| TSCA Test Submissions | Diisopropylamine (CAS # 108-18-9) was evaluated for dermal sensitization in Harlet guinea pigs (5/sex) inducted with 0.3 ml occluded topical applications of 10% (v/v) test solution to shaved backs, 6 hours/day, 3 days/week for 3 weeks. Upon a third application, increasing dermal irritation required reduction of dosage to 0.3 ml of a 5% (v/v) solution, which continued to produce irritation ranging from moderate to severe. Two weeks later, the non-irritating dermal challenge upon virgin application sites produced no such signs of irritation, confirming cumulative irritation without dermal sensitization. Conversely, dermal irritation acquired during induction with DCNB (positive control) was identified as delayed hypersensitivity upon challenge 2 weeks later, which produced universal dermal irritation in response to an otherwise non-irritating dose.Acute inhalation toxicity was evaluated in groups of 10 Sprague-Dawley rats (5 male and 5 female) exposed to diisopropylamine at analytical concentrations of 0, 5.0 and 5.3 mg/l of air for four hours. Mortality was observed in one male rat in the 5.3 mg/l group and the LC50 for both sexes was considered to be greater than 5.3 mg/l. Clinical observations of animals at one or both exposure levels immediately following exposure and during the 14 day post-exposure period included labored breathing, tremors, high-pitched respiratory sounds, partially or completely closed eyes, nasal and ocular discharges and encrustation, ocular opacity, and pitted/raised corneal surface. After an initial body weight decrease in most exposed animals on post-exposure day 2, all animals gained weight and exceeded their pre-exposure weights by post-exposure day 14. Gross necropsy revealed corneal opacity.Diisopropylamine (CAS # 108-18-9) was evaluated in hepatocyte primary culture DNA repair assay. Isolated liver cells from Fischer-344 rats cultured in triplicate were exposed simultaneously to tritiated thymidine plus 10 concentrations of diisopropylamine ranging from 0.1 to 5000 ug/ml (cytotoxic concentration in preliminary assay), and 6 concentrations in the replicate assay from 10 to 2500 ug/ml for 18-21 hours at 37 degrees C. Each culture, washed and swelled in hypotonic solution, fixed and mounted on slides, was then dipped in autoradiographic emulsion and the cells exposed at -20 degrees C for 7 days, then developed and stained in methylgreen Pyronin Y. Thirty cells/culture, a total of 90 morphologically intact cells for each assay, were then subjected to quantitative autoradiographic grain counting to determine the net nuclear grain count (the nuclear count adjusted for background cytoplasmic uptake). Net grain counts were negative for all concentrations of test material and solvent control, reflecting a lack of diisopropylamine-induced DNA damage. Conversely, 2-AAF (the positive control) produced 39.9 and 51.2 net grain counts, respectively, in preliminary and replicate assays.Diisopropylamine (CAS # 108-18-9) was evaluated for subchronic dermal toxicity in groups of Charles River CD(SD)BR rats (3/sex/group) exposed 5 consecutive days/week for 1 month to 15, 50 or 150 mg/kg applications, undiluted doses at or below the established NOEL in range-finding study. A plastic collar hindered ingestion of test material during treatment. Volatility analysis of the undiluted test material under the conditions of study established that evaporation would results in diminished diisopropylamine availability at the sites of application (application site and manner of occlusion, if any, were unspecified). No overt effects of treatment were noted, other than mild dryness at the application sites and may have been attributable to repeated dosing and evaporation. Terminal necropsy revealed significantly decreased absolute (19%) and relative (12%) heart weights and increased absolute (4-5%) and relative (10-14%) testes weights in mid- and high-dose males. There was neither lost bodyweight nor any microscopic changes indicative of expressed toxicity in these organs. A dose-response relationship was not established for mild splenic congestion in females of all treatment groups and hematological and clinical chemistry findings were not clinically or biologically significant.Subchronic inhalation toxicity was evaluated in groups of 15 female and 15 male Charles River CD(SD)BR rats exposed to diisopropylamine vapor at mean concentrations (measured with an automatic infrared analyzer system) of 0, 0.1, 0.6 and 2.0 mg/l for 6 h/d, 5 d/week for about 4 weeks. The test atmosphere was generated by metering the test material through a nebulizer and introducing the resulting vapor along with air into the test chamber. There were 3 mortalities in the high-dose group. Clinical observations included eye and respiratory tract irritation and decreased body weights in mid- and high-dose rats and dose-related corneal keratopathy. Hematological studies revealed dose-dependent decreases in mean corpuscular volume, serum chloride, total protein, and albumin as well as dose-dependent increases in serum cholesterol in both sexesincreased red blood cell counts, hemoglobin, and hematocrit measurements in high-dose males and mid- and high-dose femalesand lowered white blood cell counts (reduced absolute number of lymphocytes) in treated males. Necropsy revealed inflammatory lesions in the nasal passages of males and females at all levels, thymic and seminal vesicle atrophy in high-dose males, and inflammatory lesions in the trachea, lung and corneas of high-dose males and females. |
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