Rod G. Gullberg

Guidelines for estimating the amount of alcohol consumed from a single measurement of blood alcohol concentration: re-evaluation of Widmark's equation.

This article deals with the pharmacokinetics of ethanol and the reliability of estimating the amount of alcohol ingested from a single measurement of a persons blood alcohol concentration (BAC). Blood alcohol curves were plotted for 108 male subjects after they drank various doses of ethanol (0.51-0.85 g/kg body weight). The rate of disappearance of ethanol from the blood (beta-slope) and the apparent volume of distribution of ethanol (Widmarks rho factor, rho) were calculated for each subject; the mean beta-slope was 13.3 mg/dl/h (SD = 2.0), and the mean rho factor was 0.689 l/kg (SD = 0.061). The value of beta increased slightly with increasing dose of alcohol (P < 0.05). The blood alcohol parameters beta and rho were negatively correlated (r = -0.135). The BACs measured at 2 h and 5 h post-drinking were used to estimate the amount of alcohol each subject had consumed according to the method proposed by Widmark [1]. The mean differences (estimated-actual) and the +/- 95% limits of agreement were -0.72 g (+/- 12), and 2.2 (+/- 15), for the 2 h and 5 h BAC values, respectively. A method based on error propagation was used to derive the 95% limits of uncertainty in the amount of alcohol ingested. On the basis of a single measurement of BAC, we could estimate the amount of alcohol ingested within +/- 20%.

The elimination rate of mouth alcohol: mathematical modeling and implications in breath alcohol analysis

Mouth alcohol, if present in high enough concentrations, can falsely bias the accurate measurement of end-expiratory breath alcohol. Mouth alcohol will be eliminated over time, however, and can be modeled with a single term decaying exponential of the form: B0e-kt + C. It is important, however, to determine the model and its parameters when alcohol is already present within the biologic system. Using three individuals as their own controls, mouth alcohol was administered both before and after alcohol consumption followed by breath alcohol analysis performed at approximately 0.5 min intervals. The results showed that both model parameters (B0 and k) are effected and that the asymptotic value (C) is reached much sooner when alcohol already exists in the end-expiratory breath. Considering only three individuals were involved, the forensic-science importance appears to be that, as the end-expiratory breath alcohol concentration increases, the time necessary for the mouth alcohol to decrease to unbiased levels is decreased. Fifteen min of observation time prior to breath alcohol analysis appears to be more than adequate at forensically relevant concentrations.

Differentiating new cannabis use from residual urinary cannabinoid excretion in chronic, daily cannabis users

AIMS To develop and validate empirically a mathematical model for identifying new cannabis use in chronic, daily cannabis smokers. DESIGN Models were based on urinary creatinine-normalized (CN) cannabinoid excretion in chronic cannabis smokers. SETTING For model development, participants resided on a secure research unit for 30 days. For model validation, participants were abstinent with daily observed urine specimens for 28 days. PARTICIPANTS A total of 48 (model development) and 67 (model validation) daily cannabis smokers were recruited. MEASUREMENTS All voided urine was collected and analyzed for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) by gas chromatography-mass spectrometry (GCMS; limit of quantification 2.5 ng/ml) and creatinine (mg/ml). Urine THCCOOH was normalized to creatinine, yielding ng/mg CN-THCCOOH concentrations. Urine concentration ratios were determined from 123,513 specimen pairs collected 2-30 days apart. FINDINGS A mono-exponential model (with two parameters, initial urine specimen CN-THCCOOH concentration and time between specimens), based on the Marquardt-Levenberg algorithm, provided a reasonable data fit. Prediction intervals with varying probability levels (80, 90, 95, 99%) provide upper ratio limits for each urine specimen pair. Ratios above these limits suggest cannabis re-use. Disproportionate numbers of ratios were higher than expected for some participants, prompting development of two additional rules that avoid misidentification of re-use in participants with unusual CN-THCCOOH excretion patterns. CONCLUSIONS For the first time, a validated model is available to aid in the differentiation of new cannabis use from residual creatinine-normalized 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (CN-THCCOOH) excretion in chronic, daily cannabis users. These models are valuable for clinicians, toxicologists and drug treatment staff and work-place, military and criminal justice drug-testing programs.

Breath alcohol measurement variability associated with different instrumentation and protocols

Breath alcohol measurement has variability resulting from instrumental, procedural and biological components. Reliable estimates of the standard deviation (S.D.) are necessary for calculating uncertainty in the form of confidence intervals. These estimates are concentration dependant and can be obtained from models derived from duplicate breath test data. Duplicate data from four state jurisdictions (Alabama using the Drager 7110, Minnesota using the Intoxilyzer 5000, Washington using the BAC Datamaster and Wisconsin using the Intoximeter EC/IR) were analyzed to derive predictive models for standard deviation as a function of concentration. All jurisdiction/instrument combinations yielded forensically acceptable variation while showing a general linear increase in standard deviation with concentration. This is consistent with a multiplicative error model. Jurisdictions using the same instruments but not performing duplicate analyses could also employ the straightforward models derived here to estimate standard deviations for their measurement results.

New Zealand's Breath and Blood Alcohol Testing Programs: Further data analysis and forensic implications

Paired blood and breath alcohol concentrations (BAC, in g/dL, and BrAC, in g/210 L), were determined for 11,837 drivers apprehended by the New Zealand Police. For each driver, duplicate BAC measurements were made using headspace gas chromatography and duplicate BrAC measurements were made with either Intoxilyzer 5000, Seres 679T or Seres 679ENZ Ethylometre infrared analysers. The variability of differences between duplicate results is described in detail, as well as the variability of differences between the paired BrAC and BAC results. The mean delay between breath and blood sampling was 0.73 h, ranging from 0.17 to 3.1 8h. BAC values at the time of breath testing were estimated by adjusting BAC results using an assumed blood alcohol clearance rate. The paired BrAC and time-adjusted BAC results were analysed with the aim of estimating the proportion of false-positive BrAC results, using the time-adjusted BAC results as references. When BAC results were not time-adjusted, the false-positive rate (BrAC>BAC) was 31.3% but after time-adjustment using 0.019 g/dL/h as the blood alcohol clearance rate, the false-positive rate was only 2.8%. However, harmful false-positives (defined as cases where BrAC>0.1 g/210L, while BAC< or =0.1g/dL) occurred at a rate of only 0.14%. When the lower of duplicate breath test results were used as the evidential results instead of the means, the harmful false-positive rate dropped to 0.04%.

Estimating the measurement uncertainty in forensic blood alcohol analysis.

For many reasons, forensic toxicologists are being asked to determine and report their measurement uncertainty in blood alcohol analysis. While understood conceptually, the elements and computations involved in determining measurement uncertainty are generally foreign to most forensic toxicologists. Several established and well-documented methods are available to determine and report the uncertainty in blood alcohol measurement. A straightforward bottom-up approach is presented that includes: (1) specifying the measurand, (2) identifying the major components of uncertainty, (3) quantifying the components, (4) statistically combining the components and (5) reporting the results. A hypothetical example is presented that employs reasonable estimates for forensic blood alcohol analysis assuming headspace gas chromatography. These computations are easily employed in spreadsheet programs as well. Determining and reporting measurement uncertainty is an important element in establishing fitness-for-purpose. Indeed, the demand for such computations and information from the forensic toxicologist will continue to increase.

REPRODUCIBILITY OF WITHIN-SUBJECT BREATH ALCOHOL ANALYSIS

Random samples from normal distributions are an important assumption for many statistical methods. The present study evaluates this assumption with regard to quantitative breath alcohol analyses. Eight individuals (six male and two female) consumed alcoholic beverages and subsequently provided replicate (n ranging from 22 to 69) breath samples to an infrared breath alcohol instrument within short time intervals. The serially collected data were treated with several descriptive and inferential methods. Descriptive results among the eight individuals included: mean 0.0420–0.1175 g/210L, SD 0.0008–0.0045 g/210L and CV: 1.9%–4.7%. Statistical tests for normality showed seven of the distributions to be reasonably normal (p ≥ 0.25) and the other marginal (p = 0.051). A test for runs about the median showed random results (p ≥ 0.10) for four individuals and non-random (p ≤ 0.01) for the other four. The results suggest an individuals breath alcohol measurement, when appropriately collected and analysed, should be considered a random sample from a normal within-subject distribution. The existing variability in breath alcohol analysis, due largely to biological and sampling considerations, is acceptably minimized to warrant forensic application.

Repeatability of replicate breath alcohol measurements collected in short time intervals

The effect of short time interval sampling between replicate breath alcohol samples has been investigated. The results from 10 samples, which were collected approximately one minute apart from eight individuals and approximately 20 seconds apart from one individual, were evaluated by simple linear regression. The regression coefficient (slope) and its standard error were evaluated for the presence of any trend in alcohol depletion. Other statistical analyses were also included in this assessment. All nine subjects had linear regression coefficients for the end-expiratory results that were not significantly different from zero (P > 0.05). In view of the respiratory physiology, there does not appear to be any measurable depletion of breath alcohol concentration due to sampling intervals as short as one minute.

Isopropanol interference with breath alcohol analysis: a case report.

The presence of interfering substances, particularly acetone, has historically been a concern in the forensic measurement of ethanol in human breath. Although modern infrared instruments employ methods for distinguishing between ethanol and acetone, false-positive interferant results can arise from instrumental or procedural problems. The case described gives the analytical results of an individual arrested for driving while intoxicated and subsequently providing breath samples in two different BAC Verifier Datamaster infrared breath alcohol instruments. The instruments recorded ethanol results ranging from 0.09 to 0.17 g/210 L with corresponding interferant results of 0.02 to 0.06 g/210 L over approximately three hours. Breath and venous blood specimens collected later were analyzed by gas chromatography and revealed in the blood: isopropanol 0.023 g/100 mL, acetone 0.057 g/100 mL and ethanol 0.076g/100 mL. Qualitative analysis of the breath sample by GCMS also showed the presence of all three compounds. This individual had apparently consumed both ethanol and isopropanol with acetone resulting from the metabolism of isopropanol. An important observation is that the breath test instruments detected the interfering substances on each breath sample and yet they did not show tendencies to report false interferences when compared with statewide interferant data.

Factors contributing to the variability observed in duplicate forensic breath alcohol measurement

Several factors contribute to the variability observed among repeated measurements of breath alcohol concentration. Identifying these factors and the magnitude of their contribution is the focus of this study. Large breath alcohol data sets consisting of duplicate test results from drivers arrested for driving while intoxicated were obtained from four jurisdictions: Sweden, Alabama, New Jersey and Washington State. The absolute difference between duplicate results were fitted to a multivariate linear regression model which included the following predictor variables: mean breath alcohol concentration, absolute exhalation time difference between repeated measurements, absolute exhalation volume difference, gender and age. In all data sets considered here, the breath alcohol concentration was the most statistically and practically significant predictor of absolute difference between the duplicate results. The next two most important predictors to enter models for all jurisdictions were exhalation volume difference and exhalation time difference. The maximum multivariate R² for any jurisdiction, however, was only 0.24, suggesting that other factors not considered here may be of importance. Two predictors over which the subject would have some influence included exhalation time and volume. When these were set at values expected to have maximum impact, the effect on duplicate test differences was very small, 0.008 g/210 L or less in all jurisdictions, indicating that subject manipulation of exhalation time and volume would have at most a very small systematic effect on estimated breath alcohol concentration. This study presents multivariate models useful for identifying the impact of five variables that may influence breath test variability.