Repeated Dose 28-day Toxicity Research Articles

In Vivo Evaluation of the Oral Toxicity of the Chlorobutanol.

Chlorobutanol (CB) is used as a preservative in cosmetics and has antibacterial activity. This study investigated the single- and repeated-dose 28-day oral toxicity of a CB solvent in Sprague Dawley (SD) rats. For the single-dose oral toxicity study, a dose of 62.5, 125, or 250 mg per kg of body weight (mg/kg b.w.) of CB was given once orally via gavage. For the repeated-dose 28-day toxicity study, the high dose was set as 100 mg/kg b.w./day, and the middle, middle-low, and low doses were set to 50, 25, and 12.5 mg/kg b.w./day, respectively. Body weight was not significantly changed in the repeated-dose toxicity study. Relative liver and kidney weights were significantly increased in both sexes of the 100 mg/kg b.w./day treatment group. However, there were histopathological changes in liver and kidney for females and males, respectively. These data suggested that the approximate lethal dose (ALD) of CB was over 250 mg/kg b.w./day in the single-dose study, and the no adverse effect level (NOAEL) for CB was over 50 and 12.5 mg/kg b.w./day for female and male rats in the repeated-dose toxicity study.

Toxicological Assessment of Bromochlorophene: Single and Repeated-Dose 28-Day Oral Toxicity, Genotoxicity, and Dermal Application in Sprague-Dawley Rats.

Bromochlorophene (BCP) has shown good properties in sterilization and antibacterial activity and is widely used as a household chemical. We evaluated the genotoxicity, single and repeated-dose 28-day oral toxicity, and dermal application of a BCP suspension in Sprague–Dawley (SD) rats. For the single-dose toxicity study, a dose of 25–1,000 mg per kg of bodyweight (mg/kg b.w.) of BCP was given once orally to SD rats. Mortality and clinical signs were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. For the repeated-dose 28-day toxicity study, the high dose was set at 1,000 mg/kg b.w. and the middle, middle-low, and low dose were set to 500, 250, and 125 mg/kg, respectively. Hematology and biochemistry parameters were examined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. A bacterial reverse mutation assay, in vitro chromosomal aberration assay, and in vivo micronucleus assay were performed to assess genotoxicity-dermal application exposure assessment of BCP in rats. A high oral approximate lethal dose (ALD) of 1,000 mg/kg was observed in the single-dose toxicity test. During the repeated-dose 28-day time period, most animal deaths after administration occurred during the first 3 weeks. The 1,000 mg/kg b.w. oral dose caused the death of six male rats (6/7) and four female rats (4/7). At 500 mg/kg b.w., the female rats showed mortality (1/7). For the biochemistry assays, cholesterol was increased significantly compared to vehicle in both sexes in the 250 and 500 mg/kg groups. Histopathological changes with treatment-related findings were observed in the pancreas in female rats treated with a high dose of BCP compared with the vehicle group. BCP showed no genotoxic effect. These data suggested that the ALD of BCP, estimated as a non-genotoxic substance, was over 1,000 mg/kg b.w. in the single-dose toxicity study, and the NOAEL of BCP was considered to be 250 mg/kg b.w. for male and female rats after repeated oral administration for 28 days under the present study conditions.

Toxicological evaluation of Lafoensia pacari A. St.-Hil. (Lythraceae) stem bark extract: Acute and subchronic studies in mice

This study evaluated the safety of Lafoensia pacari A. St.-Hil. (Lythraceae) stem bark hydroalcoholic extract (LPE) through acute and subchronic toxicological assessments in mice. In the acute toxicity evaluation, a single 2000 mg/kg oral dose of LPE was administered to mice and clinical observations were conducted for 14 days. For subchronic toxicity, LPE doses (6.25-1000 mg/kg) were administered orally for 28 days and biochemical, hematological, histopathological analyses and renal and liver expression of Ki-67 were carried out. The acute oral toxicity evaluation of LPE showed no toxicity in mice and it was was classified as category 5 (LD50>2000-5000 mg/kg). In a repeated dose 28-day toxicity study, LPE (100-1000 mg/kg) led to an increase in reticulocytes, which suggests a possible proliferative effect on blood cells. In addition, LPE (400-1000 mg/kg) of produced alterations in biochemical parameters, although no microscopic changes were found in the organs analyzed. A normal expression of the Ki-67 cell proliferation indicator was observed in the kidney and liver tissues, which suggests that LPE does not bring about changes in the proliferative activity of these organs. In conclusion, LPE should be used with caution, particularly in larger doses over longer periods and also in combination with other medication.