Alan Wayne Jones

Comparison of ethanol concentrations in venous blood and end-expired breath during a controlled drinking study

Concentration-time profiles of ethanol were determined for venous whole blood and end-expired breath during a controlled drinking experiment in which healthy men (n=9) and women (n=9) drank 0.40-0.65 g ethanol per kg body weight in 20-30 min. Specimens of blood and breath were obtained for analysis of ethanol starting at 50-60 min post-dosing and then every 30-60 min for 3-6 h. This protocol furnished 130 blood-breath pairs for statistical evaluation. Blood-ethanol concentration (BAC, mg/g) was determined by headspace gas chromatography and breath-ethanol concentration (BrAC, mg/2l) was determined with a quantitative infrared analyzer (Intoxilyzer 5000S), which is the instrument currently used in Sweden for legal purposes. In 18 instances the Intoxilyzer 5000S gave readings of 0.00 mg/2l whereas the actual BAC was 0.08 mg/g on average (range 0.04-0.15 mg/g). The remaining 112 blood- and breath-alcohol measurements were highly correlated (r=0.97) and the regression relationship was BAC=0.10+0.91BrAC and the residual standard deviation (S.D.) was 0.042 mg/g (8.4%). The slope (0.91+/-0.0217) differed significantly from unity being 9% low and the intercept (0.10+/-0.0101) deviated from zero (t=10.2, P<0.001), indicating the presence of both proportional and constant bias, respectively. The mean bias (BAC - BrAC) was 0.068 mg/g and the 95% limits of agreement were -0.021 and 0.156 mg/g. The average BAC/BrAC ratio was 2448+/-540 (+/-S.D.) with a median of 2351 and 2.5th and 97.5th percentiles of 1836 and 4082. We found no significant gender-related differences in BAC/BrAC ratios, being 2553+/-576 for men and 2417+/-494 for women (t=1.34, P>0.05). The mean rate of ethanol disappearance from blood was 0.157+/-0.021 mg/(g per hour), which was very close to the elimination rate from breath of 0.161+/-0.021 mg/(2l per hour) (P>0.05). Breath-test results obtained with Intoxilyzer 5000S (mg/2l) were generally less than the coexisting concentrations of ethanol in venous blood (mg/g), which gives an advantage to the suspect who provides breath compared with blood in cases close to a threshold alcohol limit.

Evidence-based survey of the elimination rates of ethanol from blood with applications in forensic casework.

Reliable information about the elimination rate of alcohol (ethanol) from blood is often needed in forensic science and legal medicine when alcohol-related crimes, such as drunken driving or drug-related sexual assault are investigated. A blood sample for forensic analysis might not be taken until several hours after an offence was committed. The courts usually want to know the suspects blood-alcohol concentration (BAC) at some earlier time, such as the time of driving. Making these back calculations or retrograde extrapolations of BAC in criminal cases has many proponents and critics. Ethanol is eliminated from the body mainly by oxidative metabolism in the liver by Class I isoenzymes of alcohol dehydrogenase (ADH). Ethanol is an example of a drug for which the Michaelis-Menten pharmacokinetic model applies and the Michaelis constant (k(m)) for Class I ADH is at a BAC of 2-10mg/100mL. This means that the enzyme is saturated with substrate after the first few drinks and that zero-order kinetics is adequate to describe the declining phase of the BAC profile in most forensic situations (BAC>20mg/100mL). After drinking on an empty stomach, the elimination rate of ethanol from blood falls within the range 10-15 mg/100mL/h. In non-fasted subjects the rate of elimination tends to be in the range 15-20mg/100mL/h. In alcoholics during detoxification, because activity of microsomal enzyme (CYP2E1) is boosted, the ethanol elimination rate might be 25-35 mg/100mL/h. The slope of the BAC declining phase is slightly steeper in women compared with men, which seems to be related to gender differences in liver weight in relation to lean body mass. The present evidence-based review suggests that the physiological range of ethanol elimination rates from blood is from 10 to 35 mg/100mL/h. In moderate drinkers 15 mg/100mL/h remains a good average value for the population, whereas in apprehended drivers 19 mg/100mL/h is more appropriate, since many of these individuals are binge drinkers or alcoholics. In preparing this article, a large number of peer-reviewed publications were scrutinized. Only those meeting certain standards in experimental design, dose of alcohol and blood-sampling protocol were used. The results presented can hopefully serve as best-practice guidelines when questions arise in criminal and civil litigation about the elimination rate of ethanol from blood in humans.

Food-induced lowering of blood-ethanol profiles and increased rate of elimination immediately after a meal

In a two-part crossover study, ten healthy men drank a moderate dose of ethanol (0.80 g/kg) in the morning after an overnight fast or immediately after breakfast. The breakfast consisted of orange juice (150 mL), fruit yogurt (250 mL), two cheese sandwiches, one boiled egg, and one cup of coffee with milk and sugar. Ethanol was determined in venous blood at various times after the start of drinking by headspace gas chromatography. All subjects felt less intoxicated when alcohol was ingested after breakfast compared with drinking on an empty stomach. The peak BAC (+/- SD) was 67 +/- 9.5 mg/dL (ethanol + food) compared with 104 +/- 16.5 mg/dL when the drinking occurred after an overnight fast (P < 0.001). The mean area under the alcohol concentration-time profile (0-->6h) was 398 +/- 56 mg/dL x h in the fasting state compared with 241 +/- 34 mg/dL x h when subjects drank alcohol after the meal (P < 0.001). The time required to metabolize the dose of ethanol was approximately two hours shorter after the subjects had eaten breakfast. These results suggest that food in the stomach before drinking not only leads to a lowering of the peak BAC and diminishes the feelings of intoxication, but also boosts the rate of ethanol metabolism. A food-induced increase in the rate of disposal of ethanol was also confirmed when subjects ate a meal 5 h after drinking, that is, when the postabsorptive phase of ethanol metabolism was well established. The mean rate of disappearance of alcohol from blood was increased by between 36 and 50%.

Variability of the Blood/Breath Alcohol Ratio in Drinking Drivers

The ratio of blood-alcohol concentration (BAC) to breath-alcohol concentration (BrAC) was determined for 799 individuals apprehended for driving under the influence of alcohol (DUI) in Sweden. The BrAC was determined with an infrared analyzer (Intoxilyzer 5000S) and venous BAC was measured by headspace gas chromatography. The blood samples were always taken after the breath tests were made and the average time delay was 30 +/- 12 min (+/- SD), spanning from 6 to 60 min. The blood/breath ratios of alcohol decreased as the time between sampling blood and breath increased (F = 15.4, p < 0.001), being 2337 +/- 183 (6 to 15 min), 2302 +/- 202 (16 to 30 min), 2226 +/- 229 (31 to 45 min), and 2170 +/- 225 (46 to 60 min). When the BAC was corrected for the metabolism of alcohol at a rate of 0.019 g%/h, the mean blood/breath ratios were 2395 +/- 193 (6 to 15 min), 2416 +/- 211 (16 to 30 min), 2406 +/- 223 (31 to 45 min), and 2407 +/- 210 (45 to 60 min); no significant differences (F = 0.197, p > 0.05). The overall mean time-adjusted blood/breath ratio (+/- SD) was 2407 +/- 213 and the 95% limits of agreement (LOA) were 1981 and 2833. During 1992, 1993, and 1994, the mean blood/breath ratios of alcohol were remarkably constant, being 2409 +/- 288, 2407 +/- 206, and 2421 +/- 235, respectively, and the values were not significantly influenced by the persons age, gender, or blood-alcohol content. In 34 individuals (4.3%), the blood/breath ratio was less than 2100 after compensating for metabolism of alcohol between the times of sampling blood and breath. This compares with 156 individuals (19.6%) having a blood/breath ratio less than 2100:1 without making any correction for the metabolism of alcohol.

Five-year update on the occurrence of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes in Sweden

According to statistics provided by the Swedish National Road Administration (Vägverket), a total of 1403 drivers were killed in road-traffic crashes in Sweden between 2003 and 2007. Forensic autopsies were performed in approximately 97% of all deaths and specimens of blood and urine were sent for toxicological analysis. In 60% of cases (N=835) the toxicology results were negative and 83% of these victims were men. The blood-alcohol concentration (BAC) was above the legal limit for driving (>0.2g/L) in 22% of cases (N=315) at mean, median and highest concentrations of 1.7 g/L, 1.7 g/L and 4.9 g/L, respectively. The proportions of male to female drivers with BAC>0.2g/L were 93% vs 7% compared with 83% vs 17% for those with drugs other than alcohol in blood. Drivers with a punishable BAC were over-represented in single vehicle crashes compared with multiple vehicle crashes (67% vs 33%). The opposite held for drivers who had taken a prescription drug (39% vs 61%) and also for drug-negative cases (31% vs 69%). Drugs other than alcohol were identified in 253 cases (18%); illicit drugs only in 39 cases (2.8%), both licit and illicit in 28 cases (2.0%) and in 186 cases (13.3%) one or more therapeutic drugs were present. Amphetamine was the most common illicit drug identified at mean, median and highest concentrations of 1.5mg/L, 1.1mg/L and 5.0mg/L, respectively (N=39). Blood specimens contained a wide spectrum of pharmaceutical products (mean 2.4 drugs/person), comprising sedative-hypnotics (N=93), opiates/opioids (N=69) as well non-scheduled substances, such as paracetamol (N=78) and antidepressants (N=93). The concentrations of these substances in blood were mostly in the therapeutic range. Despite an appreciable increase (12-fold) in number of arrests made by the police for drug-impaired driving after a zero-tolerance law was introduced (July 1999), alcohol still remains the psychoactive substance most frequently identified in the blood of drivers killed in road-traffic crashes.

Driving under the influence of cannabis: a 10-year study of age and gender differences in the concentrations of tetrahydrocannabinol in blood

BACKGROUND Delta(9)-Tetrahydrocannabinol (THC) is the major psychoactive constituent of cannabis and its various preparations. Increasing use of cannabis for recreational purposes has created a problem for road-traffic safety. This paper compares age, gender and the concentrations of THC in blood of individuals apprehended for driving under the influence of drugs (DUID) in Sweden, where a zero-tolerance law operates. MEASUREMENTS Specimens of blood or urine were subjected to a broad screening analysis by enzyme immunoassay methods. THC positives were verified by analysis of blood by gas chromatography-mass spectrometry (GC-MS) with a deuterium-labelled internal standard (d(3)-THC). All toxicology results were entered into a database (TOXBASE) along with the age and gender of apprehended drivers. FINDINGS Over a 10-year period (1995-2004), between 18% and 30% of all DUID suspects had measurable amounts of THC in their blood (> 0.3 ng/ml) either alone or together with other drugs. The mean age [+/- standard deviation (SD)] of cannabis users was 33 +/- 9.4 years (range 15-66 years), with a strong predominance of men (94%, P < 0.001). The frequency distribution of THC concentrations (n = 8794) was skewed markedly to the right with mean, median and highest values of 2.1 ng/ml, 1.0 ng/ml and 67 ng/ml, respectively. The THC concentration was less than 1.0 ng/ml in 43% of cases and below 2.0 ng/ml in 61% of cases. The age of offenders was not correlated with the concentration of THC in blood (r = -0.027, P > 0.05). THC concentrations in blood were higher when this was the only psychoactive substance present (n = 1276); mean 3.6 ng/ml, median 2.0 ng/ml compared with multi-drug users; mean 1.8 ng/ml, median 1.0 ng/ml (P < 0.001). In cases with THC as the only drug present the concentration was less than 1.0 ng/ml in 26% and below 2.0 ng/ml in 41% of cases. The high prevalence of men, the average age and the concentrations of THC in blood were similar in users of illicit drugs (non-traffic cases). CONCLUSIONS The concentration of THC in blood at the time of driving is probably a great deal higher than at the time of sampling (30-90 minutes later). The notion of enacting science-based concentration limits of THC in blood (e.g. 3-5 ng/ml), as discussed in some quarters, would result in many individuals evading prosecution. Zero-tolerance or limit of quantitation laws are a much more pragmatic way to enforce DUID legislation.

Disappearance rate of ethanol from the blood of human subjects: implications in forensic toxicology

This article outlines major developments in knowledge about the human metabolism of ethanol. The results of a large number of controlled experiments aimed at measuring the rate of ethanol elimination from the blood are reported. The factors that influence the rate of ethanol elimination from blood, such as the amount of ethanol ingested, the drinking habits of the subjects, and the effect of food taken together with, or before, drinking were investigated. The slowest rate of ethanol disappearance was observed in a healthy male subject who ingested 0.68 g ethanol/kg body weight after an overnight (8 h) fast; the beta-slope was 9 mg/dL/h. The fastest rate of ethanol disappearance was observed in a male chronic alcoholic during detoxification; the beta-slope was 36 mg/dL/h. This four-fold difference in the rate of ethanol disposal should be considered when the pharmacokinetics of ethanol become an issue in drinking and driving trials, for example, when retrograde estimations are attempted.

Driving under the influence of drugs in Sweden with zero concentration limits in blood for controlled substances

Objective. This article describes the background and implementation in Sweden of zero-concentration limits for controlled drugs in the blood of drivers. Eliminating the need to prove that a persons ability to drive safely was impaired by drugs has greatly simplified the prosecution case, which now rests primarily on the forensic toxicology report. Driving under the influence of a prescription drug listed as a controlled substance is exempt from the zero-limit law provided the medication was being used in accordance with a physicians direction and the person was not considered unfit to drive. Methods. The prevalence of driving under the influence of drugs (DUID) in Sweden was evaluated from police reports with the main focus on the toxicological findings. A large case series of DUID suspects was compared before and after introducing zero concentration limits in blood for controlled substances on July 1, 1999. The spectrum of drugs used by typical offenders and the concentrations of various licit and illicit substances in blood were evaluated and compared. Results. Immediately after the zero-limit law came into force, the number of cases of DUID submitted by the police for toxicological analysis increased sharply and is currently ten-fold higher than before the new legislation. Statistics show that about 85% of all blood samples sent for toxicological analysis have one or more banned substances present. Amphetamine is by far the leading drug of abuse in Sweden and was identified in about 50–60% of all DUID suspects either alone or together with other controlled substances. The next most frequently encountered illicit drug was tetrahydrocannabinol (THC), with positive findings in about 20–25% of cases. Various prescription drugs, mainly sedative-hypnotics like diazepam and flunitrazepam, were also highly prevalent and these occurred mostly together with illicit substances. Opiates, such as 6-acetyl morphine and morphine, the metabolites of heroin, were high on the list of substances identified. Most DUID suspects in Sweden were men (85%) who were poly-drug users combining illicit substances, like amphetamine and/or cannabis, with a prescription medication such as various benzodiazepines. Conclusions. Swedens zero-concentration limit has done nothing to reduce DUID or deter the typical offender because recidivism is high in this population of individuals (40–50%). Indeed, many traffic delinquents in Sweden are criminal elements in society with previous convictions for drunk and/or drugged driving as well as other offenses. The spectrum of drugs identified in blood samples from DUID suspects has not changed much since the zero-limit law was introduced.

Impact factors of forensic science and toxicology journals: what do the numbers really mean?

This article presents review and opinion about the use and abuse of journal impact factors for judging the importance and prestige of scientific journals in the field of forensic science and toxicology. The application of impact factors for evaluating the published work of individual scientists is also discussed. The impact factor of a particular journal is calculated by dividing the number of current year citations to a journals articles that were published in the previous 2 years by the total number of citable items (articles and reviews) published in the same 2-year period. Journal impact factors differ from discipline to discipline and range from 0 for a journal whose articles are not cited in the previous 2 years to 46 for a journal where the average recent article is cited 46 times per year. The impact factor reflects the citation rate of the average article in a journal and not a specific article. Many parameters influence the citation rate of a particular journals articles and, therefore, its impact factor. These include the visibility and size of the circulation of the journal including availability of electronic formats and options for on-line search and retrieval. Other things to consider are editorial standards especially rapid and effective peer-reviewing and a short time lag between acceptance and appearance in print. The number of self-citations and citation density (the ratio of references to articles) and also the inclusion of many review articles containing hundreds of references to recently published articles will boost the impact factor. Judging the importance of a scientists work based on the average or median impact factor of the journals used to publish articles is not recommended. Instead an article-by-article citation count should be done, but this involves much more time and effort. Moreover, some weighting factor is necessary to allow for the number of co-authors on each article and the relative positioning of the individual names should also be considered. Authors should submit their research results and manuscripts to journals that are easily available and are read by their peers (the most interested audience) and pay less attention to journal impact factors. To assess the true usefulness of a persons contributions to forensic science and toxicology one needs to look beyond impact factor and citation counts. For example, one might consider whether the articles contained new ideas or innovations that proved useful in routine forensic casework or are widely relied upon in courts of law as proof source.

CONCENTRATION-TIME PROFILES OF ETHANOL IN ARTERIAL AND VENOUS BLOOD AND END-EXPIRED BREATH DURING AND AFTER INTRAVENOUS INFUSION

Ethanol (0.40 g/kg) was administered to 13 healthy men by intravenous (i.v.) infusion at a constant rate for 30 min. The concentrations of ethanol in arterial blood (ABAC), venous blood (VBAC), and end-expired breath (BrAC) were measured at 17 exactly timed intervals. Blood-ethanol was determined by headspace gas chromatography and breath-ethanol was measured with a quantitative infrared analyzer (DataMaster). BrAC was multiplied by 2300 to estimate the concentrations of alcohol in blood. During the infusion of ethanol, ABAC exceeded VBAC by about 10 mg/dL on the average and ABAC was also higher than BrAC x 2300 by about 4 mg/dL on average. When infusion of alcohol ended, ABAC, VBAC, and BrAC were 94.8 +/- 2.06 (+/- SE), 84.7 +/- 1.54, and 89.3 +/- 2.10 mg/dL, respectively. The concentrations of alcohol in blood (ABAC and VBAC) and breath decreased abruptly after the administration of alcohol stopped and by 5 min postinfusion, the A-V differences in concentration of ethanol were small or negligible. The mean apparent half-life of the distribution plunge was 7 to 8 min, being about the same for ABAC, VBAC, and BrAC. The disappearance rate of ethanol was 15.5 +/- 0.55 mg/ dL/h (mean +/- SE) for arterial blood, 15.2 +/- 0.49 mg/dL/h for venous blood, and 16.3 +/- 0.73 mg/230 L/h for breath; no significant differences were noted (p > 0.05). We conclude that A-V differences in the concentration of ethanol exist during the loading phase but are rapidly abolished when the administration of ethanol terminates. In the post-absorptive phase of ethanol kinetics, when alcohol has mixed with the total body water, VBAC exceeds ABAC by about 1-2 mg/100 mL on average.