A comprehensive evaluation of the toxicology resulting from laser-generated ventilation holes in cigarette filters.

CONTEXT: Recent technological advances allow ventilation holes in (or adjacent to) cigarette filters to be produced using lasers instead of using the mechanical procedures of earlier techniques. OBJECTIVE: Analytical chemistry can be used to compare the composition of mainstream smoke from experimental cigarettes having filters with mechanically produced ventilation holes to that of cigarettes with ventilation holes that were produced using laser technology. MATERIALS AND METHODS: Established procedures were used to analyze the smoke composition of 38 constituents of mainstream smoke generated using standard conditions. RESULTS: There were no differences between the smoke composition of cigarettes with filter ventilation holes that were produced mechanically or through use of laser technology. CONCLUSION: The two methods for producing ventilation holes in cigarette filters are equivalent in terms of resulting mainstream smoke chemistry, at two quite different filter ventilation percentages.

A safety trial of high dose glyceryl triacetate for Canavan disease.

Canavan disease (CD MIM#271900) is a rare autosomal recessive neurodegenerative disorder presenting in early infancy. The course of the disease is variable, but it is always fatal. CD is caused by mutations in the ASPA gene, which codes for the enzyme aspartoacylase (ASPA), which breaks down N-acetylaspartate (NAA) to acetate and aspartic acid. The lack of NAA-degrading enzyme activity leads to excess accumulation of NAA in the brain and deficiency of acetate, which is necessary for myelin lipid synthesis. Glyceryltriacetate (GTA) is a short-chain triglyceride with three acetate moieties on a glycerol backbone and has proven an effective acetate precursor. Intragastric administration of GTA to tremor mice results in greatly increased brain acetate levels, and improved motor functions. GTA given to infants with CD at a low dose (up to 0.25 g/kg/d) resulted in no improvement in their clinical status, but also no detectable toxicity. We present for the first time the safety profile of high dose GTA (4.5 g/kg/d) in 2 patients with CD. We treated 2 infants with CD at ages 8 months and 1 year with high dose GTA, for 4.5 and 6 months respectively. No significant side effects and no toxicity were observed. Although the treatment resulted in no motor improvement, it was well tolerated. The lack of clinical improvement might be explained mainly by the late onset of treatment, when significant brain damage was already present. Further larger studies of CD patients below age 3 months are required in order to test the long-term efficacy of this drug.

Final report on the safety assessment of triacetin.

Triacetin, also known as Glyceryl Triacetate, is reported to function as a cosmetic biocide, plasticizer, and solvent in cosmetic formulations, at concentrations ranging from 0.8% to 4.0%. It is a commonly used carrier for flavors and fragrances. Triacetin was affirmed as a generally recognized as safe (GRAS) human food ingredient by the Food and Drug Administration (FDA). Triacetin was not toxic to animals in acute oral or dermal exposures, nor was it toxic in short-term inhalation or parenteral studies, and subchronic feeding and inhalation studies. Triacetin was, at most, slightly irritating to guinea pig skin. However, in one study, it caused erythema, slight edema, alopecia, and desquamation, and did cause some irritation in rabbit eyes. Triacetin was not sensitizing in guinea pigs. Triacetin was not an irritant or a sensitizer in a clinical maximization study, and only very mild reactions were seen in a Duhring-chamber test using a 50% dilution. In humans, Triacetin reportedly has caused ocular irritation but no injury. Triacetin was not mutagenic. Although there were no available reproductive and developmental toxicity data, Triacetin was quickly metabolized to glycerol and acetic acid and these chemicals were not developmental toxins. Reports of 1,2-glyceryl diesters, which may be present in Triacetin, affecting cell growth and proliferation raised the possibility of hyperplasia and/or tumor promotion. The Cosmetic Ingredient Review (CIR) Expert Panel concluded, however, that the effects of 1,2-glyceryl diesters on cell growth and proliferation require longer ester chains on the glycerin backbone than are present when acetic acid is esterified with glycerin, as in Triacetin. On the basis of the available information, the CIR Expert Panel concluded that Triacetin is safe as used in cosmetic formulations.

Triacetin: a potential parenteral nutrient.

UNLABELLED: Triacetin, the water-soluble triglyceride of acetate, was infused in mongrel dogs at isocaloric (N = 6) or hypercaloric (approximately 1.5 REE, N = 7) rates in mongrel dogs for 3 hr. Ketone body and glucose production rates were quantified with [13C2] acetoacetate and [3H]glucose, respectively. Four additional animals were infused with glycerol to serve as controls for the hypercaloric triacetin infusion. Energy expenditure was determined in the isocaloric experiments. RESULTS: no evidence of acute toxicity was observed during triacetin infusion at either rate. Plasma acetate concentrations increased from basal levels to approximately 1 and approximately 13 mmol/liter in the isocaloric and hypercaloric experiments, respectively. Plasma lactate and pyruvate concentrations decreased dramatically after 30 min of both isocaloric and hypercaloric triacetin infusions. Glucose production rates did not increase in either group, but glucose clearance decreased significantly in both groups (p less than 0.05) over the last hour of triacetin infusion. Plasma ketone body concentrations increased from 1.4 to 3.5 and 1.8 to 13.5 mumol/kg.min, respectively, during isocaloric and hypercaloric triacetin infusion. Resting energy expenditure increased from 3.0 +/- 0.3 to 4.0 +/- 0.5 kcal/kg.hr during isocaloric triacetin infusion (p less than 0.05). These studies indicate that triacetin can be administered to dogs at high rates without overt toxicity. The decrease in glucose clearance may represent competition between carbohydrate (glucose) and lipid (acetate). Triacetin infusion resulted in significant increases in ketone body production and concentration. These preliminary data indicate that triacetin may have a future role as a parenteral nutrient, and that further studies of its use are warranted.

A new parenteral emulsion for the administration of taxol.

Taxol (NSC-125973) is a poorly soluble plant product that exhibits excellent antimitotic properties. This study involves the development of a new formulation for taxol. The stability of taxol in a 50% triacetin emulsion as well as possible methods of intravenous administration of this dosage form was examined. A stable emulsion was found at taxol concentrations of 10 and 15 mg/ml of emulsion. The 50% triacetin emulsion showed an intravenous LD50 of 1.2 ml/kg in Swiss-Webster mice. The 10 mg/ml taxol formulation was demonstrated to be stable upon addition to 5% dextrose iv fluids provided that small packing systems were used. The taxol-triacetin emulsion can also be intravenously injected at various rates, and it may prove to be a useful formulation for taxol.

[Comparative toxicity of triacetin and diethylene glycol diacetate]. / Sravnitelna toksichnost na triatsetin s dietilenglikoldiatsetat.

The approximative lethal dose of triacetin and diethylene glycole acetate is determined after the method of Deihmann and Leblanc. Experiments are conducted on white rats to establish the acute and subacute oral, dermal and inhalatory toxicity of the two substances. Changes in weight, liver and kidneys weight coefficient, hematopoiesis and hepatic function (biochemical and pathomorphological), as well as the stimulating effect on mucosa and skin are studied. The results of the study show a weak stimulating action on mucosa and skin, and insignificant cumulation. Emphasis is laid on the functional character of changes in the values of some enzymes -- alkaline phosphatase, cytochrome oxidase, cholinesterase -- and of the pathomorphologically established parenchymatous dystrophy. Presumably, it is a matter of changes more strongly manifested in imported triacetin. The conclusion is reached that imported triacetin may be substituted for lokally produced diethylene glycoldiacetate which proves to be with a lower acute and subacute toxicity.

Development of a toxicity evaluation program for dental materials and products. II. Screening for systemic toxicity.

A series of systemic toxicity tests for various types of compounds are presented with illustrative data and discussed in regard to their relevance as potential screening tests for dental compounds and products. In developing and marketing a new dental material, it is important not only to ensure safety for the patient but also for the dentist, dental assistant, and laboratory worker who routinely handles and uses the product. Data are presented on a number of commercially available dental products as well as various chemical entities, which were tested by one or more of the methods described.