Sławomir Czerczak

Calculating the retention of volatile organic compounds in the lung on the basis of their physicochemical properties

In the workplace, deliberate or accidental exposure to volatile organic compounds (VOCs) may occur by ingestion, but more usually through inhalation or dermal contact. The basic model of occupational exposure assumes repeated inhalation exposure during long periods of time, such as 8-h daily, 40-h per working week. Evaluation of the systemic health effects of industrial chemicals can be based on biological levels or internal doses absorbed in dermal or inhalation exposures. The lungs are the primary route of absorption in exposure to gases, vapors, and aerosols. In inhalation exposure, the dose absorbed can be calculated using the following equation: [formula in text] where C, concentration in the air; T, duration of exposure; V, lung ventilation; R, lung retention expressed as % of intake. As lung retention of VOCs has been studied on human volunteers in costly and time-consuming chamber-type experiments, available data are limited. To calculate dosage for the purpose of risk assessment, the default value of 100% is used. As the lung retention of VOCs in lungs can vary from less than 20 to more than 90%, a possibility of predicting the retention values on the basis of blood/air partition coefficients (K(B)) has been investigated. Lung retention data for 36 compounds were obtained from the existing scientific literature. These values derive from human volunteer studies lasting at least 2h. The K(B) values were either the already published experimental data or were calculated based on their physicochemical properties using a published solvation equation. The compounds under study were divided arbitrarily into two groups: water soluble (>10 g/l) and slightly soluble in water (<10 g/l) compounds. For water soluble compounds, the correlation between K(B) and lung retention was high (r=0.75 and 0.73 respectively); this referred both to K(B) values obtained experimentally or calculated in this report. For the compounds slightly soluble in water, the respective values amounted to 0.79 and 0.82. The obtained results indicate that VOC retention in the lung can be calculated solely on the basis of the partition coefficient K(B). As the descriptors used in the solvation equation can be predicted from chemical structure, this finding indicates that it is possible to assess lung retention for any chemical structure of VOC. The model described in the present report can be a practical alternative to the necessity costly and long-lasting chamber-type experiments which are also questionable on ethical grounds.

Calculating the dermal flux of chemicals with OELs based on their molecular structure: An attempt to assign the skin notation.

Our objectives included calculating the permeability coefficient and dermal penetration rates (flux value) for 112 chemicals with occupational exposure limits (OELs) according to the LFER (linear free-energy relationship) model developed using published methods. We also attempted to assign skin notations based on each chemicals molecular structure. There are many studies available where formulae for coefficients of permeability from saturated aqueous solutions (K(p)) have been related to physicochemical characteristics of chemicals. The LFER model is based on the solvation equation, which contains five main descriptors predicted from chemical structure: solute excess molar refractivity, dipolarity/polarisability, summation hydrogen bond acidity and basicity, and the McGowan characteristic volume. Descriptor values, available for about 5000 compounds in the Pharma Algorithms Database were used to calculate permeability coefficients. Dermal penetration rate was estimated as a ratio of permeability coefficient and concentration of chemical in saturated aqueous solution. Finally, estimated dermal penetration rates were used to assign the skin notation to chemicals. Defined critical fluxes defined from the literature were recommended as reference values for skin notation. The application of Abraham descriptors predicted from chemical structure and LFER analysis in calculation of permeability coefficients and flux values for chemicals with OELs was successful. Comparison of calculated K(p) values with data obtained earlier from other models showed that LFER predictions were comparable to those obtained by some previously published models, but the differences were much more significant for others. It seems reasonable to conclude that skin should not be characterised as a simple lipophilic barrier alone. Both lipophilic and polar pathways of permeation exist across the stratum corneum. It is feasible to predict skin notation on the basis of the LFER and other published models; from among 112 chemicals 94 (84%) should have the skin notation in the OEL list based on the LFER calculations. The skin notation had been estimated by other published models for almost 94% of the chemicals. Twenty-nine (25.8%) chemicals were identified to have significant absorption and 65 (58%) the potential for dermal toxicity. We found major differences between alternative published analytical models and their ability to determine whether particular chemicals were potentially dermotoxic.

Evaluation of the TRA ECETOC model for inhalation workplace exposure to different organic solvents for selected process categories

ObjectiveThe aim of this work is to describe the operation principle of the TRA ECETOC model developed using the descriptor system, and the utilization of that model for assessment of inhalation exposures to different organic solvents for selected process categories identifying a given application.MethodMeasurement results were available for toluene, ethyl acetate and acetone in workplace atmosphere in Poland. The following process categories have been postulated: (1) Paints and lacquers factory: use in closed, continuous process with occasional controlled exposure; (2) Shoe factory: roller or brush application of glues; (3) Refinery: use in closed process, no likelihood of exposure. The next step was to calculate the workplace concentration at chosen process categories by applying the TRA ECETOC model.ResultsThe selected categories do not precisely describe the studied applications. Very high concentration values of acetone were measured in the shoe factory, mean 443 ppm. The concentration obtained with the aid of the model is underestimated, ranging from 25.47 to 254.7 ppm, for the case with and without activation of the local exhaust ventilation (LEV), respectively. Estimated concentration at a level corresponding to that of the measured concentration would be possible if the process category involving spraying, e.g., PROC 7 was considered. For toluene and ethyl acetate, the measured concentrations are within the predicted ranges determined with the use of the model when we assume the concentration predicted with active ventilation for the beginning, and the concentration predicted with inactive ventilation for the end of the range.ConclusionsModel TRA ECETOC can be easily used to assess inhalation exposure at workplace. It has numerous advantages, its structure is clear, requires few data, is available free of charge. Selection of appropriate process categories related to the uses identified is guarantee of successful exposure assessment.

Assignment of Skin Notation for Maximum Allowable Concentration (MAC) List in Poland

Organic chemicals from the Polish maximum allowable concentration (MAC) list were analyzed for skin notation. It can be concluded that the dermal dose LD50s determined on experimental animals ought to be adopted as the fundamental criterion for providing a substance with the percutaneous absorption notation in the MAC list. All chemicals with LD50s. value below 1,000 mg/kg should be provided with the Sk index in the MAC list. For other chemicals, a skin notation would be considered when repeated human and dermal application tests have shown significant systemic effects following exposure. When information on the characteristics specified above were not available, physicochemical data required to calculate the flow (solubility, octanol/water partition coefficient, molecular weight) were obtained to consider a skin notation.

A Proposal for Calculating Occupational Exposure Limits for Volatile Organic Compounds Acting as Sensory Irritants on the Basis of Their Physicochemical Properties

A common biological effect of exposure to workplace chemicals is sensory irritation. The ACGIH® threshold limit values (TLVs®) are developed based on data derived from industrial settings as well as experimental human and animal studies. Considering the limited amount of human data and the tendency to reduce the volume of animal testing, there is a need for an alternative method to assess sensory irritation. Nasal pungency involves transfer of a compound through the mucosa into the receptor area. This environment is inhomogeneous, being partly a hydrophobic lipid-like and hydrophilic aqueous-like area. A general equation has been developed that seems satisfactory for explaining the transfer of volatile organic compounds (VOCs) from the gaseous phase to biophases, making it possible to calculate the nasal pungency threshold (NPT). The obtained correlation between log 1/NPT and log TLV for 71 VOCs, which is based exclusively on their irritant properties, indicates that for the compounds that act through a nonreactive mechanism (alcohols, ketones, esters, ethers, aromatic and aliphatic hydrocarbons, amides) the relationship between these values differs from that calculated for compounds that act through a reactive mechanism (aldehydes, allyl compounds, aliphatic amines, benzyl halides, carboxylic acids, acrylates, and mercaptans). The correlation coefficient for nonreactive VOCs is very high (n = 46, r = 0.89), and it appears that the regression equation (log TLV = –0.422 log 1/NPT + 0.309) could be used to predict occupational exposure limits (OELs) for this group of compounds. Regarding reactive VOCs, the correlation coefficient is considerably lower (n = 25, r = 0.32), which implies that some kind of correction for their reactivity would have to be applied to calculate the OEL values.

Acute Poisonings in Poland

The pattern of adolescent and adult poisonings in Poland is presented on the basis of the data from the regional toxicological centers (in-patient treatment centers). Drugs were the most frequent group of chemical substances, responsible for more than 50% of all admissions for acute poisonings. The second most frequent were alcohols with an increase in poisoning by alcohols to about 20% of total poisonings. Carbon monoxide was the third most frequent cause of poisonings. The percentages of poisonings by pesticides, corrosives and metal compounds have been reduced in recent years. The greatest number of lethal outcomes was also due to poisonings by alcohols, drugs, and carbon monoxide.

RD50 value as the criterion for setting maximum admissible levels of occupational exposure to irritants in Poland.

The aim of this work is to analyse Maximum Admissible Concentration (MAC) values proposed for irritants by the Group of Experts for Chemical Agents in Poland, based on the RD50 value. In 1994–2004, MAC values for irritants based on the RD 50 value were set for 17 chemicals. For the purpose of the analysis, 1/10 RD 50,, 1/100 RD50 and the MAC/RD50 ratio were calculated. The determined MAC values are within the 0.01–0.09 RD50 range. The RD50 value is a good rough criterion to set MAC values for irritants and it makes it possible to estimate quickly admissible exposure levels. It has become clear that, in some cases, simple setting the MAC value for an irritant at the level of 0.03 RD 50 may be insufficient to determine precisely the possible hazardto workers’ health. Other available toxicological data, such as NOAEL (No-Observed-Adverse-Effect Level)and LOAEL (Lowest-Observed-Adverse-Effect Level), should always be considered as well.

[Nanosilver--Occupational exposure limits].

Historically, nanosilver has been known as colloidal silver composed of particles with a size below 100 nm. Silver nanoparticles are used in many technologies, creating a wide range of products. Due to antibacterial properties nanosilver is used, among others, in medical devices (wound dressings), textiles (sport clothes, socks), plastics and building materials (paints). Colloidal silver is considered by many as an ideal agent in the fight against pathogenic microorganisms, unlike antibiotics, without side effects. However, in light of toxicological research, nanosilver is not inert to the body. The inhalation of silver nanoparticles have an adverse effect mainly on the liver and lung of rats. The oxidative stress caused by reactive oxygen species is responsible for the toxicity of nanoparticles, contributing to cytotoxic and genotoxic effects. The activity of the readily oxidized nanosilver surface underlies the molecular mechanism of toxicity. This leads to the release of silver ions, a known harmful agent. Occupational exposure to silver nanoparticles may occur in the process of its manufacture, formulation and also usage during spraying, in particular. In Poland, as well as in other countries of the world, there is no separate hygiene standards applicable to nanomaterials. The present study attempts to estimate the value of MAC-TWA (maximum admissible concentration--the time-weighted average) for silver--a nano-objects fraction, which amounted to 0.01 mg/m3. The authors are of the opinion that the current value of the MAC-TWA for silver metallic--inhalable fraction (0.05 mg/m3) does not provide sufficient protection against the harmful effects of silver in the form of nano-objects.

The National Poison Information Center in Poland

OBJECTIVE To describe the national poison information program in Poland. RESULTS There are nine regional poison information centers in Poland associated with acute poisoning wards or diagnostic laboratories. The National Poison Information Center in Lodz prepares information materials (ITOX database, books, periodicals, leaflets, posters) on treatment and prevention to regional and other health care units treating acute poisoning cases and to the general public. The staff of the National Poison Information Center together with the physicians of the Clinic of Acute Poisonings provide a 24 h poison information service accessible to health care units, work safety services, and the general public.

Testing of the composition of e-cigarette liquids – Manufacturer-declared vs. true contents in a selected series of products

BACKGROUND Electronic cigarettes are currently in common use. However, in Poland there is no specific legislation governing the sale of these products. At the same time, no information has been made public about the hazards e-cigarettes pose to the users and bystanders - passive smokers. The aim of the study was to determine the qualitative composition of the analyzed liquid, which is an essential element of regulating the distribution of such cigarettes. MATERIAL AND METHODS Under this study the method for determining the composition of e-cigarette liquids was developed. This method employs gas chromatography with mass spectrometry (GC-MS). Levels of nicotine and flavoring components were determined in 50 e-liquid samples. The results were compared with the information provided by the manufacturer on the packaging. RESULTS The applied method of qualitative determination helped to identify the main ingredients, such as nicotine and propylene glycol (PG). Propylene glycol was found to be present in all liquids, because it was used as the solvent for nicotine and flavors. There was a good agreement between the declared and the determined content of nicotine in the analyzed samples. The agreement was considerably poorer for the remaining e-liquid ingredients, mainly flavors. CONCLUSIONS There was no agreement between the flavor substances specified by the manufacturer and aroma identified in the e-cigarette liquid, which may pose a risk to users of e-cigarettes, particularly those susceptible to allergies. Several unsaturated aliphatic alcohols and aldehydes found to be present in the liquids, unstable at elevated temperatures, may be more harmful to the smoker than the original compounds. Therefore, it is essential to implement in Poland the legal provisions regarding e-cigarettes. Med Pr 2016;67(2):239-253.