Development of a chronic inhalation reference value for hexamethylenediamine using an exposure model based on the dihydrochloride salt

Abstract

The Texas Commission on Environmental Quality has developed a chronic inhalation Reference Value (ReV) for hexamethylenediamine (HMDA, CAS 124-09-4) based on respiratory effects identified in an animal study. HMDA is used in the fiber and plastics industry as an intermediate in the production of nylon, high-strength resins and polyamide adhesives. As a toxicant, HMDA acts primarily as a respiratory irritant with effects occurring in the upper respiratory tract, although systemic effects have been noted at higher concentrations. ReVs are chemical-specific air concentrations derived to protect human health. Acute and chronic ReVs were developed for HDMA based on an inhalation study conducted by the National Toxicology Program (NTP), which used the salt of HMDA, hexamethylenediamine dihydrochloride (HDDC, CAS 6055-52-3). For the chronic evaluation, rats and mice were exposed to 0, 1.6, 5, 16, 50 and 160 mg HDDC/m³ for 13 weeks. The critical effect identified for the most sensitive species was hyaline degeneration in the olfactory epithelium in mice. The data provided in this study were suitable to benchmark concentration (BMC) modeling. Dosimetric adjustments using the rat and mouse Multiple-Path Particle Dosimetry Model (version 3.0) were made to the 95% lower limit of the BMC(10) to determine the human equivalent point of departure. Uncertainty factors were applied to account for variation in sensitivity within the human population, toxicodynamic differences between mice and humans, and use of a subchronic study. The ReV was initially calculated for HDDC and then adjusted for HMDA. The chronic ReV is 1.8 µg/m³ for respirable HMDA ≤ 10 µm in diameter.

• Amines
• diamines
• hexamethylenediamine
• inhalation

Acknowledgements

We would like to acknowledge the editorial review and useful comments from Dr Ross Jones.

Declaration of interest

The authors report no declarations of interest.