures) the average urinary elimination half-time for HDA in hydrolysed urine was 2.5 hr (Tinnerberget al., Int Arch Occup Environ Health 67, 367-374, 1995). No HDA could be found in hydrolysed plasma during the exposure days (before and half an hour after exposure). Due to the analytical method using acid hydrolysis these studies give some insight in potential absorption and elimination, but not on metabolism.

At ambient temperature HDI is hydrolytically unstable (half-life in acetonitrile/water solution 0.23 hour; Bayer AG, 1999). HDA and carbon dioxide are found to be the main degradation products after contact with water (Sopac and Boltromejuk,Gig. Sanit. 7, 10 -13, 1974). Due to hydrolytic instability of HDI in aqueous solutions neither water solubility nor log Pow value were determinable. Under physiological conditions it is expected that HDI decomposes in the GI tract mainly into HDA and carbon dioxide. Therefore intestinal absorption of HDI subsequent to oral ingestion may be limited. Acute oral toxicity in rats revealed clinical symptoms at 263 mg/kg HDI as well as deaths at 788 mg/kg HDI within the first day of treatment (Kimmerleet al., Bayer AG, report no. 2146, 1970), possibly caused by the decomposition product HDA.

Due to a molecular weight of 168.2 g/mol and a calculated log Pow of 3.2 dermal absorption is conceivable. Furthermore, after contact of HDI with the surface moisture of the skin hydrolysis to HDA and carbon dioxide can be expected as well as reaction with nucleophiles like, NH- or SH-groups. HDI revealed corrosive properties to the skin (Schreiber, Bayer AG, 1981). Damage to the skin surface may enhance penetration of HDI and/or HDA. The assumption of a dermal absorption is confirmed by the data on acute dermal toxicity and skin sensitization. In the acute dermal toxicity study in rabbits hyperemia and swelling of the gastric mucosa as well as distinct hyperemia of the small intestine mucosa, peritineum, pleura, diaphragm and pancreas were seen macroscopically in all animals at 7000 mg/kg (Mürmann, Chemische Werke Hüls, report no. 372, 1985). In a guinea pig maximization test (GPMT) a strong skin sensitization potential could be detected for HDI (Schmidt and Bomhard, Bayer AG, report no. 11703, 1983).

Based on the results of two in vitro genotoxicity tests (negative with and without metabolic activation in an Ames test (Wagner and Klug, MA Bioservices Inc., 1998) and in a HGPRT test (San and Clarke, MA Bioservices Inc., 1998) it is concluded that DNA-reactive metabolites of HDI will most probably not begenerated in mammals in the course of hepatic biotransformation. This conclusion is confirmed by a negative result in a mouse micronucleus test in vivo with vapour inhalation of HDI (Gudi and Krsmanovic, MA Bioservices Inc., 1998).