title: Subacute inhalation toxicity of 2-chloro-4-toluidine in rats.
abstract: This article addresses results from a 4-wk inhalation exposure study in Wistar rats with the vapor and/or aerosol atmospheres of 2-chloro-4-toluidine. Groups of 10 rats/sex were nose-only exposed to mean analytical concentrations of 19.1, 115.1, and 702.3 mg/m3 using an exposure regimen of 6 h/day and 20-22 exposures within a time period of 4 wk. These concentrations were selected based on results from a repeated 5 x 6 h/day pilot study using concentrations of 27.1, 104.8, 381.6, and 1283.7 mg/m3. In a single 4-h exposure study at the maximum tested concentration of 7620 mg/m3, 1 of 10 female rats succumbed (no mortality in males), while no mortality occurred at 3293 mg/m3. In the 1- and 4-wk studies mortality occurred at 1283.7 and 702.3 mg/m3, respectively. Rats exposed for 4 wk to 702.3 mg/m3 displayed characteristic signs of toxicity that included cyanosis, respiratory distress, and significantly decreased body weights. Rectal temperatures were significantly decreased at 115.1 mg/m3 and above. Dark and enlarged spleens occurred at 702.3 mg/m3. At this concentration, prominent treatment-related effects included methemoglobinemia, reticulocytosis, red blood cells with Heinz bodies, decreased hemoglobin, hematocrit, and red blood cell counts. Borderline evidence of erythrocytotoxicty was noticed at 115.1 mg/m3 (based on a minimal increase in Heinz bodies). Spleen and liver weights were significantly increased at 702.3 mg/m3, whereas the thymus weight was decreased at 115.1 mg/m3 and above. Microscopic changes were found in the spleen (hemosiderosis) at 702.3 mg/m3. An atrophy of the olfactory epithelium in the nasal cavities occurred at 115.1 mg/m3 and above. Clinical pathology revealed changes pathognostic of hepatic effects, although microscopic examinations did not reveal any specific changes. The no-observed-adverse-effect level (NOAEL) of the 4-wk study was 19.1 mg/m3 and is based on the predominant atrophic changes of the olfactory epithelium and the minimal to borderline erythrocytotoxic effects at 115.1 mg/m3.
authors.affiliation: Institute of Toxicology, BAYER HealthCare AG, Wuppertal, Germany. juergen.pauluhn@bayerhealthcare.com
authors.forename: Jürgen
authors.initials: J
authors.lastname: Pauluhn
mesh_terms: D000336:Aerosols; D000818:Animals; D005260:Female; D019570:Inhalation Exposure / Q000009:adverse effects*; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D015394:Molecular Structure; D009666:Nose / Q000187:drug effects / Q000473:pathology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D014052:Toluidines / Q000737:chemistry / Q000633:toxicity*; D014835:Volatilization
chemical_list: D000336:Aerosols; D014052:Toluidines; C518671:2-chloro-4-toluidine