Low Order Of Acute Toxicity Research Articles

Acute Oral Safety Study of Sodium Caseinate Glycosylated via Maillard Reaction with Galactose in Rats

In order to potentially use sodium caseinate (SC) glycated with galactose (Gal) in the food industry as a new functional ingredient with proved technological and biological properties, an evaluation of oral acute toxicity has been carried out. An acute safety study with SC-Gal glycoconjugates in the Wistar rat with a single oral gavage dose of 2,000 mg/kg of body weight was conducted. The SC-Gal glycoconjugates were well tolerated; no adverse effects or mortality was observed during the 2-week observation period. No abnormal signs, behavioral changes, body weight changes, or alterations in food and water consumption occurred. After this period, no changes in hematological and serum chemistry parameters, organ weights, or gross pathology or histopathology were detected. It was concluded that SC-Gal glycoconjugates obtained via the Maillard reaction were well tolerated in rats at an acute oral dose of 2,000 mg/kg of body weight. The SC-Gal glycoconjugates have a low order of acute toxicity, and the oral 50 % lethal dose for male and female rats is in excess of 2,000 mg/kg of body weight.

Acute oral safety study of dairy fat rich in trans-10 C18:1 versus vaccenic plus conjugated linoleic acid in rats

The acute oral toxicity of a trans-10 C18:1-rich milk fat (T10, 20% of total FA), and a trans-11 C18:1 + cis-9 trans-11 C18:2-rich milk fat (T11-CLA, 14% and 4.8% of total FA, respectively) was studied in rats receiving a single oral dose of 2000 mg/kg body weight (BW). T10 and T11-CLA milk fats were well tolerated; no adverse effects or mortality were observed during the 2-week observation period. Two weeks following a single oral dose of 2000 mg/kg BW of T10 and T11-CLA milk fats there were no changes in haematological and serum chemistry parameters (excepting plasma lipid) organ weights, gross pathology or histopathology. In rats treated with T10 milk fat a significant increase of triglycerides was observed. In contrast, in rats treated with T11-CLA milk fat significantly decreased triglycerides were detected. It was concluded that dairy fats rich in T10 and T11-CLA have a low order of acute toxicity, the oral lethal dose (DL 50) for male and female rats are in excess of 2000 mg/kg BW. Our results suggest that the T10 milk fat treatment tended to increase triglycerides concentrations, whereas the T11-CLA milk fat treatment tended to reduce it.

Review of the Toxicology of Mineral Spirits

This review of the toxicology of mineral spirits covers studies of the major classes of mineral spirits and several toxicologically important mineral spirit constituents. This review cites data from numerous previously unpublished animal toxicology studies conducted on mineral spirits during the past 30 years, expanding the existing database on the toxicology of this group of hydrocarbon solvents. The data can be used to better evaluate the potential effects associated with exposure to these materials, including health and environmental reviews such as the U.S. Environmental Protection Agency High Production Volume (HPV) chemical program and the Organization for Economic Cooperation and Development (OECD) HPV Screening Information Data Set (SIDS) program. The majority of animal toxicology studies in the available literature were conducted on mineral spirits categorized as ASTM D235 Type I Class A (149 degrees C to 213 degrees C boiling range; 8% to 22% aromatics) and demonstrate that Type I Class A mineral spirits have a low order of acute toxicity and do not produce significant systemic effects. Some additional studies conducted with ASTM D235 Type II Class C mineral spirits (177 degrees C to 213 degrees C boiling range; < 2% aromatics) suggest that Type II Class C mineral spirits have similar toxicity to Type I Class A mineral spirits, though there is some evidence that Type II, Class C mineral spirits have a lesser degree of central nervous system (CNS) effects than the higher aromatic containing Type I Class A materials. In addition, toxicity data on selected chemical constituents of mineral spirits (e.g., n-nonane, n-decane, n-undecane) indicate that these chemicals have similar toxicological properties to mineral spirits. Overall, the data showed that mineral spirits have a low order of acute toxicity and do not appear to produce toxicologically relevant systemic effects. Ongoing studies are evaluating the concerns associated with chronic low-level exposure and central nervous system effects.

Triethylene glycol HO(CH2CH2O)3H

TEG is a liquid higher glycol of very low vapor pressure with uses that are primarily industrial. It has a very low order of acute toxicity by i.v., i.p., peroral, percutaneous and inhalation (vapor and aerosol) routes of exposure. It does not produce primary skin irritation. Acute eye contact with the liquid causes mild local transient irritation (conjunctival hyperemia and slight chemosis) but does not induce corneal injury. Animal maximization and human volunteer repeated insult patch tests studies have shown that TEG does not cause skin sensitization. A study with Swiss-Webster mice demonstrated that TEG aerosol has properties of a peripheral chemosensory irritant material and caused a depression of breathing rate with an RD(50) of 5140 mg m(-3). Continuous subchronic peroral dosing of TEG in the diet of rats did not produce any systemic cumulative or long-term toxicity. The effects seen were dose-related increased relative kidney weight, increased urine volume and decreased urine pH, probably a result of the renal excretion of TEG and metabolites following the absorption of large doses of TEG. There was also decreased hemoglobin concentration, decreased hematocrit and increased mean corpuscular volume, probably due to hemodilution following absorption of TEG. The NOAEL was 20 000 ppm TEG in diet. Short-term repeated aerosol exposure studies in the rat demonstrated that, by nose-only exposure, the threshold for effects by respiratory tract exposure was 1036 mg m(-3). Neither high dosage acute nor repeated exposures to TEG produce hepatorenal injury characteristic of that caused by the lower glycol homologues. Elimination studies with acute peroral doses of TEG given to rats and rabbits showed high recoveries (91-98% over 5 days), with the major fraction appearing in urine (84-94%) and only 1% as CO(2). TEG in urine is present in unchanged and oxidized forms, but only negligible amounts as oxalic acid. Developmental toxicity studies with undiluted TEG given by gavage produced maternal toxicity in rats (body weight, food consumption, water consumption, and relative kidney weight) with a NOEL of 1126 mg kg(-1) day(-1), and mice (relative kidney weight) with a NOEL of 5630 mg kg(-1) day(-1). Developmental toxicity, expressed as fetotoxicity, had a NOEL of 5630 mg kg(-1) day(-1) with the rat and 563 mg kg(-1) day(-1) with mice. Neither species showed any evidence of embryotoxicity or teratogenicity. There was no evidence for reproductive toxicity with mice given up to 3% TEG in drinking water in a continuous breeding study. TEG did not produce mutagenic or clastogenic effects in the following in vitro genetic toxicology studies: Salmonella typhimurium reverse mutation test, SOS-chromotest in E. coli, CHO forward gene mutation test (HGPRT locus), CHO sister chromatid exchange test, and a chromosome aberration test with CHO cells. The use patterns suggest that exposure to TEG is mainly occupational, with limited exposures by consumers. Exposure is normally by skin and eye contact. Local and systemic adverse health effects by cutaneous exposure are likely not to occur, and eye contact will produce transient irritation without corneal injury. The very low vapor pressure of TEG makes it unlikely that significant vapor exposure will occur. Aerosol exposure is not a usual exposure mode, and acute aerosol exposures are unlikely to be harmful, although a peripheral sensory irritant effect may develop. However, repeated exposures to a TEG aerosol may result in respiratory tract irritation, with cough, shortness of breath and tightness of the chest. Recommended protective and precautionary measures include protective gloves, goggles or safety glasses and mechanical room ventilation. LC(50) data to various fish, aquatic invertebrates and algae, indicate that TEG is essentially nontoxic to aquatic organisms. Also, sustained exposure studies have demonstrated that TEG is of a low order of chronic aquatic toxicity. The bioconcentration potential, environmental hydrolysis, and photolysis rates are low, and soil mobility high. In the atmosphere TEG is degraded by reacting with photochemically produced hydroxyl radicals. These considerations indicate that the potential for ecotoxicological effects with TEG is low.

Mammalian toxicology overview and human risk assessment for sulfosulfuron

Sulfosulfuron is a low-use rate sulfonylurea herbicide. A review of the toxicity database for sulfosulfuron indicates that the molecule has a low order of acute toxicity. It is not genotoxic and is not a reproductive, developmental, or nervous system toxicant. There were no indications of endocrine disruption in any study performed with the molecule. The only findings considered to be an adverse effect in mammalian laboratory animals following prolonged subchronic or chronic exposure to sulfosulfuron were isolated to the urinary tract. These findings occurred in conjunction with findings of urolith formation following high-level chemical dosing, resulting in epithelial hyperplasia that, in a few cases, progressed to tumor formation. Mode-of-action information supports the conclusion that these tumors result from a non-genotoxic, threshold-based process that is well established and widely considered to be not relevant to humans. Based on its short-term, infrequent application pattern and very low use rate and crop residues, aggregate and cumulative risk assessments indicate that sulfosulfuron has substantial margins of exposure and does not represent a significant risk to human health.

Summary of safety studies conducted with synthetic lycopene

Lycopene belongs to the group of natural carotenoids, which are found in many fruits and vegetables, but predominantly in tomatoes and tomato-based products. This manuscript summarizes the safety of synthetic lycopene as a water-dispersible beadlet formulation containing antioxidants and includes acute and subchronic safety studies, reproductive studies, genotoxicity studies, metabolic studies, and exploratory studies on the hepatic uptake of lycopene. Lycopene has a low order of acute toxicity and no significant toxicity has been observed in rats treated with lycopene beadlet formulations in the diet at doses of up to 500 mg/kg bw/day for 14 weeks or 1000 mg/kg bw/day for 4 weeks. No teratogenic effects were noted in a rat two-generation study (1000 ppm in the diet) or in a teratology study in rats with 1000 mg/kg bw/day lycopene as beadlet formulations. Lycopene accumulates in hepatocytes and to a lesser extent in spleen. In short-term studies with synthetic lycopene, as a beadlet formulation, and natural source lycopene, as tomato concentrate, the accumulation of lycopene in the liver and the presence of pigment deposits in the hepatocytes were similar and neither was associated with any histopathological changes. The pigment deposits in hepatocytes are no longer present after approximately 13 weeks of depletion, demonstrating reversibility for this effect. Unformulated pure crystalline lycopene and lycopene as a 10% beadlet formulation are not genotoxic as determined in a comprehensive battery of tests, however, improperly stored, unformulated crystalline lycopene can degrade to mutagenic products if exposed to light and air. Lycopene is commercially available only in formulated forms, containing antioxidants, which prevent the degradation of lycopene and other excipients that provide for water dispersibility. In the animal studies, there is a large margin of safety based on the repeated dose safety and reproductive/teratology studies in rodents. In humans, there is a very long history of use with respect to dietary exposure, and even in the case of very high exposures from dietary sources, there is no indication of any significant adverse effects.

Update on the Development of HFC-245fa as a Liquid HFC Blowing Agent

Because of continuing environmental concerns about ozone depletion, regulatory mandates have been established that require the phaseout of compounds with any potential to deplete the ozone layer, including HCFC-141b. These regulations vary from country to country, but in the U.S., for example, HCFC-141b will be phased out in less than a decade. Although there are several potential options for replacement blowing agents, many applications will continue to require a liquid, non-flammable blowing agent designed to produce foams with low thermal conductivity using traditional processing techniques. The most promising class of materials to fill this need are liquid HFCs. AlliedSignal is committed to supplying a liquid HFC blowing agent to the foam industry. At the 1994 Polyurethane World Congress, AlliedSignal announced that HFC-245fa (1,1,1,3,3-pentafluoropropane) was our primary candidate for a liquid HFC third generation blowing agent to replace HCFC-141b. This molecule was selected after a rigorous screening process in which several hundred candidates were ranked using physical properties, flammability characteristics, performance as a blowing agent, economics, environmental acceptability, and anticipated toxicity as selection criteria. HFC-245fa was found to offer the optimum combination of these attributes. In order to fully qualify this or any other material as a foam blowing agent, however, much more extensive work is required in all these areas. Additionally, customer validation and feedback is critical at every step in the process to ensure commercial viability and ultimate acceptance in the rigid foam market. This paper provides an update on the continuing HFC-245fa development program being conducted by AlliedSignal. The physical, environmental, and flammability properties of HFC-245fa are reviewed. Of particular note is that the flammability of HFC-245fa has been extensively tested by several ASTM test methods and the product's non-flammability has been confirmed. An update of the toxicity testing program for HFC-245fa is given. Results to date are very encouraging. The acute testing program is nearly complete and the results suggest that this material has a very low order of acute toxicity. This acute testing, however, does not provide a guarantee of success in full-scale toxicity tests. Full scale toxicity testing of HFC-245fa in several repeated dose studies is scheduled to begin soon. An important property of any blowing agent is its stability, both thermal and chemical. HFC-245fa has previously been shown to exhibit excellent thermal stability up to 200°C neat and in the presence of water, aluminum, and/or stainless steel [1]. Further testing has been conducted to determine the thermal stability of HFC-245fa in the presence of cold rolled steel under a variety of conditions. HFC-245fa continues to show excellent thermal stability characteristics under a variety of conditions. Three aspects of chemical stability are discussed. The first is the stability of the blowing agent in the presence of other common polyurethane foam raw materials and blends. Related to this is the stability of formulated B components after extended storage periods as measured by changes in system reactivity over time. The third is the stability of the blowing agent during the foaming reaction as determined by measuring levels of decomposition products, if any, in the foam's cells. The results of our preliminary investigations in these three areas are very encouraging. A major difference between HFC-245fa and HCFC-141b is their boiling points, 59° F for HFC-245fa vs 89° F for HCFC-141b. The implications of the lower boiling point and correspondingly higher vapor pressure of HFC-245fa vs HCFC-141b in two important areas, storage/handling and foam properties have been previously discussed [1].

Industrial research on alternative fluorocarbons

Fluorocarbons containing chlorine or bromine have been associated with stratospheric ozone depletion and the search for suitable alternatives is progressing at an accelerated pace. The Program for Alternative Fluorocarbon Toxicity Testing (PAFT), an international group representing most of the world's CFC producers, has been conducting comprehensive toxicological evaluations on several possible replacements for current fire-extinguishing agents — 1,1-dichloro-2,2,2-trifluoroethane (HCFC-123), 1-chloro-1,2,2,2-tetrafluoroethane (HCFC-124), pentafluoroethane (HFC-125), and l-fluoro-2,2,2-trifluoroethane (HFC-134a). Results from short-term experimental studies showing a low order of acute toxicity, as well as results from longer-term toxicity studies on these replacements, will be discussed.

Toxicology update isoparaffinic hydrocarbons: A summary of physical properties, toxicity studies and human exposure data

The Isoparaffins covered in this manuscript are branched aliphatic hydrocarbons with a carbon skeleton length ranging from approximately C10 to C15. They are used in the manufacture of liquid imaging toners, paint formulations, charcoal lighter fluid, furniture polishes and floor clearners. Potential exposure exists in the petroleum, printing and paint industries. Isoparaffins have a very low order of acute toxicity, being practically non-toxic by oral, dermal and inhalation routes. However, aspiration of liquid isoparaffins into the lungs during oral ingestion could result in severe pulmonary injury. Dermally, isoparaffins have produced slight to moderate irritation in animals and humans under occluded patch conditions where evaporation cannot freely occur. However, they are not irritating in non-occluded tests, which are a more realistic simulation of human exposure. They have not been found to be sensitizers in guinea pig or human patch testing. However, occasional rare idiosyncratic sensitization reactions in humans have been reported. Instillation of isoparaffins into rabbit eyes produces only slight irritation. Several studies have evaluated sensory irritation in laboratory animals or odor or sensory response in humans. When evaluated by a standard procedure to assess upper airway irritation, isoparaffins did not produce sensory irritation in mice exposed to up to 400 ppm isoparaffin in air. Human volunteers were exposed for six hours to 100 ppm isoparaffin. The subjects were given a self-administered questionnaire to evaluate symptoms, which included dryness of the mucous membranes, loss of appetite, nausea, vomiting, diarrhea, fatigue, headache, dizziness, feeling of inebriation, visual disturbances, tremor, muscular weakness, impairment of coordination or paresthesia. No symptoms associated with solvent exposure were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

A Review of the Toxicology Profile of Rioprostil

The toxicity of rioprostil was extensively investigated. Studies in rodents, dogs and monkeys indicate a low order of acute toxicity. Oral subchronic and chronic toxicity studies in rats and dogs produce effects that would be expected based on the pharmacological activity of the compound. In reproduction studies with rioprostil, male and female fertility is unaffected in rats at doses up to 2.0 mg/kg/day and there is no evidence of embryotoxicity, fetotoxicity, or teratogenicity in rats at doses up to 1.7 mg/kg/day. In rabbits a maternally toxic dose (1.5 mg/kg) also increases resorptions, reduces fetal weight, and increases the incidence of malformations. Evaluation of 24-month carcinogenicity studies in mice and rats at oral doses up to 2.0 and 1.5 mg/kg/day, respectively, are in progress. Mutagenicity studies are negative.

Anti‐stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera

AbstractTwo new acylsterylglucosides, sitoindoside VII and sitoindoside VIII, were isolated from the roots of Withania somnifera Dun., and were screened for putative anti‐stress activity because the plant is widely regarded as the ‘Indian Ginseng’ by practitioners of the traditional Indian system of medicine. Since an acceptable paradigm of pharmacological tests for anti‐stress screening has yet to be evolved, a battery of tests were employed to delineate the activity of the test compounds.The total MeOH‐H2O (1:1) extractives of the roots of W. somnifera (SG‐1) and equimolecular combination of sitoindosides VII, VIII and withaferin‐A, a common withanolide, (SG‐2), exhibited significant anti‐stress activity in all the test parameters used. The two sitoindosides also produced per se anti‐stress activity, which was potentiated by withaferin‐A. A preliminary acute toxicity study indicated that the compounds have a low order of acute toxicity. The anti‐stress activity of SG‐1 and SG‐2 is consonant with the therapeutic use of W. somnifera in the Ayurveda, the Indian system of medicine.

ChemInform Abstract: (1,3‐DIALKYL‐5‐AMINO‐1H‐PYRAZOL‐4‐YL)ARYLMETHANONES. A SERIES OF NOVEL CENTRAL NERVOUS SYSTEM DEPRESSANTS

AbstractAusgehend von den Pyrazolen (I), (III) und (V) erhält man die Aminoderivate (II), die anticonvulsive und ZNS‐Wirkun besitzen.

(1,3-Dialkyl-5-amino-1H-pyrazol-4-yl)arylmethanones. A series of novel central nervous system depressants.

A series of novel (1,3-dialkyl-5-amino-1H-pyrazol-4-yl)arylmethanones was synthesized. Pharmacological evaluation of these compounds demonstrated central nervous system depressant activity, potential anticonvulsant properties, and a low order of acute toxicity. In addition, selected compounds showed potential antipsychotic effects. This report focuses on the synthesis and structure-activity relationships of these compounds. (5-Amino-1-ethyl-3-methyl-1H-pyrazol-4-yl)(2-chlorophenyl) methanone (21) was the most active compound against pentylenetetrazole-induced convulsions. (5-Amino-1,3-dimethyl-1H-pyrazol-4-yl)(3-chlorophenyl)methanone (4) also has a favorable anticonvulsant depression ratio. (5-Amino-1,3-dimethyl-1H-pyrazol-4-yl)(3-trifluoromethylphenyl)methan one (8), (5-amino-1,3-dimethyl-1H-pyrazol-4-yl)(3-thienyl)methanone (13), and (5-amino-3-ethyl-1-methyl-1H-pyrazol-4-yl)phenylmethanone (14) are very potent depressants. (5-Amino-1,3-dimethyl-1H-pyrazol-4-yl)(2-thienyl)methanone (12) possessed marked central depressant activity without anticonvulsant activity and without impairment of motor functioning. (5-Amino-1,3-dimethyl-1H-pyrazol-4-yl) (2-fluorophenyl)methanone (2) has a behavioral profile suggestive of antipsychotic activity and gave a positive Ames test result.

Acute and environmental toxicity studies with hexazinone

The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the enviroment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. Repeated doses (five oral doses per week for 2 weeks) of 300 mg/kg to rats produced slight weight loss in one of two replicate experiments. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. There were no alterations in livers from treated rabbits examined by light microscopy. No dermal sensitization was produced when concentrations of up to 50% were tested in guinea pigs. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats. In freshwater biota, the material had slight to low toxicity with 96-hr LC50 values being between 370 and 420 mg/liter in bluegill sunfish, between 320 and 420 mg/liter in rainbow trout, and 274 mg/liter in fathead minnows. The 48-hr LC50 in Daphnia magna was 152 ppm. In marine biota, similar low toxicity was indicated by a 48-hr EC50 of 320 to 450 ppm in eastern oysters, a 96-hr LC50 of 56 to 100 ppm in grass shrimp, and a 96-hr LC50 greater than 1000 ppm in fiddler crabs. Bobwhite quail were not killed by feeding of up to 10,000 ppm. When given to quail as a single oral dose by intubation, the LD50 value was 2258 mg/kg. Ducks survived feeding of 10,000 ppm indicating that the material has a low order of toxicity in water fowl and upland game birds. Hexazinone had a low order of acute toxicity when tested in mammals, freshwater and marine biota, and birds. The material is an eye irritant and should be handled carefully. Dermal irritancy, sensitization potential, and systemic toxicity are low.

Acute and Environmental Toxicity Studies with Hexazinone

Acute and Environmental Studies with Hexazinone. KENNEDY, G. L, JR. (1984). Fundam. Appl. Toxicol. 4, 603–611. The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. Repeated doses (five oral doses per week for 2 weeks) of 300 mg/kg to rats produced slight weight loss in one of two replicate experiments. In both studies, no gross or histologjc alterations were apparent Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. There were no alterations in livers from treated rabbits examined by light microscopy. No dermal sensitization was produced when concentrations of up to 50% were tested in guinea pigs. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats. In freshwater biota, the material had slight to low toxicity with 96-hr LC50 values being between 370 and 420 mg/liter in bluegill sunfish, between 320 and 420 mg/liter in rainbow trout, and 274 mg/liter in fathead minnows. The 48-hr LC50 in Daphnia magna was 152 ppm. In marine biota, similar low toxicity was indicated by a 48-hr EC50 of 320 to 540 ppm in eastern oysters, a 96-hr LC50 of 56 to 100 ppm in grass shrimp, and a 96-hr LC50 greater than 1000 ppm in fiddler crabs. Bobwhite quail were not killed by feeding of up to 10,000 ppm. When given to quail as a single oral dose by intubation, the LD50 value was 2258 mg/kg. Ducks survived feeding of 10,000 ppm indicating that the material has a low order of toxicity in water fowl and upland game birds. Hexazinone had a low order of acute toxicity when tested in mammals, freshwater and marine biota, and birds. The material is an eye irritant and should be handled carefully. Dermal irritancy, sensitization potential, and systemic toxicity are low.

Sorbistin, a new aminoglycoside antibiotic complex of bacterial origin. I. Production, isolation and properties.

A strain of a new Pseudomonas species produced the aminoglycoside antibiotic complex, sorbistin, which was separated by ion-exchange chromatography into three bio-active components A1, A2 and B, and two bio-inactive components C and D. Sorbistins A1, A2 and B showed moderate intrinsic activity against a wide range of bacterial species and inhibited most of the aminoglycoside-resistant organisms. Sorbistin A1 exhibited the highest activity among the three bio-active components. Sorbistins showed low order of acute toxicity in mice.

Toxicity studies with 5-bromo-3- sec-butyl-6-methyluracil

The herbicide, 5-bromo-3- sec-butyl-6-methyluracil (bromacil) exhibited a low order of acute toxicity as evaluated by oral, dermal, and inhalation studies in mammals and by fish and wildlife studies. Bromacil fed to pregnant New Zealand white rabbits on days 8–16 of gestation at dietary levels of 0, 50, and 250 ppm was not teratogenic. In a three-generation six-litter reproduction study with rats, a dietary level of 250 ppm had no adverse effects upon reproduction and lactation performance; no pathologic changes were observed in weanling pups of the F 3b generation. Rats of both sexes were fed nutritionally complete diets containing 0, 50, 250, and 1250 ppm bromacil for 2 yr. Except for a lower rate of weight gain, a slightly decreased food intake and a slightly lower food efficiency among the female rats that received 1250 ppm bromacil, there was no nutritional, clinical, hematologic, urinary, or biochemical evidence of toxicity, nor any evidence of carcinogenicity; there was, however, a suggestion of slight hyperplasia in the thyroids of animals given the highest dietary level. Beagle dogs of both sexes, 1–2 yr of age, fed nutritionally complete diets containing 0, 50, 250, and 1250 ppm bromacil for 2 yr, showed no nutritional, clinical, hematological, urinary, biochemical, or pathologic evidence of toxicity.

P-Hydroxybenzoic Acid Esters as Preservatives II.:Acute and Chronic Toxicity in Dogs, Rats, and Mice

The results of a study of the acute and chronic toxicity of p-hydroxybenzoic acid and the methyl, ethyl, propyl, and butyl esters in mice, rats, and dogs are presented. All of these compounds possess a low order of acute toxicity. The toxicity of the sodium salts appears to be a function of the length of the alkyl substituent, with the butyl ester about three times as toxic as the methyl ester. The main toxic effect is an acute myocardial depression accompanied by hypotension, but this is transient in nature and not cumulative. No evidence of blood damage or histological changes in tissues of treated animals was noted. In concentrations below 5 per cent, none of the esters produces any evidence of primary irritation when applied to the intact skin of man. From the results obtained, it may be concluded that the methyl, ethyl, and propyl esters of p-hydroxybenzoic acid may be used safely as preservatives in effective concentrations for foods and drugs.