Secondary indoor air pollution and passive smoking associated with cannabis smoking using electric cigarette device-demonstrative in silico study.

With electronic (e)-liquids containing cannabis components easily available, many anecdotal examples of cannabis vaping using electronic cigarette devices have been reported. For electronic cigarette cannabis vaping, there are potential risks of secondary indoor air pollution from vapers. However, quantitative and accurate prediction of the inhalation and dermal exposure of a passive smoker in the same room is difficult to achieve due to the ethical constraints on subject experiments. The numerical method, i.e., in silico method, is a powerful tool to complement these experiments with real humans. In this study, we adopted a computer-simulated person that has been validated from multiple perspectives for prediction accuracy. We then conducted an in silico study to elucidate secondary indoor air pollution and passive smoking associated with cannabis vaping using an electronic cigarette device in an indoor environment. The aerosols exhaled by a cannabis vaper were confirmed to be a secondary emission source in an indoor environment; non-smokers were exposed to these aerosols via respiratory and dermal pathways. Tetrahydrocannabinol was used as a model chemical compound for the exposure study. Its uptake by the non-smoker through inhalation and dermal exposure under a worst-case scenario was estimated to be 5.9% and 2.6% of the exhaled quantity from an e-cigarette cannabis user, respectively.

Measurement of heating coil temperature for e-cigarettes with a "top-coil" clearomizer.

OBJECTIVES: To determine the effect of applied power settings, coil wetness conditions, and e-liquid compositions on the coil heating temperature for e-cigarettes with a "top-coil" clearomizer, and to make associations of coil conditions with emission of toxic carbonyl compounds by combining results herein with the literature. METHODS: The coil temperature of a second generation e-cigarette was measured at various applied power levels, coil conditions, and e-liquid compositions, including (1) measurements by thermocouple at three e-liquid fill levels (dry, wet-through-wick, and full-wet), three coil resistances (low, standard, and high), and four voltage settings (3-6 V) for multiple coils using propylene glycol (PG) as a test liquid; (2) measurements by thermocouple at additional degrees of coil wetness for a high resistance coil using PG; and (3) measurements by both thermocouple and infrared (IR) camera for high resistance coils using PG alone and a 1:1 (wt/wt) mixture of PG and glycerol (PG/GL). RESULTS: For single point thermocouple measurements with PG, coil temperatures ranged from 322 ‒ 1008°C, 145 ‒ 334°C, and 110 ‒ 185°C under dry, wet-through-wick, and full-wet conditions, respectively, for the total of 13 replaceable coil heads. For conditions measured with both a thermocouple and an IR camera, all thermocouple measurements were between the minimum and maximum across-coil IR camera measurements and equal to 74% ‒ 115% of the across-coil mean, depending on test conditions. The IR camera showed details of the non-uniform temperature distribution across heating coils. The large temperature variations under wet-through-wick conditions may explain the large variations in formaldehyde formation rate reported in the literature for such "top-coil" clearomizers. CONCLUSIONS: This study established a simple and straight-forward protocol to systematically measure e-cigarette coil heating temperature under dry, wet-through-wick, and full-wet conditions. In addition to applied power, the composition of e-liquid, and the devices' ability to efficiently deliver e-liquid to the heating coil are important product design factors effecting coil operating temperature. Precautionary temperature checks on e-cigarettes under manufacturer-recommended normal use conditions may help to reduce the health risks from exposure to toxic carbonyl emissions associated with coil overheating.

A toxicological review of the ethylene glycol series: Commonalities and differences in toxicity and modes of action.

This review summarizes the hazards, exposure and risk that are associated with ethylene glycols (EGs) in their intended applications. Ethylene glycol (EG; CAS RN 107-21-1) and its related oligomers include mono-, di-, tri-, tetra-, and penta-EG. All of the EGs are quickly and extensively absorbed following ingestion and inhalation, but not by the dermal route. Metabolism involves oxidation to the mono- and dicarboxylic acids. Elimination is primarily through the urine as the parent compound or the monoacid, and, in the case of EG, also as exhaled carbon dioxide. All EGs exert acute toxicity in a similar manner, characterized by CNS depression and metabolic acidosis in humans and rodents; the larger molecules being proportionally less acutely toxic on a strict mg/kg basis. Species differences exist in the metabolism and distribution of toxic metabolites, particularly with the formation of glycolic acids and oxalates (OX) from EG and diethylene glycol (DEG); OX are not formed to a significant degree in higher ethylene glycols. Among rodents, rats are more sensitive than mice, and males more sensitive than females to the acute and repeated-dose toxicity of EG. The metabolic formation of glycolic acid (GA), diglycolic acid (DGA), and OX are associated with nephrotoxicity in humans and rodents following single and repeated exposures. However, physiological and metabolic differences in the rate of formation of GA, DGA and OX and their distribution result in EG and DEG causing embryotoxicity in rats, but not rabbits. This rodent-specific sensitivity indicates that EG and its higher oligomers are not anticipated to be embryotoxic in humans at environmentally relevant doses. None of the compounds present developmental toxicity concerns at doses that do not also cause significant maternal toxicity, nor do any of the EGs cause adverse effects on fertility. The EGs are neither genotoxic nor carcinogenic. A read-across matrix is presented, which considers the common and distinct toxicological properties of each compound. It is concluded that EGs pose no risk to human health as a result of their intended use patterns.

A Device-Independent Evaluation of Carbonyl Emissions from Heated Electronic Cigarette Solvents.

OBJECTIVES: To investigate how the two main electronic (e-) cigarette solvents-propylene glycol (PG) and glycerol (GL)-modulate the formation of toxic volatile carbonyl compounds under precisely controlled temperatures in the absence of nicotine and flavor additives. METHODS: PG, GL, PG:GL = 1:1 (wt/wt) mixture, and two commercial e-cigarette liquids were vaporized in a stainless steel, tubular reactor in flowing air ranging up to 318°C to simulate e-cigarette vaping. Aerosols were collected and analyzed to quantify the amount of volatile carbonyls produced with each of the five e-liquids. RESULTS: Significant amounts of formaldehyde and acetaldehyde were detected at reactor temperatures ≥215°C for both PG and GL. Acrolein was observed only in e-liquids containing GL when reactor temperatures exceeded 270°C. At 318°C, 2.03±0.80 µg of formaldehyde, 2.35±0.87 µg of acetaldehyde, and a trace amount of acetone were generated per milligram of PG; at the same temperature, 21.1±3.80 µg of formaldehyde, 2.40±0.99 µg of acetaldehyde, and 0.80±0.50 µg of acrolein were detected per milligram of GL. CONCLUSIONS: We developed a device-independent test method to investigate carbonyl emissions from different e-cigarette liquids under precisely controlled temperatures. PG and GL were identified to be the main sources of toxic carbonyl compounds from e-cigarette use. GL produced much more formaldehyde than PG. Besides formaldehyde and acetaldehyde, measurable amounts of acrolein were also detected at ≥270°C but only when GL was present in the e-liquid. At 215°C, the estimated daily exposure to formaldehyde from e-cigarettes, exceeded United States Environmental Protection Agency (USEPA) and California Office of Environmental Health Hazard Assessment (OEHHA) acceptable limits, which emphasized the need to further examine the potential cancer and non-cancer health risks associated with e-cigarette use.

Assessment of petroleum streams for thyroid toxicity.

The thyroid gland, and its associated endocrine hormones, is a growing area of interest in regulatory toxicology due to its important role in metabolism, growth and development. This report presents a review of the toxicology data on chemically complex petroleum streams for thyroid hormone effects. Toxicological summaries and studies from all available published and un-published sources were considered, drawing upon the European REACH regulatory submissions for 19 petroleum streams, with in depth review of 11 individual study reports and 31 published papers on related products or environmental settings. Findings relevant to thyroid pathology or thyroid hormone homeostasis were specifically sought, summarized, and discussed. A total of 349 studies of 28-days or longer duration were considered in the review, including data on mice, rats, rabbits, dogs, humans, and fish. The thyroid was almost invariably not a target organ in these studies. Three rodent studies did find thyroid effects; one on a jet fuel product (JP-8), and two studies on a heavy fuel oil product (F-179). The JP-8 product differs from other fuels due to the presence of additives, and the finding of reduced T4 levels in mice in the study occurred at a dose that is above that expected to occur in environmental settings (e.g. 2000mg/kg). The finding for F-179 involved thyroid inflammation at 10-55mg/kg that co-occurred with liver pathology in rats, indicating a possible secondary effect with questionable relevance to humans. In the few cases where findings did occur, the polycyclic aromatic hydrocarbon (PAH) content was higher than in related substances, and, in support of one possible adverse outcome pathway, one in-vitro study reported reduced thyroid peroxidase (TPO) activity with exposure to some PAH compounds (pyrene, benzo(k)fluoranthene, and benzo(e)pyrene). However, it could not be determined from the data available for this review, whether these specific PAH compounds were substantially higher in the JP-8 or F-179 products than in studies in which thyroid effects were not observed. Thus, a few products may carry a weak potential to affect the thyroid at high doses in rodents, possibly through secondary effects on the rodent liver or possibly through a pathway involving the inhibition of TPO by specific members of the PAH family. Human epidemiology evidence found weak and inconsistent effects on the thyroid but without identification of specific chemicals involved. Two studies in petroleum workers, which found a lower rate of morbidity and mortality overall, reported a statistically significant increase in thyroid cancer, but the small number of cases could not exclude confounding variables as possible explanations for the statistical findings. Overall, the available data indicates a low potential for thyroid hormone effects from exposure to petroleum streams, especially when the aromatic content is low. Because regulatory studies for most chemicals do not include detailed thyroid function or receptor studies, it remains possible that subclinical effects on this system may exist that were not detectable using conventional pathology or hormone measurements.

Serum concentrations of chlorinated dibenzo-p-dioxins, furans and PCBs, among former phenoxy herbicide production workers and firefighters in New Zealand.

PURPOSE: To quantify serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like compounds in former phenoxy herbicide production plant workers and firefighters, 20 years after 2,4,5-T production ceased. METHODS: Of 1025 workers employed any time during 1969-1984, 430 were randomly selected and invited to take part in a morbidity survey and provide a blood sample; 244 (57%) participated. Firefighters stationed in close proximity of the plant and/or engaged in call-outs to the plant between 1962 and 1987 also participated (39 of 70 invited). Reported here are the serum concentrations of TCDD and other chlorinated dibenzo-dioxins, dibenzofurans, and polychlorinated biphenyls (PCBs). Determinants of the serum concentrations were assessed using linear regression. RESULTS: The 60 men who had worked in the phenoxy/TCP production area had a mean TCDD serum concentration of 19.1 pg/g lipid, three times the mean concentration of the 141 men and 43 women employed in other parts of the plant (6.3 and 6.0 pg/g respectively), and more than 10 times the mean for the firefighters (1.6 pg/g). Duration of employment in phenoxy herbicide synthesis, maintenance work, and work as a boilerman, chemist, and packer were associated with increased serum concentrations of TCDD and 1,2,3,4,7-pentachlorodibenzo-p-dioxin (PeCDD). Employment as a boilerman was also associated with elevated serum concentrations of PCBs. CONCLUSIONS: Occupations in the plant associated with phenoxy herbicide synthesis had elevated levels of TCDD and PeCDD. Most other people working within the plant, and the local firefighters, had serum concentrations of dioxin-like compounds comparable to those of the general population.

Mercury Toxicity and Contamination of Households from the Use of Skin Creams Adulterated with Mercurous Chloride (Calomel).

Inorganic mercury, in the form of mercurous chloride, or calomel, is intentionally added to some cosmetic products sold through informal channels in Mexico and the US for skin lightening and acne treatment. These products have led to multiple cases of mercury poisoning but few investigations have addressed the contamination of cream users' homes. We report on several cases of mercury poisoning among three Mexican-American families in California from use of mercury-containing skin creams. Each case resulted in widespread household contamination and secondary contamination of family members. Urine mercury levels in cream users ranged from 37 to 482 µg/g creatinine and in non-users from non-detectable to 107 µg/g creatinine. Air concentrations of up to 8 µg/m³ of mercury within homes exceeded the USEPA/ATSDR health-based guidance and action level of <1.0 µg/m³. Mercury contamination of cream users' homes presented a multi-pathway exposure environment to residents. Homes required extensive decontamination, including disposal of most household items, to achieve acceptable air levels. The acceptable air levels used were not designed to consider multi-pathway exposure scenarios. These findings support that the calomel is able to change valence form to elemental mercury and volatilize once exposed to the skin or surfaces in the indoor environment.

A toxicological review of the propylene glycols.

The toxicological profiles of monopropylene glycol (MPG), dipropylene glycol (DPG), tripropylene glycol (TPG) and polypropylene glycols (PPG; including tetra-rich oligomers) are collectively reviewed, and assessed considering regulatory toxicology endpoints. The review confirms a rich data set for these compounds, covering all of the major toxicological endpoints of interest. The metabolism of these compounds share common pathways, and a consistent profile of toxicity is observed. The common metabolism provides scientific justification for adopting a read-across approach to describing expected hazard potential from data gaps that may exist for specific oligomers. None of the glycols reviewed presented evidence of carcinogenic, mutagenic or reproductive/developmental toxicity potential to humans. The pathologies reported in some animal studies either occurred at doses that exceeded experimental guidelines, or involved mechanisms that are likely irrelevant to human physiology and therefore are not pertinent to the exposures experienced by consumers or workers. At very high chronic doses, MPG causes a transient, slight decrease in hemoglobin in dogs and at somewhat lower doses causes Heinz bodies to form in cats in the absence of any clinical signs of anemia. Some evidence for rare, idiosyncratic skin reactions exists for MPG. However, the larger data set indicates that these compounds have low sensitization potential in animal studies, and therefore are unlikely to represent human allergens. The existing safety evaluations of the FDA, USEPA, NTP and ATSDR for these compounds are consistent and point to the conclusion that the propylene glycols present a very low risk to human health.

Mainstream smoke emissions of Australian and Canadian cigarettes.

We investigated how mainstream smoke emissions vary and interrelate in 15 Australian and 21 Canadian brands, using public emissions disclosures from 2001. These disclosures provided emission data for 40 hazardous agents under both standard and intensive ISO testing conditions. Our analyses focused on "adjusted emissions" (i.e., emissions per milligram of nicotine yield) for 13 selected agents. Adjusted emissions differed significantly by ISO testing condition for 9 of the 13 selected agents. Intensive condition adjusted emissions were strongly negatively correlated for several agent pairs. Country and manufacturer variables were the strongest predictors of intensive condition adjusted emissions for 8 of the 13 selected agents and significant predictors for all of them. Taken together, these results suggest potential for the intent of emission limits to be undermined by risk swapping (in which one specific exposure is reduced within a group at the cost of another's exposure increasing) and risk shifting (in which a specific exposure is reduced within a group at the cost of that exposure's increasing within another group).

Secondhand tobacco smoke exposure in New Zealand bars: results prior to implementation of the bar smoking ban.

AIMS: To measure secondhand smoke (SHS) levels in New Zealand bars prior to smokefree legislation enacted on 10 December 2004. METHODS: Thirty bars were randomly selected from urban, surburban, and surrounding rural areas of Auckland, Wellington, and Invercargill. Bars were visited (on a Friday or Saturday night for a 3-hour stay between 1800 and 2400 hours) in July/August/September 2004 (winter) and again in October/November 2004 (spring). Each bar was visited by a group of 4 or 5 non-smokers participating in the study. All groups of participants spent a 3-hour block of continuous time in the bar. Saliva samples (approximately 0.5-2 mL) were provided immediately prior to entering the bar as well as 5-15 minutes after leaving the bar. Each group recorded the initial impression of air quality and ventilation, the number of observed lit cigarettes over three 10-minute intervals throughout the evening, and the number of patrons at each interval. In addition, any general comments about the venue (relevant to bar attendance or air quality on the evening) was recorded. Cotinine, the main metabolite of nicotine, was measured in saliva samples using Liquid Chromatography with tandem Mass Spectrometry (LC-MS-MS). RESULTS: In all bars, and in all volunteers, exposure to SHS was evident. Saliva cotinine increased after 3 hours in the bar (mean increase=0.66 ng/mL, SE=0.03 ng/mL, p value of <0.0001). The 30 bars randomly selected provided a good spectrum of SHS exposures, with mean cotinine increasing by approximately 8-fold. Smaller population centres showed greater exposures to SHS. A north-south gradient of exposure was also seen (highest exposures were in Southland). Higher exposures were seen in the winter than in the spring. The objective measures of SHS exposure correlated strongly with the volunteers' subjective observation of ventilation, air quality, and counts of lit cigarettes. One exception was where objective salivary markers indicated that even "seemingly smokefree" venues with "good ventilation" produced discernable levels of SHS exposure. CONCLUSIONS: We have utilised an objective, non-invasive scientific approach to assess SHS smoke exposure in patrons of New Zealand bars. Our results clearly indicate exposure to SHS, with regional and seasonal variation, prior to the introduction of smokefree legislation.

Ethnic differences in nicotine metabolic rate among New Zealanders.

AIMS: To estimate (a) the prevalence of gene variants associated with slow nicotine metabolism in the general Maori population and (b) nicotine intake and metabolic rate in Maori and European smokers. METHODS: The procedure involved (a) genotyping 85 Maori participants for cytochrome P-450 2A6 (CYP2A6) gene variants, which are associated with reduced nicotine metabolic rate (ie CYP2A6*9 and *4); and (b) measuring salivary cotinine (COT) and trans-3'-hydroxycotinine (3-HC) as biomarkers of nicotine intake and metabolic rate in 12 female smokers from the Hawke's Bay Region (6 Maori and 6 European). RESULTS: (a) The frequencies of the slow nicotine metabolising variants, CYP2A6*9 and *4, were significantly higher in Maori compared to European (p<0.01). Indeed, the prevalence of the CYP2A6*9 variant in these Maori was among the highest in the world (approximately 20%). (b) In smokers, the Maori group had approximately 35% lower 3-HC:COT ratios indicating a reduced metabolic rate, as well as 2-fold lower cotinine levels per cigarette smoked, indicating reduced nicotine intake (p<0.05). The CYP2A6*9 allele was significantly more frequent in Maori smokers (70%) compared to Europeans (30%), p=0.03. CONCLUSIONS: The findings of this study provide evidence that Maori are genetically slower nicotine metabolisers compared to Europeans. Although more research is required, this study may help explain ethnic differences in smoking initiation and may also have important implications for smoking cessation programs - since metabolic differences between groups with varying ancestry implies that different optimal dosages of nicotine replacement therapy may be required for successful quitting.

Deaths from poisoning in New Zealand: 2001-2002.

AIMS: To describe the epidemiology and toxicology of poisoning deaths in New Zealand for 2001 and 2002. METHODS: Poisoning mortality data for 2001 and 2002 were collected from the Coronial Service Office (CSO) as part of the New Zealand chemical injury surveillance system. RESULTS: There was 235 and 234 poisoning deaths in 2001 and 2002 respectively, an annual rate of 6.3 [95% CI of 5.5 to 7.1] deaths per 100,000 population for both years. Two-thirds (67.0%) of the deaths were intentional. The 25-44 year age group had the largest number of cases and highest age-specific rate (123 deaths, 11.1 [95% CI: 9.3-13.2] per 100,000 in 2001 and 119 deaths, 10.7 [(95% CI: 9.0-12.8] per 100,000 in 2002). Over two-thirds (68.9%) of the deaths were male. In 2001, the European rate was slightly higher than that for Maori but rates for the two ethnicities were similar in 2002. Geographically, West Coast District Health Board (DHB) had the highest rates. Rates increased with increasing deprivation. Nearly two-thirds (64.3%) of the intentional deaths were attributed to carbon monoxide. Methadone, morphine or heroin, and ethanol were the leading causes of the unintentional deaths. CONCLUSIONS: The rate of poisoning deaths in New Zealand is comparable with other industrial countries as is the prominence of poisoning as a leading method of suicide.

Increase in saliva cotinine after three hours' exposure to second-hand smoke in bars.

OBJECTIVE: To determine whether measurement of cotinine in saliva is a sensitive measure of exposure to second-hand smoke (SHS) among customers in bars. DESIGN: Before/after comparison of saliva cotinine and subjective assessments of SHS. SETTING: Three bars in Wellington, New Zealand, June 2003. PARTICIPANTS: Eleven non-smoking medical students spent three hours in each location. They provided saliva samples before and after the visit, counted numbers of lit cigarettes in each bar, and assessed the smokiness of the venue. Samples were tested for cotinine using liquid chromatography coupled with mass spectrometry. RESULTS: Cotinine levels post-visit were consistently higher than baseline. The mean difference was 1.03 ng/mL with a 95% confidence interval of 0.76-1.30 ng/ mL. Adjustments to post-visit levels for metabolism and clearance of cotinine made very little difference to these results. Males tended to have higher baseline levels than females, and to show smaller increases. The bar with the greatest increase in cotinine was judged to be the smokiest on the basis of averaged cigarette counts and scores for presence of smoke and odour. CONCLUSION: The cotinine in saliva, when tested with the analytic methods described here, provides a means of assessing relatively short-term exposures to SHS.