Subchronic dermal toxicity studies of Alcide Allay gel and liquid in rabbits.

Alcide is a germicidal agent which is highly effective in killing a wide range of bacteria and fungi. 2.0 g kg-1 Allay gel or placebo were applied once per day while 3.0 g kg-1 Allay liquid or placebo were administered three times per day over a 30 day period to the skin of albino rabbits. Allay gel and liquid contained either of two concentrations of sodium chlorite and lactic acid as active ingredients. The concentration of active ingredients, sodium chlorite and lactic acid, in the low dose gel was 25% of high dose gel and low dose liquid was 60% of high dose liquid. Moderate to severe erythema was observed only in the high dose gel group after 7 days of treatment, but skin appeared visibly normal by day 18. Histologically fixed skin at day 30, however, showed inflammatory changes in the high and low dose gel groups and hyperkeratosis in all gel groups. At the termination of the study, mean corpuscular hemoglobin concentration decreased significantly in the Allay gel and liquid groups compared to an untreated control group. In all gel treatments, BUN/creatinine levels decreased significantly. Hematology and clinical chemistry parameters, however, were within the normal range of values for the gel and liquid groups, indicating no clinically significant changes due to Allay treatment. Pancreas/body weight ratios were significantly reduced in all gel groups, while spleen, pancreas and ovary/body weight ratios were significantly higher in both liquid dosage groups. No histological changes were observed in any of these organs.

Teratologic studies on Alcide Allay gel in rabbits.

Alcide Allay gel, a highly effective germicidal compound, was evaluated for teratogenic potential in rabbits. Pregnant rabbits were administered 2 g/kg Allay gel (containing either of two concentrations of sodium chlorite as active ingredient) or placebo topically on days 6-18 of gestation. Moderate to severe erythema was recorded in the high-dose gel group on day 11 (Draize score = 3.5). By day 18, the skin of all rabbits in the high dose treatment group appeared normal. Decreased maternal body weight gain was observed in the low dose and placebo gel groups. Fetal weights and lengths were significantly reduced in all gel groups. There was some incidence of skeletal anomalies in all gel treated groups, however, these incidences were not statistically different from the control group. The commonly occurring skeletal defects were incomplete ossification of skull bones, small or missing sternebrae, and extra ribs. The incidence of visceral abnormalities in all gel groups was not statistically different from control animals. Visceral anomalies included heart displacement, fusion or serration of the liver, and kidney displacement. Alcide Allay gel at 2 g/kg was non-teratogenic to rabbit fetuses.

Subchronic vaginal toxicity studies of Alcide Allay gel and liquid in guinea pigs.

Alcide Allay, an antimicrobial preparation produced in gel and liquid forms, was evaluated for vaginal toxicity in guinea pigs. 1.0 g/kg Allay gel or placebo was administered intravaginally once per day over a 30 day period while 2.5 g/kg Allay liquid (containing either of two concentrations of sodium chlorite and lactic acid as active ingredients) or placebo was applied vaginally three times per day for 10 days. At the conclusion of the studies, hematology, blood and urine clinical chemistry tests and necropsies were performed. RBC, HGB, HCT, MCHC and direct bilirubin increased while CO2, SGPT and CPK decreased in blood after Allay liquid treatment. Creatinine, urea nitrogen and uric acid in urine were statistically reduced in the liquid groups. Hematology and clinical chemistry parameters were within the normal range of values reported in the literature for guinea pigs, indicating no clinical significance due to drug treatment. Significant differences in organ body/weight ratios were observed between controls and Allay gel and liquid groups. However, only the livers in the gel study and the vaginas in both studies were changed histologically.

Effect of benzyl chloride on rat liver functions.

Benzyl chloride (BCL) is extensively used in industry for the manufacture of dyes, perfumes, and pharmaceutical products. A previous study from this laboratory revealed the presence of liver steatosis of the microvesicular type and central focal inflammation in rats following the inhalation of BCL. This study was conducted to investigate the hepatotoxicity of intravenous (iv) BCL in rat. BCL (250, 25, and 0 micrograms/kg) was administered (iv) to rats, and serum enzyme tests were used to evaluate hepatic injury. After 10 min from BCL administration, serum glutamic-pyruvic transaminase and lactic dehydrogenase activities were significantly increased compared to the control group, while the values returned to normal within 1 h from the administration of BCL. Also, ornithine carbamyltransferase enzyme activity was significantly increased and reached a maximum as early as 0.5 h from the administration of BCL. Hepatic excretory function was investigated by the clearance of bromosulfophthalein (BSP) after 0.5 and 24 h from the administration of BCL. The clearance of BSP in both treatments was significantly slower compared to control group throughout the 24 h studied. Furthermore, BCL significantly decreased liver and blood glutathione values. This study revealed that BCL has the potential to cause hepatomalfunction.

Effects of Alcide gel on fetal development in rats and mice. II.

Alcide gel is a germicidal agent which is highly effective in killing a wide range of bacteria and fungi in vitro within 1 min. Alcide gel consists of sodium chlorite and lactic acid, parts A and B, respectively. Chlorine dioxide is formed when sodium chlorite and lactic acid, the active ingredients of Alcide, are mixed. The objective of this investigation was to study the teratogenic effects of Alcide gel both in rats and in mice. The gel was administered topically in doses of 1 and 2 g per kg body weight on days 6-15 of gestation. No toxic symptoms were observed following exposure of pregnant rats and mice to Alcide gel. Viability of the fetuses as well as weight, length and number of resorptions were quite similar compared with control groups. Fetuses were examined for external, visceral and skeletal anomalies. Some incidence of missing or incompletely ossified sternebrae, missing ribs and incomplete ossification of skull bones were observed from skeletal examination. Gastromegaly, kidney agenesis, heart displacement, interatrial septal defect, limb hyperflexion and club foot were observed from soft-tissue examination. These defects, however, were not significantly different compared with control animals. Alcide gel was not teratogenic at the doses tested.

Teratologic evaluation of Alcide liquid in rats and mice. I.

Alcide, a liquid sterilizer, was evaluated for teratogenic potential in rats and mice. Sodium chlorite and lactic acid, the active ingredients of this compound, form chlorine dioxide when mixed. Pregnant rats and mice were administered 1 ml and 0.1 ml, respectively, of Alcide liquid by gavage on days 6-15 of gestation. The general health of the dams was evaluated and the fetuses examined for external, visceral and skeletal malformations. There was no evidence of maternal toxicity among treated rats and mice. Fetal viability, weight, length and number of resorptions were comparable with control groups. Teratogenic toxicity was not detected in either species. There was some incidence of skeletal and visceral anomalies; however, these variances were not significantly different from control animals.

Pharmacodynamics of alcide, a new antimicrobial compound, in rat and rabbit.

Alcide is a germicidal preparation which has been shown to kill a wide range of common pathogenic bacteria as well as fungi, in vitro. This preparation is composed of Part A and Part B which contains sodium chlorite (NaClO2) and lactic acid as the active ingredients, respectively. The two parts are combined in equal volumes immediately prior to application resulting in the formation of chlorine dioxide (ClO2). Alcide gel was applied to the shaven backs of 18 female Sprague-Dawley rats in a 2.0-g/kg dose by combining 1 g of each part immediately prior to administration. This dose was applied for a period of 10 days to reach a steady state. On the 11th day, 36Cl-labeled Alcide gel, which contained Na36ClO2 in Part A, was administered to the animals in a 0.6-g dose (2.0 g/kg) containing 0.1 microCi. The half-life for 36Cl absorption was 22.1 hr while the elimination half-life was 64.0 hr. 36Cl was excreted by the kidneys with chloride (Cl-) and chlorite as the metabolites. Ninety-six hours after Alcide administration, radioactivity was highest in whole blood and lowest in fat. In a 90-day subchronic dermal toxicity study in rabbits, exposure to Alcide gel resulted in decreased glutathione concentrations in blood of the group receiving 2.0 g/kg Alcide as well as in the placebo gel group which received the same dose of gel.

Pharmacokinetics of Alcide, a germicidal compound in rat.

Alcide is a germicidal compound which is currently being used as a liquid sterilizer. This agent has the ability to kill a wide range of bacteria, viruses and fungi in vitro within 1 min. The active ingredients in this sterilizer are sodium chlorite and lactic acid. The kinetics of 36Cl-labelled liquid Alcide were studied in rats. After oral administration, the peak plasma level was obtained in 8 h. The half life for 36Cl absorption from plasma was 8.03 h, corresponding to a rate constant of 0.086 h-1, while the half life for 36Cl elimination from plasma was 48.02 h, corresponding to a rate constant of 0.014 h-1. At 144 h, radioactivity was highest in plasma followed by lung, kidney, skin, bone marrow, stomach, ovary, duodenum, ileum, spleen, fat, brain, liver and carcass. The greatest amount of activity in whole blood was present in plasma. Subcellular distribution revealed that 85% of the activity in the liver homogenate resided in the cytosol. Seventy per cent of total activity in plasma was located in the trichloroacetic acid (TCA) supernant, with 30% bound to the precipitated protein fraction. Urinary excretion accounted for most of the 36Cl eliminated. Radioactivity was excreted as chloride and chlorite in urine.