Alcohol metabolism of local Chinese in Hong Kong: a statistical determination on the effects of various physiological factors

A study was designed to examine the elimination rate of alcohol from the body of the local Chinese after consumption of different types of alcoholic drinks. The breath alcohol of 184 healthy volunteers was determined and converted into blood alcohol levels after they finished drinking. Information on the type and volume of alcoholic drinks consumed, age group, sex, drinking habit, and drinking on empty stomach or with/after meal was recorded for each participant. The results show that the elimination rate of an individual can be explained in terms of physiological variables including sex and drinking habit. The determined elimination rates allow forensic toxicologists to back calculate the blood alcohol concentration (BAC) of the drivers at the time of accident in drunk driving cases. The elimination rates of blood alcohol at 95% prediction intervals for male and female are in the range of 9.5-23.8 mg/100 ml/h and 11.1-37.1 mg/100 ml/h, respectively.     

Excretion of alcohol in urine and diuresis in healthy men in relation to their age, the dose administered and the time after drinking

Healthy male volunteers drank neat whisky in amounts corresponding to 0.51, 0.68, or 0.85 g ethanol/kg body weight in 15-25 min after an overnight (10 h) fast. Urine was collected immediately before drinking and then at 60 min intervals for 7-8 h after intake. The volumes of urine voided were measured and the concentrations of alcohol (UAC) were determined by an enzymatic method. Ethanol-induced diuresis showed large inter-subject variations. The flow of urine was maximum between 60 and 120 min post-drinking when the median rates of production were 117 ml/h (range 55-335), 113 ml/h (range 41-453) and 373 ml/h (range 215-485) for 0.51, 0.68, and 0.85 g ethanol/kg respectively. The output of urine returned to normal (30-60 ml/h) after the peak UAC had passed despite an elevated blood alcohol concentration (BAC). The average amount of alcohol excreted in urine was 0.29 g (S.D. 0.119), 0.44 g (S.D. 0.246), and 1.00 g (S.D. 0.427) after the consumption of 0.51, 0.68 and 0.85 g ethanol/kg respectively. Neither peak diuresis nor the amount of alcohol excreted depended on a subject's age between 20 and 60 years. This work shows that after drinking a moderate dose of alcohol, only 0.7-1.5% of the amount consumed is excreted unchanged in urine. Ethanol-induced diuresis is most pronounced for the first 1-2 h after drinking (rising BAC). The production of urine returns to normal during the post-absorptive state.     

Ethanol distribution ratios between urine and capillary blood in controlled experiments and in apprehended drinking drivers.

Healthy men drank 0.51, 0.68, and 0.85 g of ethanol per kilogram of body weight as neat whisky in the morning after an overnight fast. During 6 to 8 h after the whisky was consumed, nearly simultaneous specimens of fingertip blood and pooled bladder urine were obtained for analysis of ethanol using an enzymatic method. The mean ratios of ethanol concentration [urine alcohol concentration (UAC)/blood alcohol concentration (BAC)] were mostly less than unity during the absorption phase. The UAC exceeded the BAC in the postpeak phase. The mean UAC/BAC ratios varied between 1.4 and 1.7 when the BAC exceeded 0.50 mg/mL. When the BAC decreased below 0.40 mg/mL, the UAC/BAC ratios increased appreciably. The mean UAC/BAC ratios of ethanol were not dependent on the person's age between the ages of 20 and 60 years old, but there were large variations within the age groups. In apprehended drinking drivers (N = 654) with a mean BAC of 1.55 mg/mL, the UAC/BAC ratio of ethanol varied widely, with a mean value of 1.49. In 12 subjects (3.2%), the ratio was less than or equal to unity. In a second specimen of urine obtained approximately 60 min after an initial void (N = 135), the mean UAC/BAC ratio was 1.35 (standard deviation = 0.17). The magnitude of the UAC/BAC ratio of ethanol can help to establish whether the BAC curve was rising or falling at or near the time of voiding. The status of alcohol absorption needs to be documented if drinking drivers claim ingestion of alcohol after the offence or when back-estimation of the BAC from the time of sampling to the time of driving is required by statute.     

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.     

Peak blood-ethanol concentration and the time of its occurrence after rapid drinking on an empty stomach

Healthy men, 20 to 60 years old, drank a moderate dose of ethanol in the morning after an overnight fast. They consumed either neat whisky in amounts corresponding to 0.34, 0.51, 0.68, 0.85, or 1.02 g of ethanol per kilogram of body weight or 0.80 g/kg ethanol solvent diluted with orange juice. The peak blood-ethanol concentration (BEC) increased with the dose administered, but the time required to reach the peak was not markedly influenced over the range of doses studied. At a dose of 0.68 g/kg, the peak BEC ranged from 52 to 136 mg/dL (N = 83), and slow absorption (a late-occurring peak) produced a lower peak BEC. The peak BEC was reached between 0 and 45 min for 77% of the subjects (N = 152) and between 0 and 75 min for 97% of them. The time of peaking in venous blood occurred, on average, 10 min later than in capillary (fingertip) blood although the peak BEC was not appreciably different; the mean venous BEC was 97.0 mg/dL (range, 76 to 112 mg/dL), and the mean capillary BEC was 99.6 mg/dL (range, 75 to 123 mg/dL). When subjects drank 0.80 g/kg ethanol diluted with orange juice over 30 min, the average BEC increment between the end of drinking and the peak was 33 mg/dL (range, 0 to 58 mg/dL). The rate of absorption of ethanol was 1.78 mg/dL/min (range, 0.52 to 4.8 mg/dL/min), and the peak BEC occurred within 60 min after the end of drinking in 92% of the trials. The largest BEC increment (mean, 21 mg/dL; range, 0 to 44 mg/dL) was seen during the first 15 min after the drinking period.     

涉嫌酒后驾驶交通事故人体损伤与驾驶员血中乙醇质量浓度关系研究

目的探讨涉嫌酒后驾驶所致道路交通事故中人体损伤情况与驾驶员血中乙醇质量浓度关系,为预防、控制道路交通事故及人体损伤提供依据。方法对467例涉嫌酒后驾驶机动车的道路交通事故损伤人员相关鉴定资料与肇事驾驶员血中乙醇质量浓度进行系统分析性研究。结果涉嫌酒后驾驶发生道路交通事故的损伤人员中,以20~39岁男性居多;事故中驾驶员损伤机率最高;酒后交通事故以长头小车及摩托车最多,而驾驶员血中乙醇质量浓度（BAC）为0.1~20mg/100mL浓度的摩托车驾乘人员伤亡构成比最高;酒后驾驶机动车肇事导致的人体致命性损伤及人员死亡的饮酒组危险程度均高于未饮酒组,在驾驶员血中乙醇质量浓度（BAC）为0.1~20mg/100mL组与20.1~80mg/100mL组比较无明显差异。结论酒后驾驶肇事导致的人员伤亡比未饮酒驾车交通事故严重;未达酒后驾车组（BAC为0.1~20mg/100mL）和酒后驾车组（BAC为20.1~80mg/100mL）交通事故导致的人员伤亡无明显差异。研究结果提示,应降低饮酒后驾车血中乙醇质量浓度（BAC）法定标准阈值,进一步控制和减少道路交通事故人身伤亡率。     

Disappearance rate of alcohol from the blood of drunk drivers calculated from two consecutive samples; what do the results really mean?

Based on a large material (N = 2354) of double blood specimens from drunk drivers apprehended in The Netherlands, we selected 1314 cases for further evaluation. The difference BAC2-BAC1 was used as index of alcohol elimination rate from the blood. The results ranged from below 0.10 to 0.64 mg/ml/h, with a mean of 0.22 mg/ml/h. At least about 2% of drivers were still absorbing alcohol as indicated by a rising BAC. Some likely mechanisms are discussed that might account for the wide range of alcohol elimination rates observed.     

A fatal case of pure ethanol ingestion

An adult male was found dead in a car with two empty bottles (500 ml x 2) labeled dehydrated ethanol (>99.5%, v/v). At autopsy, extensive pancreatic necrosis with severe hemorrhage was observed. High concentrations of ethanol were detected in blood (8.14 mg/ml), urine (8.12 mg/ml) and tissue specimens. The cause of death was determined to be an acute alcohol intoxication caused by ingesting approximately 1l dehydrated ethanol.     

论道路交通事故与驾驶员血中酒精含量关系

目的探讨道路交通事故与饮酒驾车血中酒精含量关系及其法医学意义,为预防、控制道路交通事故提供重要依据。方法对2005份道路交通事故肇事驾驶员血酒精鉴定资料进行系统分析性研究。结果饮酒驾车以男性为主,女性饮酒驾车出现醉酒驾车的比例与男性无差别。市区驾驶员醉酒驾车高于郊区。驾驶员BAC<20mg/100mL肇事导致死亡的比例高于饮酒驾车肇事组(BAC20￣79mg/100ML),而BAC≥80mg/100mL则低于饮酒驾车肇事组。结论应降低饮酒驾车和醉酒驾车BAC标准,以利于减少交通事故肇事死亡率。     

Reliability of breath-alcohol analysis in individuals with gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is widespread in the population among all age groups and in both sexes. The reliability of breath alcohol analysis in subjects suffering from GERD is unknown. We investigated the relationship between breath-alcohol concentration (BrAC) and blood-alcohol concentration (BAC) in 5 male and 5 female subjects all suffering from severe gastroesophageal reflux disease and scheduled for antireflux surgery. Each subject served in two experiments in random order about 1-2 weeks apart. Both times they drank the same dose of ethanol (approximately 0.3 g/kg) as either beer, white wine, or vodka mixed with orange juice before venous blood and end-expired breath samples were obtained at 5-10 min intervals for 4 h. An attempt was made to provoke gastroesophageal reflux in one of the drinking experiments by applying an abdominal compression belt. Blood-ethanol concentration was determined by headspace gas chromatography and breath-ethanol was measured with an electrochemical instrument (Alcolmeter SD-400) or a quantitative infrared analyzer (Data-Master). During the absorption of alcohol, which occurred during the first 90 min after the start of drinking, BrAC (mg/210 L) tended to be the same or higher than venous BAC (mg/dL). In the post-peak phase, the BAC always exceeded BrAC. Four of the 10 subjects definitely experienced gastric reflux during the study although this did not result in widely deviant BrAC readings compared with BAC when sampling occurred at 5-min intervals. We conclude that the risk of alcohol erupting from the stomach into the mouth owing to gastric reflux and falsely increasing the result of an evidential breath-alcohol test is highly improbable.     

The influence of sex hormones on the elimination kinetics of ethanol

The goal of the investigation was to research the influence of sex hormones on the elimination kinetics of ethanol. Forty-seven healthy men (average age 25+/-6.1 years) and 61 healthy women (average age 24+/-2.4 years) received 0.79-0.95g of ethanol/kg body weight in the form of an alcohol beverage of their choice. The target concentration for both sexes was a blood alcohol concentration (BAC) of 1.10g/kg. Blood samples for the determination of the ethanol concentration followed in the elimination phase in 10-20min intervals. The sex hormone levels (estradiol, progesterone and testosterone) were determined concomitantly from the serum. In men, the mean testosterone concentration was 5.3+/-1.6ng/ml, the mean estradiol concentration was 34.6+/-13.6pg/ml and the mean progesterone concentration was 0.9+/-0.3ng/ml. In women, the mean estradiol concentration was 47.6+/-52.6pg/ml and the mean testosterone concentration was 0.8+/-0.4ng/ml. Progesterone displayed a so-called dummy effect in women. In the high progesterone group (n=11), the mean concentration was 11.1+/-3.5ng/ml and in the low progesterone group (n=50) the mean was 0.6+/-0.3ng/ml. The mean hourly elimination rate (beta60) was 0.1677+/-0.0311g/kg/h in men. In women, the mean hourly elimination rate was 0.2044+/-0.0414g/kg/h in the high progesterone group and 0.1850+/-0.0276g/kg/h in the low progesterone group (p<0.05). The beta60 for women in the low progesterone group was significantly higher than that of the men, whose progesterone levels fell within a similar range (p>0.01). These results allow one to conclude that the gender differences in the pharmacokinetics of ethanol can partly, but not completely, be explained by progesterone levels.     

A pharmacokinetic study of ethyl glucuronide in blood and urine: applications to forensic toxicology

This pharmacokinetic study investigated the kinetics of ethanol and its metabolite ethyl glucuronide (EtG) in blood and urine during the whole time course of absorption and elimination. There are few previous studies on the kinetics of EtG in blood, and we wanted to evaluate whether such knowledge could yield valuable information regarding the time of ethanol ingestion in forensic cases, such as, for instance, drunk driving. Ten male volunteers consumed ethanol at a fixed dose of 0.5 g/kg body weight in a fasted state. Blood samples were collected for 14 h and urine samples were collected for 45-50 h after the start of drinking. EtG reached its maximum concentration (C(max)) in blood after a median of 4 h (range 3.5-5), a median of 3 h (range 2-4.5) after C(max) for ethanol. The ethanol-to-EtG ratios in blood (ethanol in g/L, EtG in mg/L) were >1 only for the first median 3.5 h (range 2.5-3.5) after drinking. EtG elimination occurred with a median half-life of 2.2 h (range 1.7-3.1 h), and the renal clearance was 8.32 L/h (median, range 5.25-20.86). The concentrations of EtG were always much higher in urine than in blood. The total amount of EtG excreted in the urine was median 30 mg (range 21.5-39.7), representing 0.017% (median, range 0.013-0.022) of the ethanol given, on a molar basis. The information from the present study may be a valuable supplement to determine the time of ethanol ingestion. For this purpose, two subsequent increasing EtG values and a high ethanol-to-EtG ratio in blood would support information of recent drinking.     

Ethyl glucuronide concentrations in two successive urinary voids from drinking drivers: relationship to creatinine content and blood and urine ethanol concentrations

The concentrations of alcohol in blood (BAC) and two successive urine voids (UAC) from 100 drunk drivers were compared with the concentration of ethyl glucuronide (EtG), a minor metabolite of ethanol in urine, and the urinary creatinine content as an indicator of dilution. The subjects consisted of 87 men with mean age 42.2+/-14.2 years (+/-standard deviation, S.D.) and 13 women with mean age 42.5+/-14.4 years. Ethanol was measured in blood and urine by headspace gas chromatography (GC) and EtG was determined in urine by liquid chromatography-mass spectrometry (LC-MS). The mean UAC was 2.53+/-1.15g/l for first void compared with 2.35+/-1.17g/l for second void, decreasing by 0.18+/-0.24g/l on average (P<0.001 in paired t-test). The ratios of UAC/BAC were 1.35+/-0.25 for first void and 1.20+/-0.16 for second void and the difference of 0.15+/-0.27 was statistically significant (P<0.001). The UAC/BAC ratio was not correlated with creatinine content of the urine specimens, whereas the concentration of urinary EtG was positively correlated with creatinine (r=0.64 for first void and r=0.62 for second void). The UAC was not correlated with urinary EtG directly (r=-0.03 for first void and r=0.08 for second void) but after adjusting for the relative dilution of the specimens (EtG/creatinine ratio) statistically significant positive correlations were obtained (r=0.58 for first void and r=0.57 for second void). The dilution of the urine, as reflected in creatinine content, is important to consider when EtG measurements are interpreted. The excretion of EtG in urine, like glucuronide conjugates of other drugs, is influenced by diuresis. EtG represents a sensitive and specific marker of acute alcohol ingestion with applications in clinical and forensic medicine.     

Widmark factors for local Chinese in Hong Kong. A statistical determination on the effects of various physiological factors

The Widmark formula has been widely adopted in forensic applications to drink driving cases for the last 70 years. It is known that the amount of alcohol consumed and the body weight of the drinkers are important information for the estimation of blood alcohol concentration (BAC). However, the direct application of the Widmark factors derived from Caucasian to the calculation of BAC for the Chinese population often encounters serious challenges. Owing to this inherent weakness, a thorough analysis to determine the theoretical Widmark factors for the Chinese population, r(0) at the start of drinking and the practical factors, r(peak), at peak BAC was conducted. In the present study, other factors such as gender, stomach condition and other physiological conditions are taken into account. The determined theoretical Widmark factors, r(0,) for local Chinese male and female are 0.68 and 0.59 (with BAC in the units of weight/volume), respectively, demonstrating the applicability of the Widmark formula to the Chinese population. The practical factors at peak BAC, r(peak), were also determined to serve the forensic purpose of refuting the "hip-flask" defence in drink driving cases. Findings show that gender and stomach condition are the key factors that could statistically explain the variability of both r(0) and r(peak).     

Fatal overdose of the herbicide bentazone

A 59-year-old woman who intentionally ingested 100-200 ml Basagran was taken to the hospital with a cardiac arrest 2 days after she had consumed the herbicide. During this period she suffered vomiting, urination and diarrhoea and she was drowsy with a muddled speech. Biological samples obtained at the autopsy were analysed and presence of bentazone, alcohol and an active metabolite of citalopram were detected. Blood concentrations of bentazone, alcohol and desmethyl-citalopram were 625 mg/kg, 0.62 g/l and 0.03 mg/kg, respectively.     

Consumption of a large dose of alcohol in a short time span.

Blood alcohol concentrations (BAC) and time to peak BAC were determined in 16 subjects after ingestion of a large quantity of alcoholic beverages within a short drinking time span not exceeding 30 min. The first group (7 subjects) consumed alcohol after a 3- to 4-h fast. In the second group (9 subjects) the consumption of alcohol took place after eating a large meal. Venous blood samples taken 30 min after drinking finished were compared to the near-simultaneous Breathalyzer results. In addition, the minimum duration of a BAC plateau for these drinking circumstances was assessed.     

Alcohol content of beer and malt beverages: forensic consideration

Beer consumption is commonly an issue in a medico-legal setting, requiring estimates either of a likely blood alcohol concentration (BAC) for a given pattern of consumption or vice versa. Four hundred and four beers and malt beverages available for sale in the State of Washington were tested by gas chromatography for their alcohol content. Considerable variability in the alcoholic strength was found, even within the same class. Overall the range of concentrations was 2.92%v/v to 15.66%v/v. The mean alcohol concentration for ales was 5.51%v/v (SD 1.23%v/v), and for lagers, 5.32% (SD 1.43%v/v). Some specialty brews had characteristically higher or lower mean concentrations: ice beers 6.07%v/v, malt liquor 7.23%v/v, light beer 4.13%v/v, seasonal ales 6.30%v/v. Six brands of lager and four light beers account for the majority of all beer sales in the United States, and the mean alcohol concentration for these products was measured as 4.73%v/v and 4.10%v/v respectively. Few of the beers (17%) were labeled with respect to alcohol content, and in some cases, there was a significant disparity between the concentration listed on the label, and the measured alcohol concentration. Toxicologists need to exercise caution when performing Widmark type calculations, using all available information to select the most appropriate estimate for alcoholic strength of a beer or malt beverage.     

A fatal poisoning caused by methomyl and nicotine

A 35-year-old male was found lying in a prone position in his room. He was in cardiopulmonary arrest on arrival to hospital and was pronounced dead. There was no attempt at resuscitation. No miosis was observed on admission. At post-mortem his stomach contained 170 g greenish liquid with a small amount of shredded tobacco leaves. The serum cholinesterase activities were 47-90 IU (normal range for male: 200-440 IU). GC and GC-MS analyses showed nicotine (21.8 mg), methomyl (304 mg), and triazolam (1.69 mg) in his stomach. He had consumed tobacco leaves, Lannate containing water soluble methomyl (45%), and Halcion tablets containing 0.25 mg triazolam. Methomyl concentrations in blood were 3-8 ng/ml. Substantial amounts of methomyl (2260-2680 ng/ml) were detected in cerebrospinal fluid and vitreous humor. Nicotine concentrations in blood ranged from 222 to 733 ng/ml. A small amount of triazolam was detected only in bile (176 ng/ml) and liver (23 ng/g). The cause of death was respiratory paralysis produced by the additive effects of methomyl and nicotine shortly after consumption.     

Determination of ethylene glycol tissue content after fatal oral poisoning and pathologic findings

A 23-year-old comatose man who had drunk an unknown amount of ethylene glycol was admitted to the hospital 5 hours after ingestion. The initial plasma ethylene glycol concentration was 116.2 mg/100 ml. A severe metabolic acidosis was present. Despite aggressive therapy with ethanol, hemodialysis, and intensive care support, the patient died 27 hours after poisoning. The plasma ethylene glycol concentration immediately before death was 35.9 mg/100 ml. Brain edema and acute renal tubular necrosis were evident at postmortem examination. Oxalate crystals were identified in both organs. Ethylene glycol content or concentration was determined in tissues and biologic fluids.     

Computer-aided headspace gas chromatography applied to blood-alcohol analysis: importance of online process control

This paper describes the analysis of ethanol in blood specimens from suspect drunk drivers and the associated quality assurance procedures currently used in Sweden for legal purposes. Aliquots of whole blood from two separate Vacutainer tubes are diluted with 1-propanol as internal standard before analysis by headspace gas chromatography (HS-GC) with three different stationary phases: Carbopak B, Carbopak C, and 15% Carbowax 20 M. The actual HS-GC analysis, the integration of chromatographic peaks, the collection and processing of results, as well as the quality control tests involve the use of computer-aided techniques. The standard deviation of analysis(y) increased with concentration of ethanol in the blood specimen(x), and above 0.50 mg/g the regression equation was y = 0.0033 + 0.0153x. The prosecution blood-alcohol concentration (BAC) is the mean of three separate determinations made by different laboratory technicians working independently with different sets of equipment. A deduction is made from the mean analytical result to compensate for random and systematic errors inherent in the method. At BACs of 0.5 and 1.5 mg/g, which are the statutory limits in Sweden, the allowances currently made are 0.06 and 0.09 mg/g, respectively. Accordingly, the reduced prosecution BAC is less than the actual BAC with a statistical confidence of 99.9%.