Accuracy and replicability of identifying eyelid tremor as an indicator of recent cannabis smoking.

INTRODUCTION: Cannabis intoxication may increase the risk of motor vehicle crashes. However, reliable methods of assessing cannabis intoxication are limited. The presence of eyelid tremors is among the signs of cannabis use identified under the Drug Evaluation and Classification Program of the International Association of Chiefs of Police. Our objectives were to assess the accuracy and replicability of identifying eyelid tremor as an indicator of recent cannabis smoking using a blinded, controlled study design. METHODS: Adult subjects (N = 103) were recruited into three groups based on their cannabis use history: daily, occasional, and no current cannabis use. Participants' closed eyelids were video recorded for 30 seconds by infrared videography goggles before and at a mean ± standard deviation time of 71.4 ± 4.6 minutes after the onset of a 15-minute interval of ad libitum cannabis flower smoking or vaping. Three observers with expertise in neuro-ophthalmology and medical toxicology were trained on exemplar videos of eyelids to reach a consensus on how to grade eyelid tremor. Without knowledge of subjects' cannabis use history or time point (pre- or post-smoking), observers reviewed each video for eyelid tremor graded as absent, slight, moderate, or severe. During subsequent data analysis, this score was further dichotomized as a consensus score of absent (absent/slight) or present (moderate/severe). RESULTS: Kappa and intraclass correlation coefficient statistics demonstrated moderate agreement among the coders, which ranged from 0.44-0.45 and 0.58-0.61, respectively. There was no significant association between recent cannabis use and the observers' consensus assessment that eyelid tremor was present, and cannabis users were less likely to have tremors (odds ratio: 0.75; 95 percent confidence interval: 0.25, 2.40). The assessment of eyelid tremor as an indicator of recent cannabis smoking had a sensitivity of 0.86, specificity of 0.18, and accuracy of 0.64. DISCUSSION: Eyelid tremor has fair sensitivity but poor specificity and accuracy for identification of recent cannabis use. Inter-rater reliability for assessment of eyelid tremor was moderate for the presence and degree of tremor. The weak association between recent cannabis use and eyelid tremor does not support its utility in identifying recent cannabis use. LIMITATIONS: Videos were recorded at only one time point after cannabis use. Adherence to abstinence could not be strictly supervised. Due to regulatory restrictions, we were unable to control the cannabis product used or administer a fixed Δ9-tetrahydrocannabinol dose. Participants were predominately non-Hispanic and White. CONCLUSIONS: In a cohort of participants with a range of cannabis use histories, acute cannabis smoking was not associated with the presence of eyelid tremor, regardless of cannabis use history, at 70 minutes post-smoking. Additional research is needed to identify the presence of eyelid tremor accurately, determine the relationship between cannabis dose and timeline in relation to last cannabis use to eyelid tremor, and determine how it should be, if at all, utilized for cannabis Drug Recognition Evaluator examinations.

Effects of acute cannabis inhalation on reaction time, decision-making, and memory using a tablet-based application.

BACKGROUND: Acute cannabis use has been demonstrated to slow reaction time and affect decision-making and short-term memory. These effects may have utility in identifying impairment associated with recent use. However, these effects have not been widely investigated among individuals with a pattern of daily use, who may have acquired tolerance. The purpose of this study was to examine the impact of tolerance to cannabis on the acute effects as measured by reaction time, decision-making (gap acceptance), and short-term memory. METHODS: Participants (ages 25-45) completed a tablet-based (iPad) test battery before and approximately 60 min after smoking cannabis flower. The change in performance from before to after cannabis use was compared across three groups of cannabis users: (1) occasional use (n = 23); (2) daily use (n = 31); or (3) no current use (n = 32). Participants in the occasional and daily use group self-administered ad libitum, by smoking or vaping, self-supplied cannabis flower with a high concentration of total THC (15-30%). RESULTS: The occasional use group exhibited decrements in reaction time (slowed) and short-term memory (replicated fewer shapes) from before to after cannabis use, as compared to the no-use group. In the gap acceptance task, daily use participants took more time to complete the task post-smoking cannabis as compared to those with no use or occasional use; however, the level of accuracy did not significantly change. CONCLUSIONS: The findings are consistent with acquired tolerance to certain acute psychomotor effects with daily cannabis use. The finding from the gap acceptance task which showed a decline in speed but not accuracy may indicate a prioritization of accuracy over response time. Cognitive and psychomotor assessments may have utility for identifying impairment associated with recent cannabis use.

A Latent Variable Analysis of Psychomotor and Neurocognitive Performance After Acute Cannabis Smoking.

Objective: This paper evaluated a novel, tablet-based neurocognitive and psychomotor test battery for detecting impairment from acute cannabis smoking using advanced quantitative methods. The study was conducted in a state with legal, recreational cannabis use and included participants who use cannabis occasionally or daily, and a no use comparison group. Methods: Participants completed a tablet-based test assessing reaction time, decision making, working memory and spatial-motor performance. The test was completed before and after participants smoked cannabis (or after a rest period in the case of controls). An Exploratory Factor Analysis approach was implemented to reduce dimensionality and evaluate correlations across the four assessed domains. Linear regression models were utilized to quantify associations between factor scores and cannabis use groups (daily vs. occasional vs. no use). Results: Seven factors were identified explaining 56.7% of the variance among the 18 measures. Regression models of the change in factors after cannabis smoking indicated those who use cannabis daily demonstrated poorer performance on a latent factor termed Displaced and Delayed (standardized coefficient 0.567, 95% CI: 0.178, 0.955; P = 0.005) compared to those with no use. Those who use cannabis occasionally exhibited a decline in performance on a latent factor termed Recall and Reaction (standardized coefficient 0.714, 95% CI: 0.092, 1.336; P = 0.025) compared to no use. Conclusions: This analysis demonstrates an innovative, quantitative approach to study how cannabis consumption affects neurocognitive and psychomotor performance. Results demonstrated that acute cannabis use is associated with changes in neurocognitive and psychomotor performance, with differences based on the pattern of occasional or daily use.

Blood cannabinoid molar metabolite ratios are superior to blood THC as an indicator of recent cannabis smoking.

INTRODUCTION: Cannabis use is a growing concern in transportation and workplace incidents. Because Δ9-tetrahydrocannabinol is detectable after acute psychoactive effects have resolved, it has limitations as an indicator of recent usage or potential impairment. METHODS: In an observational study of driving and psychomotor performance, we measured whole blood Δ9-tetrahydrocannabinol plus its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol by liquid chromatography with tandem mass spectrometry at baseline and 30 min after starting a 15-minute interval of smoking cannabis in 24 occasional and 32 daily cannabis smokers. We calculated two blood cannabinoid molar metabolite ratios: 1) [Δ9-tetrahydrocannabinol] to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol] and 2) ([Δ9-tetrahydrocannabinol] + [11-hydroxy-Δ9-tetrahydrocannabinol]) to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol]. We compared these to blood [Δ9-tetrahydrocannabinol] alone as indicators of recent cannabis smoking. RESULTS: Median Δ9-tetrahydrocannabinol concentrations increased from 0 ( 0.38). By comparison, a cut-point for Δ9-tetrahydrocannabinol of 5.3 µg/L yielded 88% specificity, 73% sensitivity, and 80% accuracy. CONCLUSIONS: In occasional and daily users, the blood cannabinoid molar metabolite ratios were superior to whole blood Δ9-tetrahydrocannabinol as indicators of recent cannabis smoking. We recommend measurement and reporting of Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol, and their molar metabolite ratios in forensic and safety investigations.

The minor cannabinoid cannabigerol (CBG) is a highly specific blood biomarker of recent cannabis smoking.

INTRODUCTION: The determination of recent cannabis use is of forensic interest in the investigation of automotive crashes, workplace incidents and other mishaps. Because Δ9-tetrahydrocannabinol may persist in blood after psychoactive effects of intoxication resolve, particularly in regular users, short-lived minor cannabinoids such as cannabigerol have merited examination as adjunct indicators of recent cannabis inhalation. METHODS: As part of an observational cohort study, whole blood cannabinoids including cannabigerol were measured in whole blood by liquid chromatography with tandem mass spectrometry at baseline, and 30 minutes after initiation of a 15-minute supervised interval of ad libitum cannabis smoking in occasional (1-2 days/week over the past 30 days) (n = 24) and daily cannabis smokers (n = 32). Per protocol, subjects self-reported abstention from inhaling cannabis (>8 h) or ingesting cannabis (>12 h) prior to baseline measurement. RESULTS: At baseline, none of the occasional users had detectable cannabigerol (limit of detection = 0.2 µg/L), whereas cannabigerol was detectable post-smoking in 7 of 24 (29%). Among daily cannabis users, 2 of 32 (6%) had detectable cannabigerol at baseline, increasing to 21 of 32 (66%) post-smoking. The odds ratio for recent cannabis smoking associated with a detectable cannabigerol was 27 (95% confidence interval: 6.6, 110.3). In this mixed cohort of occasional and daily cannabis users, receiver operator characteristic curve analysis indicated that whole blood cannabigerol concentration of ≥ 0.2 µg/L had 96% specificity, 50% sensitivity, and 73% accuracy for identifying a 15-minute interval of ad libitum cannabis smoking initiated 30 minutes earlier. Post smoking blood Δ9-tetrahydrocannabinol (median = 5.6 µg/L in occasional users, 21.3 µg/L in daily users) was significantly correlated with post-smoking cannabigerol (P < 0.0001). CONCLUSION: Whole blood cannabigerol may have forensic utility as a highly specific albeit insensitive biomarker of recent cannabis smoking.

A Video Segmentation Pipeline for Assessing changes in Pupil Response to Light After Cannabis Consumption.

Due to long-standing federal restrictions on cannabis-related research, the implications of cannabis legalization on traffic and occupational safety are understudied. Accordingly, there is a need for objective and validated measures of acute cannabis impairment that may be applied in public safety and occupational settings. Pupillary response to light may offer an avenue for detection that outperforms typical sobriety tests and THC concentrations. We developed a video processing and analysis pipeline that extracts pupil sizes during a light stimulus test administered with goggles utilizing infrared videography. The analysis compared pupil size trajectories in response to a light for those with occasional, daily, and no cannabis use before and after smoking. Pupils were segmented using a combination of image pre-processing techniques and segmentation algorithms which were validated using manually segmented data and found to achieve 99% precision and 94% F-score. Features extracted from the pupil size trajectories captured pupil constriction and rebound dilation and were analyzed using generalized estimating equations. We find that acute cannabis use results in less pupil constriction and slower pupil rebound dilation in the light stimulus test.

Influence of cannabis use history on the impact of acute cannabis smoking on simulated driving performance during a distraction task.

Objective: This research explores the driving performance of people who use cannabis daily or occasionally during distraction tasks performed following acute cannabis use.Methods: Healthy adults aged 25 to 45 years with different cannabis usage histories were recruited to participate in a within-subjects controlled experiment using a car-based driving simulator. Participants were classified as having daily use (n = 31), occasional use (1 or 2 times per week; n = 24), or no-use (n = 30). Participants completed a practice drive followed by four 5-10 minute driving scenarios during the baseline period. Participants then smoked self-procured cannabis flower ad libitum for up to 15 minutes. Thirty minutes later, they completed four additional 5-10 minute scenarios. Scenarios were paired according to difficulty and randomized across the baseline and post-use periods. Each scenario contained between 0 and 3 repetitions of a distraction task where the participant was prompted by an audio message to select an app from a 4 × 5 grid displayed on a mounted tablet, a step that would require briefly looking away from the roadway. Measures of driving performance (lane departures, standard deviation of lateral position) were assessed during the five-second period following the audio trigger and analyzed using generalized linear mixed models.Results: Those with a pattern of occasional use were significantly more likely to experience a lane departure during distraction periods after acute cannabis use relative to baseline (OR = 3.71, p = 0.04, CI = 1.04, 13.17), while those with daily use did not exhibit a similar increase (OR = 1.56, p = 0.43, CI = 0.52, 4.64). Changes in departure risk were significantly greater for the occasional use group compared to no-use (p = 0.02), but not for the daily use group compared to no-use (p = 0.18). However, following acute use, those who use daily exhibited decreases in speed relative to baseline in comparison to the changes observed in the no-use group (p = 0.02), while differences between occasional and no-use did not reach statistical significance (p = 0.052). Differences in standard deviation of lateral position were not statistically significant, likely due to the short duration of tasks.Conclusions: These results find the largest potential safety concerns associated with a pattern of occasional use, who displayed an increase in lane departures after acute cannabis smoking. Those in the daily use group decreased their speed, which may be interpreted as compensation for drug effects. Further research is needed to understand the effects during longer and more complex secondary tasks.

Simulated driving performance among daily and occasional cannabis users.

OBJECTIVE: Daily cannabis users develop tolerance to some drug effects, but the extent to which this diminishes driving impairment is uncertain. This study compared the impact of acute cannabis use on driving performance in occasional and daily cannabis users using a driving simulator. METHODS: We used a within-subjects design to observe driving performance in adults age 25 to 45 years with different cannabis use histories. Eighty-five participants (43 males, 42 females) were included in the final analysis: 24 occasional users (1 to 2 times per week), 31 daily users and 30 non-users. A car-based driving simulator (MiniSim™, National Advanced Driving Simulator) was used to obtain two measures of driving performance, standard deviation of lateral placement (SDLP) and speed relative to posted speed limit, in simulated urban driving scenarios at baseline and 30 min after a 15 min ad libitum cannabis smoking period. Participants smoked self-supplied cannabis flower product (15% to 30% tetrahydrocannabinol (THC). Blood samples were collected before and after smoking (30 min after the start of smoking). Non-users performed the same driving scenarios before and after an equivalent rest interval. Changes in driving performance were analyzed by repeated measures general linear models. RESULTS: Mean whole blood THC cannabinoids concentrations post smoking were use THC = 6.4 ± 5.6 ng/ml, THC-COOH = 10.9 ± 8.79 ng/mL for occasional users and THC = 36.4 ± 37.4 ng/mL, THC-COOH = 98.1 ± 90.6 ng/mL for daily users. On a scale of 0 to 100, the mean post-use score of subjective high was similar in occasional users and daily users (52.4 and 47.2, respectively). In covariate-adjusted analysis, occasional users had a significant increase in SDLP in the straight road segment from pre to post compared to non-users; non-users decreased by a mean of 1.1 cm (25.5 cm to 24.4 cm) while occasional users increased by a mean of 1.9 cm (21.7 cm to 23.6 cm; p = 0.02). Daily users also increased adjusted SDLP in straight road segments from baseline to post-use (23.2 cm to 25.0 cm), but the change relative to non-users was not statistically significant (p = 0.08). The standardized mean difference in unadjusted SDLP from baseline to post-use in the straight road segments comparing occasional users to non-users was 0.64 (95% CI 0.09 - 1.19), a statistically significant moderate increase. When occasional users were contrasted with daily users, the baseline to post changes in SDLP were not statistically significant. Daily users exhibited a mean decrease in baseline to post-use adjusted speed in straight road segments of 1.16 mph; a significant change compared to slight speed increases in the non-users and occasional users (p = 0.02 and p = 0.01, respectively). CONCLUSION: We observed a decrement in driving performance assessed by SDLP after acute cannabis smoking that was statistically significant only in the occasional users in comparison to the nonusers. Direct contrasts between the occasional users and daily users in SDLP were not statistically significant. Daily users drove slower after cannabis use as compared to the occasional use group and non-users. The study results do not conclusively establish that occasional users exhibit more driving impairment than daily users when both smoke cannabis ad libitum.

Sudden Deaths Among Oil and Gas Extraction Workers Resulting from Oxygen Deficiency and Inhalation of Hydrocarbon Gases and Vapors - United States, January 2010-March 2015.

In 2013, an occupational medicine physician from the University of California, San Francisco, contacted CDC's National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA) about two oil and gas extraction worker deaths in the western United States. The suspected cause of these deaths was exposure to hydrocarbon gases and vapors (HGVs) and oxygen (O2)-deficient atmospheres after opening the hatches of hydrocarbon storage tanks. The physician and experts from NIOSH and OSHA reviewed available fatality reports from January 2010 to March 2015, and identified seven additional deaths with similar characteristics (nine total deaths). Recommendations were made to industry and regulators regarding the hazards associated with opening hatches of tanks, and controls to reduce or eliminate the potential for HGV exposure were proposed. Health care professionals who treat or evaluate oil and gas workers need to be aware that workers might report symptoms of exposure to high concentrations of HGVs and possible O2 deficiency; employers and workers need to be aware of this hazard and know how to limit exposure. Medical examiners investigating the death of oil and gas workers who open tank hatches should consider the contribution of O2 deficiency and HGV exposure.

Description of 3,180 courses of chelation with dimercaptosuccinic acid in children ≤ 5 y with severe lead poisoning in Zamfara, Northern Nigeria: a retrospective analysis of programme data.

BACKGROUND: In 2010, Médecins Sans Frontières (MSF) discovered extensive lead poisoning impacting several thousand children in rural northern Nigeria. An estimated 400 fatalities had occurred over 3 mo. The US Centers for Disease Control and Prevention (CDC) confirmed widespread contamination from lead-rich ore being processed for gold, and environmental management was begun. MSF commenced a medical management programme that included treatment with the oral chelating agent 2,3-dimercaptosuccinic acid (DMSA, succimer). Here we describe and evaluate the changes in venous blood lead level (VBLL) associated with DMSA treatment in the largest cohort of children ≤ 5 y of age with severe paediatric lead intoxication reported to date to our knowledge. METHODS AND FINDINGS: In a retrospective analysis of programme data, we describe change in VBLL after DMSA treatment courses in a cohort of 1,156 children ≤ 5 y of age who underwent between one and 15 courses of chelation treatment. Courses of DMSA of 19 or 28 d duration administered to children with VBLL ≥ 45 µg/dl were included. Impact of DMSA was calculated as end-course VBLL as a percentage of pre-course VBLL (ECP). Mixed model regression with nested random effects was used to evaluate the relative associations of covariates with ECP. Of 3,180 treatment courses administered, 36% and 6% of courses commenced with VBLL ≥ 80 µg/dl and ≥ 120 µg/dl, respectively. Overall mean ECP was 74.5% (95% CI 69.7%-79.7%); among 159 inpatient courses, ECP was 47.7% (95% CI 39.7%-57.3%). ECP after 19-d courses (n = 2,262) was lower in older children, first-ever courses, courses with a longer interval since a previous course, courses with more directly observed doses, and courses with higher pre-course VBLLs. Low haemoglobin was associated with higher ECP. Twenty children aged ≤ 5 y who commenced chelation died during the period studied, with lead poisoning a primary factor in six deaths. Monitoring of alanine transaminase (ALT), creatinine, and full blood count revealed moderate ALT elevation in <2.5% of courses. No clinically severe adverse drug effects were observed, and no laboratory findings required discontinuation of treatment. Limitations include that this was a retrospective analysis of clinical data, and unmeasured variables related to environmental exposures could not be accounted for. CONCLUSIONS: Oral DMSA was a pharmacodynamically effective chelating agent for the treatment of severe childhood lead poisoning in a resource-limited setting. Re-exposure to lead, despite efforts to remediate the environment, and non-adherence may have influenced the impact of outpatient treatment. Please see later in the article for the Editors' Summary.

The role of chelation in the treatment of arsenic and mercury poisoning.

Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential antidote the arsenical warfare agent lewisite (dichloro[2-chlorovinyl]arsine). DMPS (unithiol) and DMSA (succimer), dithiol water-soluble analogs of BAL, were developed in the Soviet Union and China in the late 1950s. These three agents have remained the mainstay of chelation treatment of arsenic and mercury intoxication for more than half a century. Animal experiments and in some instances human data indicate that the dithiol chelators enhance arsenic and mercury excretion. Controlled animal experiments support a therapeutic role for these chelators in the prompt treatment of acute poisoning by arsenic and inorganic mercury salts. Treatment should be initiated as rapidly as possible (within minutes to a few hours), as efficacy declines or disappears as the time interval between metal exposure and onset of chelation increases. DMPS and DMSA, which have a higher therapeutic index than BAL and do not redistribute arsenic or mercury to the brain, offer advantages in clinical practice. Although chelation following chronic exposure to inorganic arsenic and inorganic mercury may accelerate metal excretion and diminish metal burden in some organs, potential therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished in cases of chronic metal intoxication.

Fatal cesium chloride toxicity after alternative cancer treatment.

BACKGROUND: Cesium chloride (CsCl) is sold as a treatment for several types of cancers. The purported mechanism of action is alkalinization of relatively acidic neoplastic cells. The efficacy of CsCl has not been demonstrated in controlled experiments. Oral and intravenous CsCl use has been associated with seizures, cardiotoxicity, syncope, and death. Although intratumoral treatment with various antineoplastic agents is described, no cases of intratumoral cancer treatment with CsCl have been found in the medical literature. The case described here appears to be of the first reported patient with CsCl toxicity secondary to subcutaneous exposure after attempted intratumoral injection. CASE DETAILS: A 61-year-old woman presented in cardiac arrest 20 hours after injecting 9 mL of an oral CsCl preparation around a mass in her breast. She had been taking the CsCl orally for approximately 1 year to treat her breast mass. The patient had a headache and nausea for several hours after injection and then experienced ventricular tachycardia arrest at home. She received advanced cardiac life support care and multiple antiarrhythmic medications and underwent electrical cardioversion early in the course of the arrest. After stabilization, her electrocardiogram revealed QT interval prolongation to >700 milliseconds. Upon discovery of her CsCl exposure, she was treated with Prussian blue. Her initial whole blood cesium level was 100,000 µg/L (reference range <10 µg/L). Her QT prolongation resolved after several days, but she experienced no meaningful postarrest neurologic recovery and died at home less than a week after exposure. DISCUSSION: CsCl is sold as an alternative treatment for cancer. There is no demonstrable efficacy, and clear evidence shows life-threatening toxicity. Reported here is a case of fatal CsCl toxicity after attempted intratumoral injection.

Massive human ingestion of orpiment (arsenic trisulfide).

BACKGROUND: Because the toxicity of arsenic is well known, arsenic-containing compounds have frequently been ingested for suicidal purposes. We report a case of attempted suicide by massive ingestion of arsenic trisulfide, an arsenic mineral of low solubility, which resulted in minimal symptoms. CASE REPORT: An asymptomatic 57-year-old man presented to an Emergency Department 13h after his reported ingestion of approximately 84g of arsenic contained in a mineral specimen of orpiment (arsenic trisulfide) that had been crushed and mixed with an alcoholic beverage and food. His only symptom before presentation was nausea. Physical examination was unremarkable, and diagnostic tests included a normal electrolyte panel, a normal serum lactate, and a normal electrocardiogram. An abdominal radiograph revealed hyper-dense material scattered throughout the large intestine. As per the recommendations of the regional poison center, the patient was managed with whole bowel irrigation with a polyethylene glycol solution, maintenance intravenous hydration, and observation on a telemetry unit. Chelation was not performed. A spot urine specimen collected 12h after admission contained 1490µg of total arsenic per liter (background range<50µg per liter). The patient remained asymptomatic throughout his hospital course. Follow-up studies revealed a diminution in both intra-abdominal radiopacities and urine arsenic concentration. X-ray diffraction analysis of the specimen confirmed its identity as arsenic trisulfide. CONCLUSIONS: Our experience demonstrates that massive ingestion of a poorly soluble inorganic arsenic compound can be successfully managed with gastrointestinal decontamination alone without chelation, provided that the patient remains asymptomatic during close clinical monitoring.

National Institute for Occupational Safety and Health Nanomaterials and Worker Health Conference--medical surveillance session summary report.

OBJECTIVES: The goal of these sessions was to identify current practices and recommendations regarding medical surveillance for nanomaterial workers. METHODS: Conference participants met in three discussion groups. RESULTS: There were few existing programs directed to nanomaterial workers. Participants expressed a range of views, from feeling that comprehensive medical surveillance is important currently to suggesting that targeted medical surveillance will become important when more complete data are available to assess risks. CONCLUSIONS: Results of health outcomes research for ultrafine air pollution and toxicological information about specific nanomaterials should inform the design of medical surveillance programs. Groups with high exposures should be identified and targeted. Overall, because of uncertainties in the health effects of concern, investments in control measures, exposure assessment efforts, and exposure registries are currently most likely to be important prevention strategies.

Recommendations for medical management of adult lead exposure.

Research conducted in recent years has increased public health concern about the toxicity of lead at low dose and has supported a reappraisal of the levels of lead exposure that may be safely tolerated in the workplace. In this article, which appears as part of a mini-monograph on adult lead exposure, we summarize a body of published literature that establishes the potential for hypertension, effects on renal function, cognitive dysfunction, and adverse female reproductive outcome in adults with whole-blood lead concentrations < 40 microg/dL. Based on this literature, and our collective experience in evaluating lead-exposed adults, we recommend that individuals be removed from occupational lead exposure if a single blood lead concentration exceeds 30 microg/dL or if two successive blood lead concentrations measured over a 4-week interval are > or = 20 microg/dL. Removal of individuals from lead exposure should be considered to avoid long-term risk to health if exposure control measures over an extended period do not decrease blood lead concentrations to < 10 microg/dL or if selected medical conditions exist that would increase the risk of continued exposure. Recommended medical surveillance for all lead-exposed workers should include quarterly blood lead measurements for individuals with blood lead concentrations between 10 and 19 microg/dL, and semiannual blood lead measurements when sustained blood lead concentrations are < 10 microg/dL. It is advisable for pregnant women to avoid occupational or avocational lead exposure that would result in blood lead concentrations > 5 microg/dL. Chelation may have an adjunctive role in the medical management of highly exposed adults with symptomatic lead intoxication but is not recommended for asymptomatic individuals with low blood lead concentrations.