| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Potential subchronic toxic effects of the test article, Diethylhydroxylamine (DEHA), were evaluated in a 28-day study in rats. The test article was administered via nose-only inhalation to three groups, each comprised of 15 male and 15 female Crl:CDBR rats, for a period of six hours per day, five days per week, for four consecutive weeks (minimum of 20 total exposures). The targeted exposure concentrations were 15, 150 and 1500 ppm. The test atmosphere concentrations were monitored by infrared absorbance and were found to be 15, 150 and 1506 ppm. ... 1-2 animals in the control, 15, 150 and 1500 ppm groups were found dead during the study. The deaths did not occur in an exposure-related manner and were not related to exposure to the test article. All other animals survived to the scheduled necropsies. The predominant treatment-related clinical signs were dried yellow dorsal posterior and urogenital matting, lack of grooming, eye closure and hypoactivity in males and females in the 1500 ppm group, and ataxia, paleness in color, walking on tiptoes and hunched posture in the females in this group. ... toxicity was exhibited in the 1500 ppm group by clinical signs, inhibition of body weight gain and food consumption, changes in white blood cell differential counts, various serum chemistry changes, reduced thymus gland weights-and increased liver weights. Medullary plasmacytosis was noted in the iliac and popliteal lymph nodes in males in the 1500 ppm group. Systemic effects in the 150 ppm group were limited to slight decreases in albumin and A/G ratio (females only). Based on data collected following a two-week nonexposure (recovery) period, all of these effects were considered to be reversible. Microscopic changes were noted in the nasal passages of male and female rats in the 150 and 1500 ppm groupsthese effects were considered to be due to local irritation, not systemic toxicity, and reversible. The hematological, serum chemistry and organ weight (thymus and liver) effects in the 1500 ppm group indicate that the liver and thymus were the target organs, however, no test article related histomorphological changes were seen in these tissues./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Not sensitizing in guinea pigs. After establishing the highest non-irritating dose concentration, a 3 week induction period was initiated during which 10 young adult, male, guinea pigs were treated with the test material applied as a 30% w/w solution in deionized water and 10 were treated with 0.08% Dinitrochlorobenzene (DNCB) in 95% ethyl alcohol (positive controls). During the induction period the animals were dosed on alternate days until a total of nine dose applications was achieved. Seventeen days after the ninth application a challenge dose (30%) was applied to a naive site on each guinea pig and approximately 24 and 48 hours later the animals were scored for a sensitization response (erythema and edema). INDUCTION PHASE: Test Animals: By the 4th induction many animals exhibited very mild erythema at both 24 and 48 hours post-dose. A slight increase in the severity of irritation was noted at several sites after inductions 8 and 9. . Positive Control Animals (0.08% DNCB): Varying degrees of erythema were observed throughout induction, increasing in severity toward the end of this period. CHALLENGE PHASE: Test Animals: No irritation was noted after challenge. . Naive Control Animals: No irritation was noted after challenge. Positive Control Animals (0.08% DNCB): Twenty-four and 48 hours after challenge all sites were erythemic, showing a faint to moderate response./LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of 20 male and 20 female CD-1(ICR)Br mice were treated either with 0, 3, 30, or 300 mg diethylhydroxylamine (DEHA)/kg-day (administered via the drinking water) from 57-112 days of age. For the four week period between 70 to 98 days of age, all animals received (via gavage) eight 1 mg doses of benzo(a)pyrene at 4 day intervals. One hundred thirty-seven animals survived the dosing period. Of these, 132 survived to 211 days of age at which time they were euthanized and necropsied. Gross lesions were observed only in the lungs and squamous portion of the stomach. Treatment with DEHA produced no significant effect on the lung tumor incidence of either sex. However, a significant increase in stomach tumors was observed in the females./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Female CD (SD) female rats were dosed once daily from GD6-GD15 with 87.4, 393 or 568 mg/kg diethylhydroxylamine by gavage. Animals were sacrificed on GD20. During gestation days 6 -9, a reduced mean body weight gain occurred in the 393 mg/kg/day group and a mean body weight loss occurred in the 568 mg/kg/day groupthe differences from the control group were statistically significant. Food consumption, evaluated as g/animal/day and g/kg/day, was reduced in the 393 and 568 mg/kg/day groups throughout the entire treatment period (gestation days 6-9, 9-12 and 12-16)the differences from the control group were statistically significant. All maternal animals survived to the scheduled necropsy on gestation day 20. Intrauterine growth and survival were unaffected by test article administration at any dose level. Parameters evaluated included postimplantation loss, live litter size, mean fetal body weights, fetal sex ratios and the mean numbers of corpora lutea and implantation sites. Fetuses (litters) available for morphological evaluation numbered 354(24), 326(22), 353(23) and 356(24) in the control, 87.4, 393 and 568 mg/kg/day groups, respectively. In conclusion, maternal toxicity was expressed by inhibition of body weight gain and food consumption at dose levels of 393 and 568 mg/kg/day. No maternal toxicity was evident at a dose level of 87.4 mg/kg/day. No developmental toxicity was apparent at any dose level. Based on the results of this study, the NOAEL (no observable adverse effect level) for maternal toxicity was considered to be 87.4 mg/kg/day, and the NOAEL for developmental toxicity was considered to be 568 mg/kg/day.For more Non-Human Toxicity Excerpts (Complete) data for DIETHYLHYDROXYLAMINE (11 total), please visit the HSDB record page. |
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