Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry

Imed Gargouri, Fatma Omrane and Moncef Khadhraoui

### Abstract

Organic solvents (OS) are widely used in Tunisian footwear industry; however, there are no data related to employees' exposure. The objective of this study was therefore to adjust analytical methods in our laboratory for exposure assessment purposes. The predominant solvents are acetone, cyclohexane, hexane, methyl ethyl ketone, and toluene. Eighteen companies benefited from 55 airborne and 190 urine samples. Quantification of solvents and their metabolites was achieved by analytical methods that were adapted and validated in our laboratory. Airborne solvents were determined using gas chromatography (GC-FID). Urinary solvents or metabolites were measured either by GC or high-performance liquid chromatography (HPLC). Validation criteria were determined and used to judge the methods reliability. For airborne solvents, the concentrations exceeding the threshold limit value are mainly for hexane. For urines, the hippuric acid concentrations exceeded the biological limit value in semi-industrial process. Surprisingly, trans, transmuconic acid was found in industrial and artisanal processes even though benzene was not among the used products. GC and HPLC methods have been adjusted, optimized, and effectively used to quantify OS and their metabolites in airborne and urine samples. Thus, a process of occupational risk assessment via a biotoxicological and airborne monitoring for solvents is now set.

Keywords: solvent exposure, chromatographic methods, risk assessment, indoor air, biomonitoring

### 1. Introduction

In the modern world, chemicals are integrated almost into every part of human life and activity. Their handling especially in huge quantities represents in some cases a health risk. In this context, organic solvents are regarded among the main chemical pollutants of the family called volatile organic compounds [1, 2–5] commonly used in the industrial sectors. Indeed, these products are widely employed in several fields and included in the composition of various products such as paints, inks, glues, pesticides, degreasers, and thinners. However, due to their readily volatilization, these solvents can be easily released into the atmosphere during manufacturing, storage, transportation, and application, which facilitate their inhalation by human and causing thus adverse health effects. In some cases, the inhaled chemical even undergoes biotransformations and may create more or less reactive

intermediates leading to intoxication. Therefore, the assessment of human exposure to organic solvents in workplaces where they are handled in great quantities is of utmost importance for elucidation of human risks.

Among the chemical risks (CR) identified in Tunisian footwear manufacturing industry, organic solvents occupy by far the first place. However, despite the huge consumed quantities, exposure data of employees to these solvents in this area are almost absent. Actually, the prevention of occupational risks, especially for CR, is based on risk assessment following the procedures set by the regulations [4–8]. Nonetheless, the Tunisian health regulations [7, 8] have provided no requirement for entrepreneurs to conduct risk assessments via indoor air measurements in the workplaces or any biological exposure monitoring. We think that one of the reasons could be related to the lack of specialized laboratories in the field of metrology and health exposure assessment, since foreign companies engaged in such assessment are obliged to send their samples abroad.

To do so and overcome this shortcoming, the development of protocols and the validation of analytical methods to quantify the solvents and their metabolites in human fluids can partly solve the problem of exposure to OS. In the current case, the developed methods were used to evaluate the airborne content in terms of solvents such as acetone, cyclohexane, n-hexane, MEK, toluene, and trichloroethylene in shoe manufacturing companies in the city of Sfax. The detection and the quantification of their respective metabolites were also addressed.

Within this context, according to the guidelines, the most used technique is the gas chromatography (GC) coupled to a mass spectrometry detector [9–11]. The urinary metabolites of OS are also assessed by chromatographic methods; liquid chromatography (HPLC) [12, 13] and gas chromatography (GC) [14], each coupled to mass spectrometry, remain by far the most suitable methods for solvent and metabolite quantification. However, in our laboratory the GC is coupled with flame ionization FID detector. In this investigation, and as mentioned earlier, our main focus is to adapt the analytical method with our instrument and to validate GC-FID and HPLC methods to be used later on in routine analysis of OS and their respective urinary metabolites, in workplaces, such as shoe industry, with the ultimate aim to assess chemical exposures and health adverse impacts.

trichlorethylene [4, 17, 18]. They were subjected to an airborne quantification in addition to their metabolites which were measured in urine worker samples [19]. Although benzene was not identified in the composition of the products, for security reasons, it was systematically investigated via its metabolite trans, trans-

(a) Individual sampling of indoor air exposure. (b) Stationary sampling of the workplace's atmosphere.

Process Industrial Semi-industrial Artisanal Total

Employees 751 48 350 1149

Employees 122 48 60 230

The discovered population (2005) Companies 26 6 60 92

Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry

DOI: http://dx.doi.org/10.5772/intechopen.86295

The selected sample (2008) Companies 6 6 10 22

The solvent exposure assessment was performed along 15 weeks, based on some

To measure personal exposure, an air sampling holder was fixed near the respiratory zone of each volunteer worker (Figure 1) [23–27]. The sampling method and equipments have already been described [16]. These samples were taken in the middle of the week on Wednesdays or Thursdays depending on the type of the

Result comparisons of the analyzed samples were carried out in reference to average values of exposure (TLV) calculated over a reference period of 8 hours/day

In order to quantify solvent metabolites, 190 employees among 230 involved in shoe manufacturing, belonging to 22 companies, have benefited from urinary sampling. These samples were taken by the weekends and at the end of the work shifts:

former studies [5, 21, 22] and via several steps that are detailed in our previous

company's manufacturing process and installation locations (Table 2).

muconic acid in urine [7, 8, 20].

publication [16].

81

Table 1.

Figure 1

Footwear companies.

2.3 Sampling and analytical methods

and 39 hours/week (Table 7) [7, 8, 17, 28, 29].

### 2. Material and methods

### 2.1 The shoe manufacturing process and sampling of the footwear companies

Actually, in Tunisia, the shoe industry, despite its mechanization, remains a labor industry where about 150 operations are required to make a pair of shoes. The shoe manufacturing steps are already presented in previous publications [15, 16].

The footwear manufacturing companies were identified and classified under three groups according to their manufacturing processes: industrial, semiindustrial, and artisanal. The classification is previously detailed [16] and briefly summarized in Table 1.

### 2.2 Selection of solvents and their metabolites to be quantified

Following the identification of solvents encompassed in the composition of products handled (glues, thinners, and strippers) in shoemaking conducted during the first half of 2008 in Sfax region, we were able to identify the most predominant solvents such as acetone, cyclohexane, hexane, methyl ethyl ketone, toluene, and

Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry DOI: http://dx.doi.org/10.5772/intechopen.86295


#### Table 1.

intermediates leading to intoxication. Therefore, the assessment of human exposure to organic solvents in workplaces where they are handled in great quantities is of

Among the chemical risks (CR) identified in Tunisian footwear manufacturing industry, organic solvents occupy by far the first place. However, despite the huge consumed quantities, exposure data of employees to these solvents in this area are almost absent. Actually, the prevention of occupational risks, especially for CR, is based on risk assessment following the procedures set by the regulations [4–8]. Nonetheless, the Tunisian health regulations [7, 8] have provided no requirement for entrepreneurs to conduct risk assessments via indoor air measurements in the workplaces or any biological exposure monitoring. We think that one of the reasons could be related to the lack of specialized laboratories in the field of metrology and health exposure assessment, since foreign companies engaged in such assessment

To do so and overcome this shortcoming, the development of protocols and the validation of analytical methods to quantify the solvents and their metabolites in human fluids can partly solve the problem of exposure to OS. In the current case, the developed methods were used to evaluate the airborne content in terms of solvents such as acetone, cyclohexane, n-hexane, MEK, toluene, and trichloroethylene in shoe manufacturing companies in the city of Sfax. The detection and the

Within this context, according to the guidelines, the most used technique is the gas chromatography (GC) coupled to a mass spectrometry detector [9–11]. The urinary metabolites of OS are also assessed by chromatographic methods; liquid chromatography (HPLC) [12, 13] and gas chromatography (GC) [14], each coupled to mass spectrometry, remain by far the most suitable methods for solvent and metabolite quantification. However, in our laboratory the GC is coupled with flame ionization FID detector. In this investigation, and as mentioned earlier, our main focus is to adapt the analytical method with our instrument and to validate GC-FID and HPLC methods to be used later on in routine analysis of OS and their respective urinary metabolites, in workplaces, such as shoe industry, with the ultimate aim to

2.1 The shoe manufacturing process and sampling of the footwear companies

Actually, in Tunisia, the shoe industry, despite its mechanization, remains a labor industry where about 150 operations are required to make a pair of shoes. The shoe manufacturing steps are already presented in previous publications [15, 16]. The footwear manufacturing companies were identified and classified under

Following the identification of solvents encompassed in the composition of products handled (glues, thinners, and strippers) in shoemaking conducted during the first half of 2008 in Sfax region, we were able to identify the most predominant solvents such as acetone, cyclohexane, hexane, methyl ethyl ketone, toluene, and

three groups according to their manufacturing processes: industrial, semiindustrial, and artisanal. The classification is previously detailed [16] and briefly

2.2 Selection of solvents and their metabolites to be quantified

quantification of their respective metabolites were also addressed.

assess chemical exposures and health adverse impacts.

2. Material and methods

summarized in Table 1.

80

utmost importance for elucidation of human risks.

Standards, Methods and Solutions of Metrology

are obliged to send their samples abroad.

Footwear companies.

#### Figure 1

(a) Individual sampling of indoor air exposure. (b) Stationary sampling of the workplace's atmosphere.

trichlorethylene [4, 17, 18]. They were subjected to an airborne quantification in addition to their metabolites which were measured in urine worker samples [19]. Although benzene was not identified in the composition of the products, for security reasons, it was systematically investigated via its metabolite trans, transmuconic acid in urine [7, 8, 20].

### 2.3 Sampling and analytical methods

The solvent exposure assessment was performed along 15 weeks, based on some former studies [5, 21, 22] and via several steps that are detailed in our previous publication [16].

To measure personal exposure, an air sampling holder was fixed near the respiratory zone of each volunteer worker (Figure 1) [23–27]. The sampling method and equipments have already been described [16]. These samples were taken in the middle of the week on Wednesdays or Thursdays depending on the type of the company's manufacturing process and installation locations (Table 2).

Result comparisons of the analyzed samples were carried out in reference to average values of exposure (TLV) calculated over a reference period of 8 hours/day and 39 hours/week (Table 7) [7, 8, 17, 28, 29].

In order to quantify solvent metabolites, 190 employees among 230 involved in shoe manufacturing, belonging to 22 companies, have benefited from urinary sampling. These samples were taken by the weekends and at the end of the work shifts:


Table 2.

The moments of interventions in the companies.


Table 3.

Sample of participating companies to airborne and biomonitoring interventions.

on Friday or Saturday afternoon (Tables 2 and 3) [30–33]. These urine samples were performed with reference to the biological limit values (Table 7) [16, 34–36].

> thickness = 0.25 μm). To optimize this method, different conditions were tested such as oven temperature, split/splitless injections, injected volume, and column

Solvent Acetone n-Hexane MEK Cyclohexane Trichlorethylene Toluene Retention time (min) 6.2 7.7 8.3 9.4 10.9 15.3 Area peak 882337 3552515 20758 2107460 892254 2678766 Concentration (mg/l) 14.10 11.78 14.37 13.89 26.16 15.48

Retention time (min) concentration (mg/l) and surface area of peaks of the various solvents.

Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry

DOI: http://dx.doi.org/10.5772/intechopen.86295

Depending on the nature of the metabolites of solvents, the following techniques

were used for their quantification (Figure 3 and Table 6) [37, 44–49]:

Chromatograms of two standard injected under the same conditions as analytical samples.

Chromatogram of a standard injected in the same analysis conditions as those of the samples.

type and length [37–39].

Table 5.

Figure 2.

Figure 3.

83

2.3.1.2 Dosing the metabolites of target solvents in urine

### 2.3.1 Toxicological analysis protocols

### 2.3.1.1 Dosing the target solvents in the indoor air

After desorption in 5 ml of carbon disulfide (Fluka®, Ref. 84710), the activated charcoal was analyzed by gas chromatography coupled with flame ionization detector (GC-FID) using an external calibration mode (Tables 4 and 5, Figure 2): (i) SHI MADZU® chromatograph, GC-9A, and (ii) capillary column Hewlett-Packard® HP-5MS (L = 60 m, inner diameter = 0.25 mm, film


#### Table 4.

Preparation and analytical targets solvents "activated charcoal tube: 200/800" [26, 35–37, 44].

Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry DOI: http://dx.doi.org/10.5772/intechopen.86295


Table 5.

Retention time (min) concentration (mg/l) and surface area of peaks of the various solvents.


#### Figure 2.

on Friday or Saturday afternoon (Tables 2 and 3) [30–33]. These urine samples were performed with reference to the biological limit values (Table 7) [16, 34–36].

Sample of participating companies to airborne and biomonitoring interventions.

Leave weekly Airborne sampling Urinary sampling

Wednesday (Morning)

Thursday (morning) Friday

Saturday

After desorption in 5 ml of carbon disulfide (Fluka®, Ref. 84710), the activated

Cyclohexane (C6H12)

56.3°C 68.7°C 79.6°C 80.7°C 87.3°C 110.6°C 88°C

Cyclohexane (C6H12)

Trichlorethylene (C2HCl3)

Trichlorethylene (C2HCl3)

Toluene (C7H8)

Toluene (C7H8)

Benzene (C6H6)

Benzene (C6H6)

charcoal was analyzed by gas chromatography coupled with flame ionization detector (GC-FID) using an external calibration mode (Tables 4 and 5, Figure 2):

(i) SHI MADZU® chromatograph, GC-9A, and (ii) capillary column Hewlett-Packard® HP-5MS (L = 60 m, inner diameter = 0.25 mm, film

> MEK (C4H8O)

5 ml for validation area and 1.5 ml for the control area

Materials Volumetric flasks, rocking stirring, 10 ml vials of glass, micropipette

MEK (C4H8O)

Preparation and analytical targets solvents "activated charcoal tube: 200/800" [26, 35–37, 44].

30 min at relatively low temperature

Method GC-FID (Gas chromatography with flame ionization detection)

n-Hexane (C6H14)

2.3.1 Toxicological analysis protocols

Solvent Acetone

Stirring (min)

External standard Acetone

Volatilization temperature

MEK: methyl ethyl ketone.

Table 4.

82

Desorption Solvent Carbon disulfide Amount (ml)

Process manufacturing

Table 2.

Table 3.

2.3.1.1 Dosing the target solvents in the indoor air

(C3H6O)

Mode Manual agitation

(C3H6O)

n-Hexane (C6H14)

Installation location

Standards, Methods and Solutions of Metrology

The Medina (old town)

The moments of interventions in the companies.

NB.: Semi-industrial companies: some in the Medina and other industrial areas.

Industrial Industrial zone Saturday (afternoon) and

Sunday

Monday

(afternoon) Semi-industrial

(afternoon) Artisanal

Sunday (afternoon) and

Companies Class Identified Planned Realized Airborne measurements Urinary sampling Industrial 1 26 6 4 17 105 Semi-industrial 2 6 6 5 23 60 Artisanal 3 60 10 10 15 25

Total 92 22 18 55 190

Chromatogram of a standard injected in the same analysis conditions as those of the samples.

thickness = 0.25 μm). To optimize this method, different conditions were tested such as oven temperature, split/splitless injections, injected volume, and column type and length [37–39].

### 2.3.1.2 Dosing the metabolites of target solvents in urine

Depending on the nature of the metabolites of solvents, the following techniques were used for their quantification (Figure 3 and Table 6) [37, 44–49]:



### Table 6.

Retention time (min) concentration (mg/l) and peak area of the different metabolites.

	- SHI MADZU® chromatograph GC-17A
	- Capillary column Hewlett-Packard® HP-1 (L = 60 m, inner diameter = 0.25 mm, film thickness = 1 μm)
	- Chromatograph agilent 1100 series
	- Column shim-pack CLC-ODS (n) 15 cm

As mentioned before, HPLC and GC conditions were optimized, and validation criteria (repeatability, detection limit, linearity, and recovery test) were evaluated.

### 2.4 Biometrological exposure limit values

In the absence of Tunisian exposure guideline values for the workplace air quality and biological samples [7, 8], we referred to the French, American, and/or German values. Then, we adopted the most severe among them as reference values (Table 7) [17, 28–31, 50, 51].

More specifically, the air concentrations were compared to threshold limit value-time-weighted average (TLV-TWA) for solvents.

For the biological exposure indices (BEI) related to metabolites (Table 7) [16, 34–36], they were as follows: acetone for acetone, 2,5-hexanedione for hexane, 1,2-cyclohexanediol for cyclohexane, methyl ethyl ketone for methyl ethyl ketone, hippuric acid for toluene, and trans, trans-muconic acid for benzene [32, 52, 53].

### 3. Results

#### 3.1 Airborne solvent quantification

All conducted measurements in different companies showed that the exposure to solvents varies from one process to another and from one station to another [16]. Direct results of airborne concentration measurements of the solvents are published in our previous publication [16]. Average airborne concentrations of hexane are particularly high especially with overruns of the TLV in upper worker, sole maker, and finishing positions in all processes except for the artisanal type 2. For the other

1CAS, chemical abstract service; 2EU, European Union; 3ACGIH, American Conference of

85

Gemeinschaft; 6VME, exposure average value calculated with respect to a reference period of 8 hours;

week); 8ppm, parts per million by volume of air; 9VGF, value guide French; 10EIB, biological exposure indices; 11BAT, Bioloischer

Table 7. Values of airborne and biological exposure limits for solvents studied [9, 10, 13, 17, 25, 27, 28].

Governmental

 Industrial Hygienists; 4MAK,

7TLV-TWA,

time-weighted

 average (weighted average values over 8 hours per day and 40 hours per

Arbeitsstoff-Toleranz-Wert

 (biological values tolerated in the workplace).

maximum-Arbeitsplatz

konzentration;

 5DFG, Deutsche Forchungs-

Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry

DOI: http://dx.doi.org/10.5772/intechopen.86295


1CAS, chemical abstract service; 2EU, European Union; 3ACGIH, American Conference of Governmental Industrial Hygienists; 4MAK, maximum-Arbeitsplatz konzentration; 5DFG,Gemeinschaft; 6VME, exposure average value calculated with respect to a reference period of 8 hours; 7TLV-TWA, time-weighted average (weighted average values over 8 hours per dayweek); 8ppm, parts per million by volume of air; 9VGF, value guide French; 10EIB, biological exposure indices; 11BAT, Bioloischer Arbeitsstoff-Toleranz-Wert (biological values tolerated

 Deutsche Forchungs-

 and 40 hours per

 in the workplace).

### Table 7.

 Values of airborne and biological exposure limits for solvents studied [9, 10, 13, 17, 25, 27, 28].

### Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry DOI: http://dx.doi.org/10.5772/intechopen.86295

• Either by GC-FID:

Retention time (min)

Concentration (mg/l)

Table 6.

Metabolites Acetone 2,5-

Standards, Methods and Solutions of Metrology

• Or by HPLC:

• SHI MADZU® chromatograph GC-17A

Hexanedione

• Chromatograph agilent 1100 series

2.4 Biometrological exposure limit values

(Table 7) [17, 28–31, 50, 51].

3.1 Airborne solvent quantification

3. Results

84

• Column shim-pack CLC-ODS (n) 15 cm

value-time-weighted average (TLV-TWA) for solvents.

diameter = 0.25 mm, film thickness = 1 μm)

Retention time (min) concentration (mg/l) and peak area of the different metabolites.

• Capillary column Hewlett-Packard® HP-1 (L = 60 m, inner

GC-FID HPLC

Area peak 379899 762130 176371 29836 2062.5 31054.3

MEK 1,2 and 1,4-

Cyclohexandiol

9.333 12.204 25.401 31.266 5.6 8.5

3507.1 3614 957 174.4 13.5 1214

Trans, transmuconic acid Hippuric acid

As mentioned before, HPLC and GC conditions were optimized, and validation criteria (repeatability, detection limit, linearity, and recovery test) were evaluated.

In the absence of Tunisian exposure guideline values for the workplace air quality and biological samples [7, 8], we referred to the French, American, and/or German values. Then, we adopted the most severe among them as reference values

More specifically, the air concentrations were compared to threshold limit

For the biological exposure indices (BEI) related to metabolites (Table 7) [16, 34–36], they were as follows: acetone for acetone, 2,5-hexanedione for hexane, 1,2-cyclohexanediol for cyclohexane, methyl ethyl ketone for methyl ethyl ketone, hippuric acid for toluene, and trans, trans-muconic acid for benzene [32, 52, 53].

All conducted measurements in different companies showed that the exposure to solvents varies from one process to another and from one station to another [16]. Direct results of airborne concentration measurements of the solvents are published in our previous publication [16]. Average airborne concentrations of hexane are particularly high especially with overruns of the TLV in upper worker, sole maker, and finishing positions in all processes except for the artisanal type 2. For the other

quantified solvents (acetone, cyclohexane, methyl ethyl ketone, and toluene), they were relatively high without exceeding the TLV.

of toluene and benzene. The parameters are the number of urine samples collected (n) per workstation and sex, the arithmetic mean of urinary concentrations of

The hippuric acid was particularly high with average exceeding the TLV for certain employees in the semi-industrial process for the majority of workstations, including the cutting. We noted particularly high values of the toluene in type 2

The trans, trans-muconic acid was highlighted in the industrial process and artisanal type 1 with average ranging from 1.2 to 3.1 mg/g creatinine, far exceeding the TLV.

We had to suffer from some delay in achieving our airborne sampling and therefore an impact on the quality of our data because of different difficulties. In large part, it is due to the heaviness of administrative procedures to follow in Tunisia for the acquisition of scientific equipments. We have waited for over a year to have the air sampling pumps (May 2006, making contact with the supplier until June 2007, receipt of the order). Meanwhile, we adjusted the analytical analysis protocols for solvents and their metabolites. It required bibliographical research and repeated tests in the laboratory as it was not a directed technology transfer (North-South) [22, 39–43]. We were able to quantify the airborne samples with activated charcoal tubes after their storage at 4°C, and that was achieved within a short time. We did not have that opportunity for urine samples, and we had to freeze them since we were neither (and technicians) capable of performing these dosages nor owning sufficient material (one GC). This GC had also some technical problems, and we have not been able to use these results since conservation methods have not been respected. Only the results of the metabolites made by HPLC (hippuric acid and

This material is of great interest to develop this type of action and toxicological metrology in the Sfax region. Indeed, this is the first time that there has been the acquisition of active sampling materials in the field of occupational health in Tunisia. Moreover, it is also the first opportunity on the establishment of a structured approach in occupational and environmental toxicology through GEET laboratory (previously known as 3E) in a new theme "impact of hazardous substances on

For a dozen years, the use of solvents is undergoing a revolution, because of

occupational risk prevention constraints but mostly because of regulatory

artisans, while the TLV was not exceeded in the industrial process.

Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry

Data on urinary dosage of metabolites of the four solvents, acetone, 2,5-hexandione, methyl ethyl ketone, and 1,2-cyclohexandiol, which are the respective biomarkers of acetone, hexane, cyclohexane, and MEK were not usable

metabolites, and the range of concentrations.

DOI: http://dx.doi.org/10.5772/intechopen.86295

3.2.2 Dosage of metabolites by GC

due to a technical problem in GC.

4. Comments and discussion

trans, trans-muconic acid) were analyzed.

4.2 Airborne sampling equipments

environment and human health."

87

4.3 Biometrological measurements

4.1 Reviews and bias

### 3.2 Dosage of urinary metabolites

We limited ourselves to dosing urine samples collected during the first period: a stage where companies are on average activity (from 28 May to 28 July 2008).

### 3.2.1 Dosage of metabolites by HPLC

Table 8 summarizes the main data urinary dosages of two solvent metabolites: the hippuric acid and trans, trans-muconic acid that are the respective biomarkers


Table 8. Assays of urinary hippuric acid and trans, trans-muconic acid according to workstation. Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry DOI: http://dx.doi.org/10.5772/intechopen.86295

of toluene and benzene. The parameters are the number of urine samples collected (n) per workstation and sex, the arithmetic mean of urinary concentrations of metabolites, and the range of concentrations.

The hippuric acid was particularly high with average exceeding the TLV for certain employees in the semi-industrial process for the majority of workstations, including the cutting. We noted particularly high values of the toluene in type 2 artisans, while the TLV was not exceeded in the industrial process.

The trans, trans-muconic acid was highlighted in the industrial process and artisanal type 1 with average ranging from 1.2 to 3.1 mg/g creatinine, far exceeding the TLV.

### 3.2.2 Dosage of metabolites by GC

quantified solvents (acetone, cyclohexane, methyl ethyl ketone, and toluene), they

We limited ourselves to dosing urine samples collected during the first period: a

Table 8 summarizes the main data urinary dosages of two solvent metabolites: the hippuric acid and trans, trans-muconic acid that are the respective biomarkers

> Quilting Man 4 124.3–222.3 159.1 0.8–3.5 1.7 Upper worker Man 2 80.8–242.2 161.5 0.7–1.6 1.2

> Sole maker Man 5 57.0–359.7 192.7 0.2–6.0 3.1 Finish Man 2 67.7–138.0 102.8 1.7–1.9 1.8

> Serigraph Women 1 — 180.3 — 1.6

Chopped off Man 2 207.3–6768.1 3487.7 0.1–0.7 0.4 Quilting Man 1 — 749.3 — 0.0 Upper worker Man 9 380.4–9322.3 3112.7 00–03 0.1

Sole maker Man 11 546.7–7277.2 2349.4 0.0–0.4 0.1 Finish Man 2 2178.0–2609.5 2393.8 0.0–0.4 0.2

Upper worker Man 4 295.8–1775.0 903.4 0.0–2.2 1.5 Sole maker Man 5 57.5–4582.7 1086.3 0.1–2.9 1.6

Assays of urinary hippuric acid and trans, trans-muconic acid according to workstation.

(mg/g creatinine)

Women 5 33.9–352.5 190.9 0.9–4.4 2.4 Total 7 33.9–352.5 182.5 0.7–4.4 2.1

Women 3 71.5–381.7 194.7 1.5–5.5 2.8 Total 5 67.7–381.7 158.0 1.5–5.5 2.4

Women 3 25.5–5358.6 3523.9 00–02 0.1 Total 12 25.5–9322.3 3215.5 0.0–0.3 0.1

Total 7 0.0–2823.9 1482.2 0.0–0.4 0.1

Man 4 440.2–4784.5 3292.5 0.0–0.2 0.1

0.0

0.0

Women 5 0.0–2823.9 1117.6 From 0.0 to

Trans, trans-muconic acid (mg/g creatinine)

Range Average Range Average

stage where companies are on average activity (from 28 May to 28 July 2008).

were relatively high without exceeding the TLV.

Process Working post Operator n Hippuric acid

3.2 Dosage of urinary metabolites

Standards, Methods and Solutions of Metrology

3.2.1 Dosage of metabolites by HPLC

Industrial "<sup>1</sup> company" 13 men and 9 women

Semi-industrial

Artisanal "6 companies"

Table 8.

86

13 men

Upper worker/sole

maker

 "<sup>3</sup> business" 25 men and 8 women

Data on urinary dosage of metabolites of the four solvents, acetone, 2,5-hexandione, methyl ethyl ketone, and 1,2-cyclohexandiol, which are the respective biomarkers of acetone, hexane, cyclohexane, and MEK were not usable due to a technical problem in GC.

### 4. Comments and discussion

#### 4.1 Reviews and bias

We had to suffer from some delay in achieving our airborne sampling and therefore an impact on the quality of our data because of different difficulties. In large part, it is due to the heaviness of administrative procedures to follow in Tunisia for the acquisition of scientific equipments. We have waited for over a year to have the air sampling pumps (May 2006, making contact with the supplier until June 2007, receipt of the order). Meanwhile, we adjusted the analytical analysis protocols for solvents and their metabolites. It required bibliographical research and repeated tests in the laboratory as it was not a directed technology transfer (North-South) [22, 39–43].

We were able to quantify the airborne samples with activated charcoal tubes after their storage at 4°C, and that was achieved within a short time. We did not have that opportunity for urine samples, and we had to freeze them since we were neither (and technicians) capable of performing these dosages nor owning sufficient material (one GC). This GC had also some technical problems, and we have not been able to use these results since conservation methods have not been respected. Only the results of the metabolites made by HPLC (hippuric acid and trans, trans-muconic acid) were analyzed.

#### 4.2 Airborne sampling equipments

This material is of great interest to develop this type of action and toxicological metrology in the Sfax region. Indeed, this is the first time that there has been the acquisition of active sampling materials in the field of occupational health in Tunisia. Moreover, it is also the first opportunity on the establishment of a structured approach in occupational and environmental toxicology through GEET laboratory (previously known as 3E) in a new theme "impact of hazardous substances on environment and human health."

#### 4.3 Biometrological measurements

For a dozen years, the use of solvents is undergoing a revolution, because of occupational risk prevention constraints but mostly because of regulatory

requirements for environmental protection. These regulatory changes led to changes in the nature of the applied solvents and how to use them [17, 29, 54]. Meanwhile the number of exposed workers is growing in Tunisia. This is confirmed on the international level (in France): the SUMER 2003 survey showed that the number of employees exposed to solvents has increased since 1994 from 12.2 to 14.7% mainly in the chemical industry [2].

in this sector. However, we know that exposure to solvents is not constant over time and varies according to the task performed and the utilized process. Therefore, the investigation on exposure needs not only the average exposure in comparison with TLV but also to identify the polluting phases in order to determine the short-term

Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry

DOI: http://dx.doi.org/10.5772/intechopen.86295

In the footwear manufacturing sector, following the identification phase of the used solvents and the highlighting of overruns in airborne concentrations of some hazardous products, we plan to focus on the carcinogenic characteristic of certain preparations and especially their potential toxicity for reproduction, since we noted the increase of female presence in the shoe manufacturing sector and some cases of

The authors thank the University of Sfax for financial support.

Authors have declared that no conflict of interest exists.

Imed Gargouri\*, Fatma Omrane and Moncef Khadhraoui

\*Address all correspondence to: imed.gargouri@fmsf.rnu.tn

School of Engineering, University of Sfax, Tunisia

provided the original work is properly cited.

Laboratory "Environmental Engineering and EcoTechnology" LR16ES19, National

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

exposure.

couple sterility.

Acknowledgements

Conflict of interest

Author details

89

Thus, risk assessment studies in various sectors using solvents were started, but the shoe manufacturing sector remained unexplored. This is the case of the study of Poirot and Hubert-Pelle [17] that evaluated exposures to solvents with airborne samples in various industrial activities but not in the manufacture of glue.

If these airborne sampling and biotoxicological analyses were made for the first time in the sector of footwear manufacturing in Sfax, they included a sample of companies from the three manufacturing processes (industrial, semi-industrial, and artisanal); this was preceded by a preliminary risk assessment along with job tasks examinations and an inventory of the handled products [5, 6]. This risk assessment could be improved due to the experience we have gained and with the best knowledge of the sector and the risk prioritization in it.

The results of airborne sampling have confirmed that the existing gaps between the different shoe companies and different workstations were generally those that were indirectly estimated by the workstations observations.

All the conducted sampling in the companies indicates that employees' exposure to organic solvents is quite variable depending on the performed job task.

The hippuric acid was highlighted in the urines of some employees with exceedances of the limit value; however, the TLV of toluene has not been exceeded in the companies. This could be explained by a dermal exposure, especially since we have not recorded the use of gloves by workers when they handle preparations used in shoe manufacturing (glues, thinners, strippers).

We recorded the presence of trans, trans-muconic acid in urine analyses with exceedances of the biological limit value set at 0.5 mg/g creatinine (Table 7) for some employees in industrial or artisanal shoe companies. In contrast, the inventory of the handled products in the processes did not show the presence of benzene or unleaded gasoline. So, this is due either to the contamination of the used solvents by impurities or an environmental contamination by car exhausts (unleaded gasoline 95) especially since the majority of the employees in these shoe companies use twowheeled vehicles (bicycle or motorcycle).

On the other hand, the analyses of some samples of the products that are handled in the manufacturing of shoes are highly recommended. Furthermore, it also recommended to start an environmental study to check the air quality in the major thoroughfares in Sfax, a city known for its pollution, and to make urine sampling in order to explore the benzene metabolite for people who are exposed to car exhaust (such as traffic wardens, auto mechanics) and unexposed ones.

### 5. Conclusion

GC and HPLC methods have been adjusted, optimized, and effectively used for the determination of OS and their metabolites in airborne and urine samples of solvent manipulators. The exploitation of these indicators had necessitated the use of new techniques for occupational surveillance for the first time in the region. Thus, a process of occupational risk assessment via a biotoxicological and airborne monitoring for solvent exposures is now set.

This study allowed us to provide information on chronic exposure to solvents in the shoe industry and to establish an initial observation on solvent exposure profiles Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry DOI: http://dx.doi.org/10.5772/intechopen.86295

in this sector. However, we know that exposure to solvents is not constant over time and varies according to the task performed and the utilized process. Therefore, the investigation on exposure needs not only the average exposure in comparison with TLV but also to identify the polluting phases in order to determine the short-term exposure.

In the footwear manufacturing sector, following the identification phase of the used solvents and the highlighting of overruns in airborne concentrations of some hazardous products, we plan to focus on the carcinogenic characteristic of certain preparations and especially their potential toxicity for reproduction, since we noted the increase of female presence in the shoe manufacturing sector and some cases of couple sterility.

### Acknowledgements

requirements for environmental protection. These regulatory changes led to changes in the nature of the applied solvents and how to use them [17, 29, 54]. Meanwhile the number of exposed workers is growing in Tunisia. This is confirmed on the international level (in France): the SUMER 2003 survey showed that the number of employees exposed to solvents has increased since 1994 from 12.2 to

Thus, risk assessment studies in various sectors using solvents were started, but the shoe manufacturing sector remained unexplored. This is the case of the study of Poirot and Hubert-Pelle [17] that evaluated exposures to solvents with airborne samples in various industrial activities but not in the manufacture of glue.

If these airborne sampling and biotoxicological analyses were made for the first time in the sector of footwear manufacturing in Sfax, they included a sample of companies from the three manufacturing processes (industrial, semi-industrial, and artisanal); this was preceded by a preliminary risk assessment along with job tasks examinations and an inventory of the handled products [5, 6]. This risk assessment could be improved due to the experience we have gained and with the best knowl-

The results of airborne sampling have confirmed that the existing gaps between the different shoe companies and different workstations were generally those that

All the conducted sampling in the companies indicates that employees' exposure

We recorded the presence of trans, trans-muconic acid in urine analyses with exceedances of the biological limit value set at 0.5 mg/g creatinine (Table 7) for some employees in industrial or artisanal shoe companies. In contrast, the inventory of the handled products in the processes did not show the presence of benzene or unleaded gasoline. So, this is due either to the contamination of the used solvents by impurities or an environmental contamination by car exhausts (unleaded gasoline 95) especially since the majority of the employees in these shoe companies use two-

On the other hand, the analyses of some samples of the products that are handled in the manufacturing of shoes are highly recommended. Furthermore, it also recommended to start an environmental study to check the air quality in the major thoroughfares in Sfax, a city known for its pollution, and to make urine sampling in order to explore the benzene metabolite for people who are exposed to

car exhaust (such as traffic wardens, auto mechanics) and unexposed ones.

GC and HPLC methods have been adjusted, optimized, and effectively used for the determination of OS and their metabolites in airborne and urine samples of solvent manipulators. The exploitation of these indicators had necessitated the use of new techniques for occupational surveillance for the first time in the region. Thus, a process of occupational risk assessment via a biotoxicological and airborne

This study allowed us to provide information on chronic exposure to solvents in the shoe industry and to establish an initial observation on solvent exposure profiles

to organic solvents is quite variable depending on the performed job task. The hippuric acid was highlighted in the urines of some employees with exceedances of the limit value; however, the TLV of toluene has not been exceeded in the companies. This could be explained by a dermal exposure, especially since we have not recorded the use of gloves by workers when they handle preparations used

14.7% mainly in the chemical industry [2].

Standards, Methods and Solutions of Metrology

edge of the sector and the risk prioritization in it.

in shoe manufacturing (glues, thinners, strippers).

wheeled vehicles (bicycle or motorcycle).

monitoring for solvent exposures is now set.

5. Conclusion

88

were indirectly estimated by the workstations observations.

The authors thank the University of Sfax for financial support.

### Conflict of interest

Authors have declared that no conflict of interest exists.

## Author details

Imed Gargouri\*, Fatma Omrane and Moncef Khadhraoui Laboratory "Environmental Engineering and EcoTechnology" LR16ES19, National School of Engineering, University of Sfax, Tunisia

\*Address all correspondence to: imed.gargouri@fmsf.rnu.tn

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## References

[1] Dubeau M. Vapors and gases. In: Occupational Hygiene. 4th ed. Quebec, Canada: Griffen Inc Clay; 1985. pp. 415-523. ISBN: 2-920210-34-3

[2] Testud F, Lambert-Chhum R, Bellemin B, Descotes J. Exposition toxique professionnelle chez la femme enceinte-1 re partie: Principes de l'évaluation du risque individuel. Journal de Gynécologie Obstétrique et Biologie de la Reproduction. 2001;30: 776-779

[3] Wilson MP, Hammond SK, Nicas M, Hubbard AE. Worker exposure to volatile organic compounds in the vehicle repair industry. Journal of Occupational and Environmental Hygiene. 2007;4:301-310

[4] Dor F, Bonvallot N. Hazard identification: A step in the evaluation of health risks deepen. Environment, Health and Risk. 2005;6:279-287

[5] Gonzalez M, Velten M, Cantineau A. Solvent exposure assessment in an epidemiological study of 249 employees. Archives des Maladies Professionnelles de Médecine du Travail. 1999;60: 432-434

[6] INERIS (Institute National Industrial Environment and Risks). Health Risk Assessment Guide. INERIS; 2003. 152p. Available from: http://chimie.ineris.fr/f r/lespdf/guide\_ERS.pdf [Accessed: October 17, 2008]

[7] JORT. Law No. 94-28 of 21 February 1994 on damage compensation scheme for industrial accidents and occupational diseases. JORT 1994;15: 308-318

[8] JORT. Law No. 95-56 of 28 June 1995 on the compensation scheme for damages of occupational accidents and occupational diseases in the public sector. JORT 1995;53:1419-1424

[9] NIOSH Manual of Analytical Methods (NMAM), Hrsg. Volatile Organic Compounds, C1 to C10, Canister Method. Available from: https://www.cdc.gov/niosh/nmam/pdf/ 3900.pdf

2019. ISBN: 978-1-78985-161-8 978-1-

DOI: http://dx.doi.org/10.5772/intechopen.86295

[25] IRSST (Robert-Sauvé Research Institute in Occupational Health and Safety)—Operations Directorate. Sampling Guide for Air Contaminants in the Workplace. 8th ed. IRSST, Canada; 2005. T-06: 191p. Available from: www.irsst.qc.ca [Accessed: August 15,

[26] IRSST. Record Substances Sampling Guide of Air Contaminants in the Workplace. Available from: www.irsst. qc.ca/fr/\_listersst.html [Accessed:

[27] SKC Inc. Air Sample Pumps, Calibrators & Accessories. Sorbent Sample Tubes and Media Collection. Available from: http://www.skcinc.com/

[28] Journal official. Decree No. 2007– 1539 of 26 October 2007 setting binding occupational exposure limit values for certain chemicals and amending the Labor Code (Second Part: Decrees in Council of State). JORF, 28 October

[29] JOUE. Directive 2006/15/EC of 7 February 2006 establishing a second list of indicative lists occupational exposure under Directive 98/24/EC of the Council and amending Directives 91/322/EC and 2000/39/EC. OJEU 9.2.2006:

[Accessed: March 15, 2006]

2007: Text 13 of 52 (NOR:

[30] Pillière FF. Conso Biotox: Biotoxicologique Guide for Doctors. INRS (France) in September 2007, ED 791: 252p. Available from: www.inrs.fr [Accessed: September 15, 2007]

[31] Triplet J. Occupational exposure limits to hazardous substances. ACGIH values (USA) and the MAK commission (Germany). ND 2114-176-99. Notebook

[32] Truchon G. Biomonitoring Guide: Collecting and Interpreting Results.

Notes. 1999;176:59-90

TST0760893D)

L36-L39 (FR)

2006]

Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry

March 20, 2006]

[17] Poirot P, Hubert G. Pelle exposure profiles to solvents and compared to the values short-term limits. ND 2235-200- 05. Notebook Notes. 2005;200:83-93

[18] French Society of Occupational Medicine. Medical surveillance of employees exposed to toxic substances for fetal development. Archives des Maladies Professionnelles et de l'Environnement. 2005;66:165-176

[19] Hertsenberg S, Brouwer D, Lurvink M, Rubingh C, Rijnders E, Tielemans E.

exposure to solvents among shoe repair men. The Annals of Occupational

[20] Cocco P, Tocco MG, Ibba A, Scano L, Ennas MG, Plant C, et al. Trans, trans-muconic acid excretion in relation to environmental exposure to benzene. International Archives of Occupational and Environmental Health. 2003;76:

[21] Armstrong TW, Caldwell DJ, Verma DK. A proposed methodology for setting

occupational exposure limits for hydrocarbon solvents. Journal of Occupational and Environmental

Hygiene. 2005;2:600-607

[22] Mckee HR, Medeiros AM, Daughtrey WC. A proposed

methodology for setting occupational exposure limits for hydrocarbon solvents. Journal of Occupational and Environmental Hygiene. 2005;2:524-542

[23] Hervé-Bazin B. The evaluation guide of exposure to toxic risk in sampling workplace atmosphere. ND 1730-135-89. Notebook Notes. 1989;135:

[24] INRS. Database "Metropol". Available from: www.inrs.f [Accessed:

Quantitative self-assessment of

Hygiene. 2007;51:45-51

456-460

265-288

91

March 20, 2006]

78985-162-5

[10] Huard M. Analytical Method: Determination of Volatile Organic Compounds in the Air by Mass Spectrometry. Available from: https:// www.irsst.qc.ca/media/documents/Pub IRSST/MA-369-EN.pdf

[11] INRS. MétroPol: COV M-338. 2019. Available from: http://www.inrs.fr/pub lications/bdd/metropol/fiche.html?ref INRS=METROPOL\_338

[12] INRS. Benzène (71-43-2)/Acide trans, trans muconique urinaire— Biotox. Available from: http://www.inrs. fr/publications/bdd/biotox/dosage.h tml?refINRS=Dosage\_104

[13] INRS. Toluène (108-88-3)/Acide hippurique urinaire—Biotox. Available from: http://www.inrs.fr/publications/ bdd/biotox/dosage.html?refINRS= Dosage\_99

[14] INRS. n-Hexane (110-54-3)/2,5- Hexanedione totale urinaire—Biotox. Available from: http://www.inrs.fr/pub lications/bdd/biotox/dosage.html?ref INRS=Dosage\_342

[15] Gargouri I, Khadhraoui M, Elleuch B. What are the health risks of occupational exposure to adhesive in the shoe industry? In: Rudawska A, editor. Adhesives—Applications and Properties. London: InTech; 2016. ISBN: 978-953-51-2783-3 978-953-51-2784-0

[16] Gargouri I, Khadhraoui M. Metrology organic solvents in the shoes industry to Sfax city (Tunisia). In: Yilmaz F, editor. Paint and Coatings Industry. London: IntechOpen; Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry DOI: http://dx.doi.org/10.5772/intechopen.86295

2019. ISBN: 978-1-78985-161-8 978-1- 78985-162-5

References

776-779

432-434

308-318

90

October 17, 2008]

for industrial accidents and

[1] Dubeau M. Vapors and gases. In: Occupational Hygiene. 4th ed. Quebec,

Standards, Methods and Solutions of Metrology

[9] NIOSH Manual of Analytical Methods (NMAM), Hrsg. Volatile Organic Compounds, C1 to C10, Canister Method. Available from: https://www.cdc.gov/niosh/nmam/pdf/

[10] Huard M. Analytical Method: Determination of Volatile Organic Compounds in the Air by Mass Spectrometry. Available from: https:// www.irsst.qc.ca/media/documents/Pub

[11] INRS. MétroPol: COV M-338. 2019. Available from: http://www.inrs.fr/pub lications/bdd/metropol/fiche.html?ref

[12] INRS. Benzène (71-43-2)/Acide trans, trans muconique urinaire— Biotox. Available from: http://www.inrs. fr/publications/bdd/biotox/dosage.h

[13] INRS. Toluène (108-88-3)/Acide hippurique urinaire—Biotox. Available from: http://www.inrs.fr/publications/ bdd/biotox/dosage.html?refINRS=

[14] INRS. n-Hexane (110-54-3)/2,5- Hexanedione totale urinaire—Biotox. Available from: http://www.inrs.fr/pub lications/bdd/biotox/dosage.html?ref

[15] Gargouri I, Khadhraoui M, Elleuch

occupational exposure to adhesive in the shoe industry? In: Rudawska A, editor.

Properties. London: InTech; 2016. ISBN: 978-953-51-2783-3 978-953-51-2784-0

Metrology organic solvents in the shoes industry to Sfax city (Tunisia). In: Yilmaz F, editor. Paint and

Coatings Industry. London: IntechOpen;

B. What are the health risks of

Adhesives—Applications and

[16] Gargouri I, Khadhraoui M.

IRSST/MA-369-EN.pdf

INRS=METROPOL\_338

tml?refINRS=Dosage\_104

Dosage\_99

INRS=Dosage\_342

3900.pdf

Canada: Griffen Inc Clay; 1985. pp. 415-523. ISBN: 2-920210-34-3

[2] Testud F, Lambert-Chhum R, Bellemin B, Descotes J. Exposition toxique professionnelle chez la femme enceinte-1 re partie: Principes de l'évaluation du risque individuel. Journal de Gynécologie Obstétrique et Biologie de la Reproduction. 2001;30:

[3] Wilson MP, Hammond SK, Nicas M, Hubbard AE. Worker exposure to volatile organic compounds in the vehicle repair industry. Journal of Occupational and Environmental

Hygiene. 2007;4:301-310

[4] Dor F, Bonvallot N. Hazard

identification: A step in the evaluation of health risks deepen. Environment, Health and Risk. 2005;6:279-287

[5] Gonzalez M, Velten M, Cantineau A. Solvent exposure assessment in an epidemiological study of 249 employees. Archives des Maladies Professionnelles de Médecine du Travail. 1999;60:

[6] INERIS (Institute National Industrial Environment and Risks). Health Risk Assessment Guide. INERIS; 2003. 152p. Available from: http://chimie.ineris.fr/f r/lespdf/guide\_ERS.pdf [Accessed:

[7] JORT. Law No. 94-28 of 21 February 1994 on damage compensation scheme

occupational diseases. JORT 1994;15:

on the compensation scheme for damages of occupational accidents and occupational diseases in the public sector. JORT 1995;53:1419-1424

[8] JORT. Law No. 95-56 of 28 June 1995

[17] Poirot P, Hubert G. Pelle exposure profiles to solvents and compared to the values short-term limits. ND 2235-200- 05. Notebook Notes. 2005;200:83-93

[18] French Society of Occupational Medicine. Medical surveillance of employees exposed to toxic substances for fetal development. Archives des Maladies Professionnelles et de l'Environnement. 2005;66:165-176

[19] Hertsenberg S, Brouwer D, Lurvink M, Rubingh C, Rijnders E, Tielemans E. Quantitative self-assessment of exposure to solvents among shoe repair men. The Annals of Occupational Hygiene. 2007;51:45-51

[20] Cocco P, Tocco MG, Ibba A, Scano L, Ennas MG, Plant C, et al. Trans, trans-muconic acid excretion in relation to environmental exposure to benzene. International Archives of Occupational and Environmental Health. 2003;76: 456-460

[21] Armstrong TW, Caldwell DJ, Verma DK. A proposed methodology for setting occupational exposure limits for hydrocarbon solvents. Journal of Occupational and Environmental Hygiene. 2005;2:600-607

[22] Mckee HR, Medeiros AM, Daughtrey WC. A proposed methodology for setting occupational exposure limits for hydrocarbon solvents. Journal of Occupational and Environmental Hygiene. 2005;2:524-542

[23] Hervé-Bazin B. The evaluation guide of exposure to toxic risk in sampling workplace atmosphere. ND 1730-135-89. Notebook Notes. 1989;135: 265-288

[24] INRS. Database "Metropol". Available from: www.inrs.f [Accessed: March 20, 2006]

[25] IRSST (Robert-Sauvé Research Institute in Occupational Health and Safety)—Operations Directorate. Sampling Guide for Air Contaminants in the Workplace. 8th ed. IRSST, Canada; 2005. T-06: 191p. Available from: www.irsst.qc.ca [Accessed: August 15, 2006]

[26] IRSST. Record Substances Sampling Guide of Air Contaminants in the Workplace. Available from: www.irsst. qc.ca/fr/\_listersst.html [Accessed: March 20, 2006]

[27] SKC Inc. Air Sample Pumps, Calibrators & Accessories. Sorbent Sample Tubes and Media Collection. Available from: http://www.skcinc.com/ [Accessed: March 15, 2006]

[28] Journal official. Decree No. 2007– 1539 of 26 October 2007 setting binding occupational exposure limit values for certain chemicals and amending the Labor Code (Second Part: Decrees in Council of State). JORF, 28 October 2007: Text 13 of 52 (NOR: TST0760893D)

[29] JOUE. Directive 2006/15/EC of 7 February 2006 establishing a second list of indicative lists occupational exposure under Directive 98/24/EC of the Council and amending Directives 91/322/EC and 2000/39/EC. OJEU 9.2.2006: L36-L39 (FR)

[30] Pillière FF. Conso Biotox: Biotoxicologique Guide for Doctors. INRS (France) in September 2007, ED 791: 252p. Available from: www.inrs.fr [Accessed: September 15, 2007]

[31] Triplet J. Occupational exposure limits to hazardous substances. ACGIH values (USA) and the MAK commission (Germany). ND 2114-176-99. Notebook Notes. 1999;176:59-90

[32] Truchon G. Biomonitoring Guide: Collecting and Interpreting Results.

6th ed. Canada: IRSST; 2004. T-03: 92p. Available from: www.irsst.qc.ca [Accessed: May 19, 2005]

[33] William W, Ernest L, Christiani DC. Biomarker research in occupational health. Journal of Occupational and Environmental Medicine. 2005;47: 145-153

[34] Grandjean P, Budtz-Jørgensen E. Total imprecision of exposure biomarkers: Implication for calculating exposure limits. American Journal of Industrial Medicine. 2007;50:712-719

[35] Schneider O, Brondeau MT. Biological exposure indices. ND 2245-202-06. Notebook Notes. 2006; 202:49-65

[36] Schulz C, Angerer J, Ewers U, Kolossa-Gehring M. The german human biomonitoring commission. International Journal of Hygiene and Environmental Health. 2007;210: 373-382

[37] Boeckelmann I, Pfister EA. Influence of occupational exposure to organic solvent mixtures in contrast sensitivity in printers. Journal of Occupational and Environmental Medicine. 2003;45:25-33

[38] Delinsky AD, Bruckner JV, Bartlett MG. A review of analytical methods for the determination of trichlorethylene and its major metabolites chloral hydrate, trichloroacetic acid and dichloroacetic acid. Biomedical Chromatography. 2005;19:617-639

[39] Eller PM, Cassinelli ME. NIOSH Manual of Analytical Methods (NMAM). 4th ed. USA: CDC; 1994. Available from: www.cdc.gov/niosh/ nmam [Accessed: August 15, 2006]

[40] Kawai T, Miyama Y, Horiguchi S, Sakamoto K, Zhang ZW, Higashikawa K, et al. Possible metabolic interaction entre hexane solvents other co-exposed at sub-occupational exposure limit levels. International Archives of Occupational and Environmental Health. 2000;73:449-456

monitoring of occupational exposure to cyclohexane by urinary 1,2- and 1,4 cyclohexanediol determination. International Archives of Occupational and Environmental Health. 1999;72:

DOI: http://dx.doi.org/10.5772/intechopen.86295

Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry

[54] JORF. Decree No. 2008–602 of 25 June 2008 on recycling and waste from the textile apparel products, new house shoes or clothes for households. JORF No 149 of 27 June 2008 (NOR:

DEVP0772293D)

[48] Takeuchi A, Kawai T, Zhang ZW, Miyama Y, Sakamoto K, Higashikawa K, et al. Toluene, xylenes and xylene isomers in urine as biological indicators of low-level exposure to each solvent: A comparative study. International Archives of Occupational and

Environmental Health. 2002;75:387-393

[49] Takeuchi A, Kawai T, Zhang ZW, Miyama Y, Sakamoto K, Higashikawa K,

Environmental Health. 2004;77:264-270

[50] Courtois B. Occupational exposure limits to chemicals in France. National Institute for Research and Security [INRS] (France) in December 2007, ED

[51] Poirot P, Subra I, Baudin V, Hery M, Chouanière D, Vincent R. Determining medium-term exposure profile of house painters. Notebook Notes. 2000;179:

[52] Kawai T, Yasugi T, Mizunuma K, Horiguchi SI, Ikeda M. Comparative evaluation of blood and urine analysis as

[53] Tkaukiainen A, Vehmas T, Rantata

tool for biological monitoring of n-hexane and toluene. International Archives of Occupational and Environmental Health. 1993;65:

K, Numinen M, Martikainen R, Taskinen H. Results of laboratory tests common in solvent-exposed workers. International Archives of Occupational and Environmental Health. 2004;77:

et al. Comparison of n-hexane unchanged in alveolar air and 2,5 hexanedione in urine for the biological monitoring of n-hexane exposure in human volonteers. International Archives of Occupational and

115-120

984: 19p

S123-S1S6

39-46

93

5-13. ND2125-179-00

[41] Pergiago JF, Cardona A, Marhuenda D, Roel J, Villanueva M, Marti J, et al. Biological monitoring of occupational exposure to n-hexane by exhaled air analysis and urinalysis. International Archives of Occupational and Environmental Health. 1993;65:275-278

[42] Soulage C, Perrin D, Berenguer P, Pequignot JM. Sub-chronic exposure to toluene at 40 ppm alters the monoamine biosynthesis rate in discrete brain areas. Toxicology. 2004;196:21-30

[43] Calafat AM, Kklenyik Z, Caudill SP, Ashley DL. Urinary levels of trichloacetic acid, a disinfection byproduct in chlorinated drinking water, in a human reference population. Environmental Health Perspectives. 2003;111:151-154

[44] Johns DO, Dills RL, Morgan MS. Evaluation of dynamic headspace with gas chromatography/mass spectrometry for the determination of 1,1,1 trichloroethane, trichloroethanol, and trichloroacetic acid in biological samples. Journal of Chromatography B. 2005;817:255-261

[45] Lof A, Hjelm EW, Colmsjo A, Lundmark BO, Norström A, Sato A. Toxicokinetics of toluene and urinary excretion of hippuric acid afterhuman exposure to toluene. British Journal of Industrial Medicine. 1993;50: 55-59

[46] O'Donnell GE, Juska A, Geyer R, Faiz M, Stalder S. Analysis of trichloroacetic acid in the urine of workers occupationally exposed to trichlorethylene by capillary gas chromatography. Journal of Chromatography A. 1995;709:313-317

[47] Perico A, Cassinelli C, Brugnone F, Bavazzano P, Perbellini L. Biological

Biotoxicological Monitoring of Organic Solvents in the Tunisian Footwear Industry DOI: http://dx.doi.org/10.5772/intechopen.86295

monitoring of occupational exposure to cyclohexane by urinary 1,2- and 1,4 cyclohexanediol determination. International Archives of Occupational and Environmental Health. 1999;72: 115-120

6th ed. Canada: IRSST; 2004. T-03: 92p.

Standards, Methods and Solutions of Metrology

at sub-occupational exposure limit levels. International Archives of Occupational and Environmental

[41] Pergiago JF, Cardona A, Marhuenda D, Roel J, Villanueva M, Marti J, et al. Biological monitoring of occupational exposure to n-hexane by exhaled air analysis and urinalysis. International Archives of Occupational and

Environmental Health. 1993;65:275-278

[42] Soulage C, Perrin D, Berenguer P, Pequignot JM. Sub-chronic exposure to toluene at 40 ppm alters the monoamine biosynthesis rate in discrete brain areas.

[43] Calafat AM, Kklenyik Z, Caudill SP,

[44] Johns DO, Dills RL, Morgan MS. Evaluation of dynamic headspace with gas chromatography/mass spectrometry

trichloroethane, trichloroethanol, and trichloroacetic acid in biological

samples. Journal of Chromatography B.

urinary excretion of hippuric acid afterhuman exposure to toluene. British Journal of Industrial Medicine. 1993;50:

[46] O'Donnell GE, Juska A, Geyer R,

Chromatography A. 1995;709:313-317

[47] Perico A, Cassinelli C, Brugnone F, Bavazzano P, Perbellini L. Biological

Faiz M, Stalder S. Analysis of trichloroacetic acid in the urine of workers occupationally exposed to trichlorethylene by capillary gas chromatography. Journal of

[45] Lof A, Hjelm EW, Colmsjo A, Lundmark BO, Norström A, Sato A. Toxicokinetics of toluene and

for the determination of 1,1,1-

Toxicology. 2004;196:21-30

Ashley DL. Urinary levels of trichloacetic acid, a disinfection byproduct in chlorinated drinking water, in a human reference population. Environmental Health Perspectives.

2003;111:151-154

2005;817:255-261

55-59

Health. 2000;73:449-456

[33] William W, Ernest L, Christiani DC. Biomarker research in occupational health. Journal of Occupational and Environmental Medicine. 2005;47:

[34] Grandjean P, Budtz-Jørgensen E. Total imprecision of exposure

biomarkers: Implication for calculating exposure limits. American Journal of Industrial Medicine. 2007;50:712-719

[35] Schneider O, Brondeau MT. Biological exposure indices. ND 2245-202-06. Notebook Notes. 2006;

[36] Schulz C, Angerer J, Ewers U, Kolossa-Gehring M. The german human

International Journal of Hygiene and Environmental Health. 2007;210:

[38] Delinsky AD, Bruckner JV, Bartlett MG. A review of analytical methods for the determination of trichlorethylene and its major metabolites chloral hydrate, trichloroacetic acid and dichloroacetic acid. Biomedical Chromatography. 2005;19:617-639

[39] Eller PM, Cassinelli ME. NIOSH Manual of Analytical Methods (NMAM). 4th ed. USA: CDC; 1994. Available from: www.cdc.gov/niosh/ nmam [Accessed: August 15, 2006]

[40] Kawai T, Miyama Y, Horiguchi S, Sakamoto K, Zhang ZW, Higashikawa K, et al. Possible metabolic interaction entre hexane solvents other co-exposed

biomonitoring commission.

[37] Boeckelmann I, Pfister EA. Influence of occupational exposure to organic solvent mixtures in contrast sensitivity in printers. Journal of Occupational and Environmental

Medicine. 2003;45:25-33

Available from: www.irsst.qc.ca [Accessed: May 19, 2005]

145-153

202:49-65

373-382

92

[48] Takeuchi A, Kawai T, Zhang ZW, Miyama Y, Sakamoto K, Higashikawa K, et al. Toluene, xylenes and xylene isomers in urine as biological indicators of low-level exposure to each solvent: A comparative study. International Archives of Occupational and Environmental Health. 2002;75:387-393

[49] Takeuchi A, Kawai T, Zhang ZW, Miyama Y, Sakamoto K, Higashikawa K, et al. Comparison of n-hexane unchanged in alveolar air and 2,5 hexanedione in urine for the biological monitoring of n-hexane exposure in human volonteers. International Archives of Occupational and Environmental Health. 2004;77:264-270

[50] Courtois B. Occupational exposure limits to chemicals in France. National Institute for Research and Security [INRS] (France) in December 2007, ED 984: 19p

[51] Poirot P, Subra I, Baudin V, Hery M, Chouanière D, Vincent R. Determining medium-term exposure profile of house painters. Notebook Notes. 2000;179: 5-13. ND2125-179-00

[52] Kawai T, Yasugi T, Mizunuma K, Horiguchi SI, Ikeda M. Comparative evaluation of blood and urine analysis as tool for biological monitoring of n-hexane and toluene. International Archives of Occupational and Environmental Health. 1993;65: S123-S1S6

[53] Tkaukiainen A, Vehmas T, Rantata K, Numinen M, Martikainen R, Taskinen H. Results of laboratory tests common in solvent-exposed workers. International Archives of Occupational and Environmental Health. 2004;77: 39-46

[54] JORF. Decree No. 2008–602 of 25 June 2008 on recycling and waste from the textile apparel products, new house shoes or clothes for households. JORF No 149 of 27 June 2008 (NOR: DEVP0772293D)

## *Edited by Luigi Cocco*

The goal of acceptable quality, cost, and time is a decisive challenge in every engineering development process. To be familiar with metrology requires choosing the best combination of techniques, standards, and tools to control a project from advanced simulations to final performance measurements and periodic inspections. This book contains a cluster of chapters from international academic authors who provide a meticulous way to discover the impacts of metrology in both theoretical and application fields. The approach is to discuss the key aspects of a selection of untraditional metrological topics, covering the analysis procedures and set of solutions obtained from experimental studies.

Published in London, UK © 2019 IntechOpen © allanswart / iStock

Standards, Methods and Solutions of Metrology

Standards, Methods and

Solutions of Metrology

*Edited by Luigi Cocco*