1,5-naphthylene diisocyanate

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The following remarks on the toxicokinetics of 1,5-Naphthylene diisocyanate (NDI) are based on physico-chemical properties of the compound and on toxicological data (Jäger, 2010). Experimental toxicokinetic studies were not performed.

NDI is a white to yellowish organic solid with a very low vapour pressure under normal ambient conditions (8 x 10^-6hPa at 25°C), therefore inhalation exposure to the vapour is expected to be negligible. Currently available data on particle size during worst-case end-use of NDI indicate a thoracic percentage of 0.02 % (IGF, 2010), that can be inhaled by humans and may reach the thoracic region. Acute inhalation of a solid aerosol (dust) of NDI inhalable to rats did not reveal signs of systemic toxicity at the maximum attainable concentration of 541 mg/m3 (Pauluhn, 1995). Exposure to 96 mg/m3 and higher as aerosol were followed by concentration- dependent signs suggestive of irritation of the respiratory tract. At concentrations of 238 mg/m3 and above increased mortality was observed. Even subchronic (13-week) inhalation of NDI solid aerosol to rats revealed no signs of systemic toxicity (Pauluhn, 2010).

At ambient temperature NDI hydrolyses immediately (half-life < 1 hour) in demineralized water and in buffer solutions with pH 4, 7 and 9 (according to OECD TG 111). 1,5-diamino-naphthalene (NDA; molecular mass = 158) and carbon dioxide are found to be the main degradation products (Bayer Industry Services, 2006b). Due to hydrolytic instability of NDI in aqueous solutions neither water solubility nor log Pow value were determinable. Under physiological conditions it is expected that NDI decomposes in the GI tract mainly into NDA and carbon dioxide. Therefore intestinal absorption of NDI subsequent to oral ingestion may be limited. This assumption is confirmed by the data on acute oral toxicity in rats (LD50 cut-off ≥ 5000 mg/kg bw). In this study a dose of 2000 mg/kg bw was tolerated without mortalities, clinical signs, effects on weight gain or gross pathological findings (Schüngel, 2006).

 

An acute skin irritation study on rabbits revealed no systemic intolerance reactions after application of 0.5 g NDI formulated in corn oil/acetone (Schüngel, 2006). In this study a slight to moderate dermal irritation was seen. On the other hand, NDI proved as skin sensitizer in a local lymph node assay (LLNA) in mice (Vohr, 2006), therefore at least some dermal bioavailability after dermal contact is expected.

 

Based on the results of in vitro genotoxicity tests (negative with and without metabolic activation in two Ames tests; Herbold, 1989; JETOC, 1996) it is concluded that DNA-reactive metabolites of NDI will most probably not be generated in mammals in the course of hepatic biotransformation. This conclusion is confirmed by a negative result in a mouse micronucleus test in vivo with aerosol inhalation of NDI (Herbold, 2009).

 

In summary, systemic availability of NDI after oral, dermal or inhalation exposure is regarded to be low due to the high reactivity and hydrolysis in aqueous solutions.