Inhalation Toxicity of 1,6-Hexanediamine Dihydrochloride in F344/N Rats and B6C3F1 Mice

1,6-Hexanediamine (HDA) is a high production volume chemicalwhich is used as an intermediate in the synthesis of paints,resins, inks, and textiles and as a corrosion inhibitor in lubricants.Two- and 13-week studies of the toxicity of the dihydrochloridesalt of HDA (HDDC) were conducted in male and female Fischer344/N rats and B6C3F₁ mice using whole-body inhalation exposure.Both species were evaluated for histopatho-logic and reproductiveeffects, and rats were examined for clinical chemistry and hematologicchanges. In the 2-week inhalation studies, animals were exposedto 10–800 mg HDDC/m³, 6 hr per day. All rats, all femalemice, and two of five male mice in the high-exposure group diedbefore the end of the study. Surviving mice in this group hada dose-dependent depression in body weight gain. Clinical signswere primarily related to upper respiratory tract irritationand included dyspnea and nasal discharge in both species. Treatment-relatedhistopathologic lesions included inflammation and necrosis ofthe laryngeal epithelium of both species and the tracheal epitheliumof mice, as well as focal inflammation and ulceration of therespiratory and olfactory nasal mucosa. In the 13-week inhalationstudies, animals were exposed to HDDC at concentrations of 1.6–160mg/ m³ for 6 hr per day, 5 days per week. In addition to thebase study groups, a supplemental group of rats at each exposurelevel was included to assess the effect of HDDC on reproduction.No treatment-related changes in organ weights or organ-to-body-weightratios occurred in rats, and no treatment-related clinical signsor gross lesions were seen in either species. Chemical-relatedmicroscopic lesions were limited to the upper respiratory tract(larynx and nasal passages) in the two highest exposure groupsand were similar in both species. These lesions included minimalto mild focal erosion, ulceration, inflammation, and hyperplasiaof the laryngeal epithelium, in addition to degeneration ofthe olfactory and respiratory nasal epithelium. HDDC causedno significant changes in sperm morphology or vaginal cytologyand no significant adverse effects on reproduction in rats ormice. Hematologic and clinical chemistry changes in rats wereminor and sporadic and were not accompanied by related histologicfindings. HDDC did not increase the frequency of micronucleatederythrocytes in mice. In summary, the toxicity of HDDC to ratsand mice was a result of the irritant properties of the chemical,was limited primarily to the nasal passages and upper airways,and was consistent with the effects of other irritant chemicalsadministered by inhalation.