Project Topics
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Identification of potential hazards of the selected trace metallic elements
Potential adverse effects of the selected metals on biological endpoints/ target organs for the inhalation exposure are explored according to the identified exposure route.
The selection of the metals is detailed in the following part.
Health effects of chronic exposure to Al by the inhalation route
Workers exposed to Al dust showed respiratory effects [48]. Lung problems vary from coughing and occupational asthma to alteration in chest X-rays and pulmonary fibrosis. Animal studies have also revealed adverse respiratory effects, such as the increases in alveolar macrophages and increase in lung weight [48].
TRVs were not constructed for Al because there are doubts on whether the respiratory effects are due to general dust or specifically to the Al in it. Moreover, exposure assessment in occupational studies did not allow calculating an inhalation TRV [48].
On the other hand, occupational studies about workers exposed to Al dusts and fumes reported neuro-toxic symptoms [49,50].
Actual data do not show evidence of carcinogenicity [48].
Health effects of chronic exposure to Cr by the inhalation route
Occupational and especially animal studies have thoroughly assessed the chronic effects of inhalation of Cr and its compounds Cr(III) and Cr(VI). The respiratory system and the skin were confirmed to be the main affected organs [51].
In some specific industries like electroplating, Cr(VI) compounds are used. It was reported that chronic exposure to this particular form of Cr may increase death risk due to non-cancer respiratory illnesses [51]. In our study, we are not considering chromium speciation, but merely the total and/or metallic Cr.
Eye inflammation was also reported from occupational studies where workers were exposed to mists and aerosols of Cr compounds [51].
Metallic Cr and Cr III are not classified as a human carcinogen according to WHO [52]. However, Health Canada [53] has considered total Cr as a carcinogen and established a Tumorigenic Concentration 05 TC05 = 4.6 µg/m3. This value refers to a concentration in the air that is associated with a 5% increase in incidence or mortality due to tumors. It is not a carcinogenic TRV, but a Unit risk can be derived based on this value.
Health effects of chronic exposure to Ni by the inhalation route
Soluble and insoluble nickel compounds showed adverse respiratory effects in rodents. Lung problems include active lung inflammation, alveolar proteinosis and fibrosis [54]. Several occupational and more animal studies confirm the damages in the respiratory tract [4].
Epidemiological studies demonstrated that Ni is a carcinogenic element [55,56]. In 2012, Ni was classified by the WHO as carcinogenic to humans (group 1) [52].
Health effects of chronic exposure to Cu by the inhalation route
Occupational studies have reported that Cu is a respiratory irritant [3] with, among other consequences, pulmonary fibrosis.
Other adverse effects were also reported: gastrointestinal, hematological, hepatic and neurological [3].
Health effects of chronic exposure to Pb by the inhalation route
Many studies on Pb chronic exposure have reported several adverse effects such as hematological, digestive, neurological, renal, cardiovascular, bone and reproductive toxic effect [5,58].
Some studies has indicated probable increases in lung and stomach cancer [5,59].
In 2006, inorganic compounds of Pb were classified by WHO as Probably carcinogenic to humans (stomach cancer) (group 2A) [52].
Moreover, OEHHA [60] has established an Inhalation Unit Risk = 1.2×10-5(μg/m3)-1 for kidney tumors based on animal data.
Health effects of chronic exposure to Zn by the inhalation route
Acute exposure studies have shown respiratory adverse effects. However, there is little information about chronic exposure to zinc dust or fumes and their effects [61]. No TRV was established because of lack of exposure quantification.
Mixture and interactions of metals
Metals are frequently occurring as components of a mixture, especially in occupational settings. That is why it is necessary to take into account the interactions between metals in the hazard characterization analysis [46,47].
TMEs’ joint effects could be distinct from simply additive; they can be synergistic, antagonistic or potentiating [40]. There is another kind of interaction between metals which is named “molecular or ionic mimicry”. It is a competitive interaction when two metals/metalloids are chemically similar; in most cases, a toxic metal replaces an essential metal [40]. Moreover, many MHs form complexes with several proteins in the human body, which could affect their toxicity [40].
The ATSDR has focused on some trace metallic elements and established two interaction profiles about lead, manganese, zinc, and copper, and arsenic, cadmium, chromium and lead [10,63]. Interaction data reports and guidance are limited [40] and relatively old. Thus, we will also explore new published studies.
Toxicokinetics: Physiologically Based PharmacoKinetic models
At the beginning of the study design for this project, in order to explore internal doses in target organs/tissues, we intended to use a PBPK (Physiologically Based PharmacoKinetic) model [64]. Though PBPK models have been used extensively for mixtures such as organic solvents, this is not, to the best of our knowledge, the case for TME mixtures [65]. In spite of the critical need for such a model, particular complexities regarding TMEs prevented their implementation due to the extreme variability of biological half-lives of the main toxic TMEs [66], which range from days (for As) to decades (for Pb). Hence, PBPK models will not be elaborated upon hereafter.
Exposure assessment
Occupational exposure to trace metallic elements
In the general population, the most likely exposure route of TMEs such as Pb, Cu, Zn and Al is the oral pathway. By contrast, in occupational settings, workers are predominantly exposed by inhalation [5]. Thus, we are especially interested in the inhalation pathway and the airborne amount of trace metallic elements in the workplace.
For the inhalation route, metals are generally in solid phase under regular environmental conditions of the atmosphere, so they normally exist in particle phase [40]. However, in occupational circumstances using combustion process (e.g. for melting), metals and metal compounds may also exist as vapors.
Mathematical modeling of occupational exposure to chemicals
Recent developments in modeling allow prediction of exposure to chemicals by using descriptive environmental characteristics and/or the human physiological factors. Since we are dealing with occupational exposures and according to the selection criteria for the study companies (detailed in the first part), inhalation is the main exposure route. We have chosen mathematical models to estimate occupational exposure to airborne pollutants [67,68]. In this framework, a variety of models have been used to predict indoor air pollutants’ concentrations. The models differ in their hypotheses as to (i) pollutant transport mechanisms and (ii) uniformity of the air mixture in the workplace. In our study, these models were executed using the IHMOD “Industrial Hygiene Modeling” software [69,70], which is a model compilation for the calculation of inhalation concentration. It is available from the American Industrial Hygiene Association (AIHA) website [69]. IHMOD currently offers 11 models. The three most commonly-used categories are: (i) the Well Mixed Box, (ii) the Near Field and Far Field model and (iii) the Eddy Diffusion Turbulent model [67].
These predictive models of indoor air concentrations are based on environmental working conditions as well as certain other specific information about the manufacturing process [67]. These models were initially developed for solvents and other volatile compounds, in relation to their physicochemical proprieties. With regards to metals, to the best of our knowledge, similar models were applied only to arc welding processes, in a study in which Boelter et al. calculated field-derived emission rates of total particulate encompassing only iron and manganese [71]. Another newer study [72] have used the well mixed box and Near Field and Far Field model to predict cobalt exposure levels in two job tasks involving powder weighing and mixing. The authors also calculated the emission rates using source air sampling. In the preset study, we aim to broaden the application of these mathematical models to TMEs, as well as to several types of emissions in various production processes.
Well mixed box model
This model suggests a simplified representation of chemicals dispersion. It estimates the air concentration of a completely well mixed room. It means that the pollutant is equally distributed over the room [73].
G: generation rate or emission rate, expressed in mg/min
Q: ventilation rate, expressed in m3/min
V: volume of the air in the workplace, expressed in m3
Cin: pollutant concentration in supply air, expressed in mg/ m3 (generally assumed to be zero)
KL: loss value due to “non-ventilatory” losses (sorption or chemical degradation of the pollutant) [73], expressed in fraction/time. Values ranges from 0 (default: no loss except via ventilation) up to 1.
C0: pollutant concentration in the room at t0, expressed in mg/m3. It is used when there is already a known concentration of the pollutant before the beginning of the emission [73].
After a certain time, the pollutant concentration becomes almost constant as much as the parameters remain the same [73]. It is called the steady state where the predicted concentration reaches a maximum value, and the formula turns into, as below;
Near field –far field model
It is a two-zone model that tries to provide more accurate pollutant estimation for employees working near the emission source. It divides the workplace conceptually into two zones. The Near Field (NF) box includes, by definition, the emission source of the pollutant and the breathing zone of the worker whose exposure is to be estimated [74]. It is conceptualized depending on the exposure situation as a parallelepiped or hemisphere on the floor, on the machine or on work surface. The Far field (FF) is the remaining volume of the workplace, where pollutant concentration is assumed to be lower, and homogeneous over the FF [74].
Table of contents :
GENERAL INTRODUCTION
I. Context and general objectives
I.1. State of the art
I.2. Study site
II. Literature review
II.1. Metallic pollution in Sfax:
II.2. Human health risk assessment
II.2.1. Presentation of the approach
II.2.2. Hazard identification
II.2.2.1. Trace metallic elements
II.2.2.2. Identification of potential hazards of the selected trace metallic elements
a. Health effects of chronic exposure to Al by the inhalation route
b. Health effects of chronic exposure to Cr by the inhalation route
c. Health effects of chronic exposure to Ni by the inhalation route
d. Health effects of chronic exposure to Cu by the inhalation route
e. Health effects of chronic exposure to Pb by the inhalation route
f. Health effects of chronic exposure to Zn by the inhalation route
II.2.2.3. Mixture and interactions of metals
II.2.2.4. Toxicokinetics: Physiologically Based PharmacoKinetic models
II.2.3. Exposure assessment
II.2.3.1. Occupational exposure to trace metallic elements
II.2.3.2. Mathematical modeling of occupational exposure to chemicals
a. Well mixed box model
b. Near field –far field model
c. Parameters calculations
i. Ventilation rate “Q”
ii. The air volume “V”
iii. Generation rate “G”
1) The mass balance method
2) The emission factor method
Emission factors for electric arc welding
Emission factors for electroplating
Emission factors for Resistance sport welding
3) Other model-specific parameters:
II.2.4. Risk characterization methods for chemical mixtures
III. Specific scientific objectives
IV. Bibliography
