Handling of inspired vaporized ethanol in the airways and lungs (with comments on forensic aspects)

Kruhøffer, P.

doi:10.1016/0379-0738(83)90085-3

Cited by 16 publications

(8 citation statements)

References 5 publications

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“…In the case of ethylene oxide, the PBPK model created by Fennell and Brown (2001) accounted for a reduced uptake by decreasing alveolar ventilation to 43%, agreeing with experimental evidence that uptake in rats may be as low as 40% (Johanson & Filser, 1992). For ethanol, there is experimental evidence that a large fraction gets deposited in the airway lining (Kruhoffer, 1983). Therefore, Pastino et al (1997) reduced the inhaled ethanol fraction concentration to 65% to account for absorption in the upper airways in their PBPK model.…”

Section: Chemically Induced Ventilation Changessupporting

confidence: 51%

Incorporation of Acute Dynamic Ventilation Changes into a Standardized Physiologically Based Pharmacokinetic Model

Stuhmiller

2007

Inhalation Toxicology

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A seven-compartment physiologically based pharmacokinetic (PBPK) model incorporating a dynamic ventilation response has been developed to predict normalized internal dose from inhalation exposure to a large range of volatile gases. The model uses a common set of physiologic parameters, including standardized ventilation rates and cardiac outputs for rat and human. This standardized model is validated against experimentally measured blood and tissue concentrations for 21 gases. For each of these gases, body-mass-normalized critical internal dose (blood concentration) is established, as calculated using exposure concentration and time duration specified by the lowest observed adverse effect level (LOAEL) or the acute exposure guideline level (AEGL). The dynamic ventilation changes are obtained by combining the standardized PBPK model with the Toxic Gas Assessment Software 2.0 (TGAS-2), a validated acute ventilation response model. The combined TGAS-2P model provides a coupled, transient ventilation and pharmacokinetic response that predicts body mass normalized internal dose that is correlated with deleterious outcomes. The importance of ventilation in pharmacokinetics is illustrated in a simulation of the introduction of Halon 1301 into an environment of fire gases.

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Section: Chemically Induced Ventilation Changessupporting

confidence: 51%

Incorporation of Acute Dynamic Ventilation Changes into a Standardized Physiologically Based Pharmacokinetic Model

Stuhmiller

2007

Inhalation Toxicology

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“…It is generally allowed that, on nondamaged skin, about 1% of the dose of ethanol initially placed on the surface actually penetrates the skin barrier. The amount is thus negligible when compared to pulmonary absorption, which is estimated at 60% [14, 15]. …”

Section: Discussionmentioning

confidence: 99%

Short Communication: Is Ethanol-Based Hand Sanitizer Involved in Acute Pancreatitis after Excessive Disinfection?—An Evaluation with the Use of PBPK Model

Huynh-Delerme

Artigou

Bodin

et al. 2012

Journal of Toxicology

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An occupational physician reported to the French Health Products Safety Agency (Afssaps) a case of adverse effect of acute pancreatitis (AP) in a teaching nurse, after multiple demonstrations with ethanol-based hand sanitizers (EBHSs) used in a classroom with defective mechanical ventilation. It was suggested by the occupational physician that the exposure to ethanol may have produced a significant blood ethanol concentration and subsequently the AP. In order to verify if the confinement situation due to defective mechanical ventilation could increase the systemic exposure to ethanol via inhalation route, a physiologically based pharmacokinetic (PBPK) modeling was used to predict ethanol blood levels. Under the worst case scenario, the simulation by PBPK modeling showed that the maximum blood ethanol concentration which can be predicted of 5.9 mg/l is of the same order of magnitude to endogenous ethanol concentration (mean = 1.1 mg/L; median = 0.4 mg/L; range = 0–35 mg/L) in nondrinker humans (Al-Awadhi et al., 2004). The present study does not support the likelihood that EBHS leads to an increase in systemic ethanol concentration high enough to provoke an acute pancreatitis.

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“…Mangione (1985) observed that inhalation of vapors of ethanol during use of rubbing alcohol can result in sufficient absorption to result in alcohol intoxication in children. Kruhoffer (1983) studied the rate of uptake of ethanol from prolonged periods of inspiration of air containing ethanol at a constant concentration of 10 to 12 mg/L (about 6000 ppm) in adult, male human subjects. The study indicated that, when ethanol is absent from the systemic blood, prolonged inspiration of ethanol-containing air results in absorption of 55% of the inspired ethanol and return of remainder with the expired air.…”

Section: Inhalationmentioning

confidence: 99%

Final Report of the Safety Assessment of Alcohol Denat., Including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the Denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate1

2008

Int J Toxicol

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Alcohol Denat. is the generic term used by the cosmetics industry to describe denatured alcohol. Alcohol Denat. and various specially denatured (SD) alcohols are used as cosmetic ingredients in a wide variety of products. Many denaturants have been previously considered, on an individual basis, as cosmetic ingredients by the Cosmetic Ingredient Review (CIR) Expert Panel, whereas others, including Brucine and Brucine Sulfate, Denatonium Benzoate, and Quassin, have not previously been evaluated. Quassin is a bitter alkaloid obtained from the wood of Quassia amara. Quassin has been used as an insect antifeedant and insecticide and several studies demonstrate its effectiveness. At oral doses up to 1000 mg/kg using rats, Quassin was not toxic in acute and short-term tests, but some reversible piloerection, decrease in motor activity, and a partial loss of righting reflex were found in mice at 500 mg/kg. At 1000 mg/kg given intraperitoneally (i.p.), all mice died within 24 h of receiving treatment. In a cytotoxicity test with brine shrimp, 1 mg/ml of Quassin did not possess any cytotoxic or antiplasmodial activity. Quassin administered to rat Leydig cells in vitro at concentrations of 5-25 ng/ml inhibited both the basal and luteinizing hormone (LH)-stimulated testosterone secretion in a dose-related fashion. Quassin at doses up to 2.0 g/kg in drinking water using rats produced no significant effect on the body weights, but the mean weights of the testes, seminal vesicles, and epididymides were significantly reduced, and the weights of the anterior pituitary glands were significantly increased. The sperm counts and levels of LH, follicle-stimulating hormone (FSH), and testosterone were significantly lower in groups treated with Quassin. Brucine is a derivative of 2-hydroxystrychnine. Swiss-Webster mice given Brucine base, 30 ml/kg, had an acute oral LD(50) of 150 mg/kg, with central nervous system depression followed by convulsions and seizures in some cases. In those animals that died, respiratory arrest was the cause. The acute i.p. LD(50) for 15 ml/kg of Brucine base was 62.0 mg/kg, with central nervous system depression prior to the onset of convulsions, just as with oral Brucine. The acute intravenous (i.v.) LD(50) was 12.0 mg/kg. Brucine was nonmutagenic in an Ames assay at levels up to 6666 mu g/plate, with and without metabolic activation. In a repeat-insult patch test, for a hair care product containing 47% SD Alcohol 40 (95%), it was reported that Brucine Sulfate may be considered a nonprimary irritant and a nonprimary sensitizer. Three different sunscreen products (35% SD Alcohol 40-B, 72.4% SD Alcohol 40, and 74.5% SD Alcohol 40) did not show any signs of photoallergy in human subjects. Also, these three formulas did not exhibit any evidence of phototoxicity in humans. Denatonium Benzoate is a bitter substance detectable at a concentration of 10 ppb, discernibly bitter at 50 ppb, and unpleasantly bitter at 10 ppm. The distribution of topically applied lidocaine, a topical anesthetic chemically related to Den...

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Handling of inspired vaporized ethanol in the airways and lungs (with comments on forensic aspects)

Cited by 16 publications

References 5 publications

Incorporation of Acute Dynamic Ventilation Changes into a Standardized Physiologically Based Pharmacokinetic Model

Incorporation of Acute Dynamic Ventilation Changes into a Standardized Physiologically Based Pharmacokinetic Model

Short Communication: Is Ethanol-Based Hand Sanitizer Involved in Acute Pancreatitis after Excessive Disinfection?—An Evaluation with the Use of PBPK Model

Final Report of the Safety Assessment of Alcohol Denat., Including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the Denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate1

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