Thirteen-week subchronic rat inhalation toxicity study with a recovery phase of trivalent chromium compounds, chromic oxide, and basic chromium sulfate

The toxicity of trivalent chromium compounds, chromic oxide and basic chrom ium sulfate, was investigated in rats in a 13-week nose-only inhalation stu dy that included a 13-week recovery period. Nose-only exposures to insolubl e chromic oxide dust at 4.4, 15, or 44 mg/m(3) or soluble basic chromium su lfate dust at 17, 54, or 168 mg/m(3) (trivalent chromium equivalent concent rations of 3, 10, and 30 mg/m(3)) were carried out for 6 h/day, 5 days/week . No compound-related mortality occurred. General toxic effects, only obser ved with high-exposure levels of basic chromium sulfate, included sporadic signs of labored breathing and depressed body weights. No apparent compound -related effects were noted for sperm motility or morphology, for any conce ntration of either test material. Bronchoalveolar lavage fluid evaluations showed test material in mononuclear cells with chromic oxide and increased neutrophils, protein, lactic dehydrogenase and cellular debris with basic c hromium sulfate. The principle effects for both materials were primarily to the respiratory tract. Chromic oxide caused pathological changes in the br onchial and mediastinal lymphatic tissue and lungs, consisting of the prese nce of pigment-laden macrophages, lymphoid and septal hyperplasia, and inte rstitial inflammation similar to that observed with other inert dusts. Basi c chromium sulfate produced more severe and widespread effects in the nasal cavity, larynx, lungs, and mediastinal lymph node. Effects were characteri zed by accumulation of foreign material, infiltration of alveolar macrophag es, septal cell hyperplasia, and granulomatous and chronic inflammation. Pi gment was still present in chromic oxide and, to a lesser extent, in basic chromium sulfate-treated animals after the 13-week recovery period, with pa rtial recovery of the pathological lesions. A NOAEL was not established for either test material, but 4.4 mg/m(3) was thought to be near the NOAEL lev el for subchronic exposure to chromic oxide. The results of this study indi cate significant differences in toxicity to the respiratory tract between t rivalent chromium compounds chromic oxide and basic chromium sulfate. These are likely related to differences in acidity and water solubility, rather than chromium concentration per se. This conclusion is substantiated by the lack of effect on other internal organs.