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January2008 Vol.45 Issue:      1 Table of Contents
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Cognitive Functions Changes in Egyptian Sewage Networks Workers

Farahat S.A.1, Kishk N.A.2, El-Kholy M.3
Departments of Industrial Medicine & Occupational Diseases1, Neurology2, Cairo University Family Medicine3, Suez Canal University

ABSTRACT

Hydrogen sulfide is a toxic gas about which much has been written. It constitutes one of the most serious chemical hazards to which sewage network workers are exposed to. Objectives: The current work aimed at assessment of cognitive dysfunctions among workers of sewer networks and the relation of these changes, if any, to the level of exposure to the biomarker, urinary thiosulfate. A trial for setting a screening test for cognitive function change. Subjects: The work was conducted among 34 male workers involved in the maintenance of the sewage network and a matched unexposed control group (n= 21). Methods: The participants were subjected to clinical neurological examination, estimation of urinary thiosulfate as hydrogen sulfide exposure biomarker, and assessment of cognitive functions changes by using neurophysiological (simple reaction time, P300 test) and neuropsychological tests (Wechsler Memory Scale) and frontal executive functions. Results: Clinical neurological history revealed significantly higher neurological symptoms (headache, memory defects, lack of concentration) among exposed workers compared to their controls (P< 0.05). Marked elevation of urinary thiosulfate was observed among the exposed workers (P< 0.001) although this elevation was not correlated with the duration of exposure. Exposed workers showed poor performance of most of neuropsychological tests compared to control subjects. Significantly prolonged simple reaction time and delayed P300 latency were found among sewer network workers. Most of exposed workers had significantly lower Mini-Mental State Examination (MMSE) scoring than that of the controls (P<0.001). MMSE was significantly correlated with other neuropsychological tests. Conclusion & Recommendation: Exposure of sewer network workers is associated with significant cognitive dysfunction which can be screened by applying MMSE annually as a screening test of the exposed workers.

(Egypt J. Neurol. Psychiat. Neurosurg., 2008, 45(1): 43-56)

 




 


INTRODUCTION

 

The sewage system is a vast network of underground canals whose network duplicates nearly perfectly the street network. It drains the waste water towards the treatment plants1. This system consists of three typical environments:

·           Small (primary) lines connect buildings to the sewage system. The diameters of these lines vary from 1.2 to 2.0 m. When these lines need to be cured, the sewage workers intervene directly with handheld tools.

·           Secondary and main collectors (canals) regroup the output of the primary lines. These collectors are larger and small sidewalks allow the workers to walk along these canals. The clearing of these canals is done using wagons or boats allowing the regulation of the flow of the wastewater.

·           More or less large sedimentation basins slow down the wastewater flow in order to get rid of the sediments which are extracted by aspiration from the streets1.

 

Sewage workers perform numerous specific tasks, each with its own special hazardous exposure2. Work in sewage system presents constant exposure to noxious gases and vapors as well as explosive substances and infectious agents. A first source of exposure to chemical agents, in particular to sulfur compounds (hydrogen sulfide, mercaptans), carbon monoxide, methane, aldehydes, and organic acids, occurs through the decomposition of urine and feces in either aerobic or anaerobic conditions. These chemicals are notably released in the air during the curing and extraction operations. A second possible source of chemical exposure is when industries dump their waste into the sewage system3.  

Sewer gas refers to the odor associated with sewers, waste treatment plants and septic tanks. It contains hydrogen sulfide (H2S) and reduced sulfur compounds, such as methyl and dimethyl sulfide, ethyl and diethyl sulfide. These organo-sulfur compounds add to the toxicity of the H2S in the sewer gas4.

Exposure to H2S occurs primarily by inhalation but can also occur by ingestion (contaminated food) and skin (water and air). Once taken into the body, it is rapidly distributed to various organs, including the central nervous system, lungs, liver, and muscle. The major metabolic pathway for H2S in the body is the oxidation of sulfide to sulfate, which is excreted in the urine. The major oxidation product of sulfide is thiosulfate, which is then converted to sulfate; the primary location for these reactions is in the liver5. Hydrogen sulfide is a mitochondrial poison. Its action on mitochondria is similar to that of cyanide through inhibition of cytochrome oxidase (iron containing protein). This prevents the utilization of oxygen with an uncoupling of oxidative phosphorylation. In addition, H2S binds to hemoglobin in red blood cells interfering with oxygen transport6.

Although adverse effects of acute exposure to H2S are well documented, long term effects of occupational exposure to low levels of the gas are not. Some studies demonstrated fatigue, poor memory, dizziness, and irritability in workers chronically exposed to H2S. However, it is not known if these effects are the result of chronic exposure or due to reoccurring acute exposures7.

 

Aim of the work:

§   Assessment of cognitive functions changes among workers of sewage networks and the relation of these changes, if any, to the level of exposure biomarker, thiosulfate.

§   A trial for setting a screening test for cognitive function changes.

SUBJECTS AND METHODS

 

Subjects:

This study was carried out among 34 littered male workers involved in maintenance of the sewage network of the regions El Manial, Misr el Kadema, and Kasr El- Aini hospital. The workers were responsible for inspection of lines in order to detect any perturbation of the waste water flow and possible defaults (for example, cracks, leaks) of the duct, the curing of the waste water lines and the extraction of the sediments. Their frequency of exposure was about 3-4 times/week

The control subjects comprised 21 male personnel who are not exposed to sewage and with similar, residence, educational and socioeconomic status as the exposed sewage workers.

 

Methods:

The study involved 2 main parts:

I )            Environmental study

§   First, it should be noted that at the time of performing the environmental study, there was no noticed obstructions in any of sewer networks in the previously mentioned regions.

§   Measurement of the ambient H2S was done in 5 areas; at the edge of entry openings of 2 sewers in El Manial and Kasr El-Aini hospital, around the openings of the 2 sewers within a circle of a circumference of 0.5-1 m, and a control area.

§   Collection of H2S gas was accomplished by utilizing the absorption method. The contaminated air was drawn using a calibrated vacuum pump, dry gas meter, and a glass bubbler containing 50 ml of the reagent (2 CdSO4. 8 H2O and sodium hydroxide). The sampling pump was calibrated to draw 1l/ min and air was sampled for 2 hours. This procedure was repeated 3 times at each place of sampling.

§   The methylene blue method was used for H2S measurement. Collection in cadmium sulfate (CdSO4) actually is the method of choice due its high sensitivity. The intensity of methylene blue color was measured at 670 nm. Then the standard curve and the volume of air sample were used to calculate the concentration of H2S 8.

 

II)            Biological study

Each subject of the study was subjected to:

1.      Thorough medical history taking (including occupational history) and meticulous neurological examination.

According to the taken history and clinical examination, some exclusion criteria were applied.

Exclusion criteria:

1.   History of unconsciousness at work (acute intoxication)

2.   Evidence of hypertension or diabetes.

3.   Subjects with previous history of neurological disorders

4.   Patients with depression or other psychiatric disorders.

 

After implementing exclusion criteria, 7 workers out of the thirty four but none from the control group, were excluded from the study, 3 of the workers having advanced liver diseases, and 4 for having history of unconsciousness during their work. The rest of subjects (exposed and control) were subjected to:

 

2.      Monitoring of the exposure to H2S using estimation of thiosulfate in the urine

Procedure

Thiosulfate is determined in urine after removal of interfering compounds including endogenous thiocyanate by ion exchange. First, thiosulfate is converted to thiocyanate in the presence of cyanide and cupric ions, then, the formed thiocynate is concentrated and diluted with acid solution of ferric ion. Ferric thiocyanate using caloremetry at 500 nm wave length9.

 3.     Monitoring of the H2S effect using neurobehavioral tests

a)   Neurophysiological Tests:

Long latency evoked potentials (P300):

Event related potentials (ERP) represent the neural activity generated during cognitive process.24 P300 recorded in a sound attenuated room (Oddball paradigm), multimodality evoked potentials machine (Micromed) was used to record the responses. Disc electrodes were placed over the scalp after properly cleaning the skin with an adhesive gel. The active electrode was applied at Cz of the 10-20 international system of electrode placement. Both the reference electrode and the ground were applied to ear lobule and FPZ respectively. The electrodes impedance was kept below 5 KOhms. The hearing threshold for each subject was determined. A total of 200 auditory stimuli (bursts) were presented to the ears through earphones with intensity of 60 db above the hearing threshold. 70% of tones were 1000 Hz in frequency (background tones) whereas the remaining 30% were 2000 Hz (target tones). The subject was instructed to press on a button connected to the apparatus as quickly as possible whenever hearing the target tones. These tones were presented randomly intermixed at a rate of 0.5/second. The tones were applied so as no 2 target tones came in succession.

The wave P300 was defined as the most positive point of the average waveform to the target tones after 250 msec and before 600 msec. To verify reproducibility of the response, the procedure was repeated at least once. The responses were displayed on a screen and could be printed out. For each subject, P300 latency, P300 amplitude and Reaction Time were obtained to detect any significant abnormality.

P300 latency was considered abnormal if it was above +2 standard deviations (SD) of the mean latency measured in age matched controls10.

b)   Neuropsychological Assessment:

A.  Wechsler Memory Scale-revised (WMS-R)11:

                         It consists of 13 subtests. In this work, we selected the subtests which assess the visual memory and the logical memory:

1. Visual memory subtests:

                                                a. Figural memory:

    The maximum score is 10.

b. Visual Paired Associates I:

    Maximum score is 18.

c. Visual Reproduction I:

    Maximum score is 4.

The previous 3 tests assess the non verbal working memory.

d. Digit Span:

This test measures attention process and working memory

i)    Digit forward (Normal: 6±1, Borderline or impaired: 4, Defective: 3)

ii)   Digit backward (Normal: 5±1, Borderline or impaired: 3, Defective: 2)

2.                Logical Memory Subtest:

The total scoring of 50 and a patient who scores <25 is considered to have learning and working memory difficulties.

B.  Frontal executive functions: (Initiation, Response shifting and Set shifting)

1. Controlled Oral Word Associa-

     tion Test (COWA)12.  

It assesses the patient’s ability to generate responses by having them produced as many words as possible in one minute related to certain category, beginning with the names of foods, then names of animals.

Patients who score <15 words on the average scores of foods and animals names were showed to have impairment on this task.

2. Design fluency

The maximum score is 4

3. Alternating sequences

Score 1 or 0.

4. Trail Making Test

Score 1 or 0.

The previous tests assess the response inhibition and set shifting

C.  Mini-Mental State Examination (MMSE)13.

MMSE is used to assess:

§  Orientation to time and place.

§  Instantaneous recall.

§  Short term memory.

§  Serial subtractions or reverse spelling.

§  Constructional capacities (copying a design).

§  Use of language.

 

The total score is 30 for educated persons. The score 27 indicate mild cognitive impairment.

The aim of the MMSE in this study was to asses the possibility of using the test for screening of cognitive dysfunction as a result of H2S exposure.

 

Statistical analysis:

Results were evaluated for each group. Data were compared using Student t test. Results of neurological symptoms and trail making and alternating sequence tests were expressed as frequency distribution using Chi2 test. Pearson correlation test was used to correlate between different variables among the exposed groups. The statistical significance was defined as P-value <0.05. Computer based Statistical Package for Social Sciences (SPSS) for windows 9.1 program was used.

 

RESULTS

 

This work was conducted among 34 male sewer network workers involved in maintenance of the sewage network of the regions El Manial, Misr el Kadema, and Kasr El-Aini Hospital. They are exposed regularly to H2S gas. The control group included 21 male subjects who were not exposed to H2S. Both exposed and control groups were matched as regards age as there was no significant difference between the mean ±SD of the age of both groups (47.3±8.2 & 43.0±8.0, respectively, P>0.05). The Smoking index of both groups was matched (9.3±7.0 & 9.9±5.9, respectively, p>0.05). The mean±SD of duration of work among the exposed group is 17.9±6.7 years.

Multiple air samples were collected at the edge of the sewer and around it as well as from a control area. As shown in table (1), the mean values of air samples were found to be below the Permissible Exposure Limit (PEL) established by the Occupational Safety and Health Administration OSHA and the American Conference of Governmental Industrial Hygienists (ACGIH) (14 mg/m3 or 10 ppm (part per million)). One of the individual readings was exceeding this limit (14.6 mg/m3 / 10.5 ppm).

Marked increase of the frequency of neurological symptoms namely (headache, lack of concentration and memory defects) was detected among exposed workers compared to their controls (Table 2) (P<0.05).

The sewer workers showed poor performance of neuropsychological tests as was detected from the lower mean values of (Wechsler Memory Scale-revised) subtests compared to controls, especially visual reproduction (2.5±0.9 versus 4.5±0.6) digit backwards (3.09±0.91 versus 8.05±1.09) and digit forwards (4.55±0.79 versus 5.86±1.21) tests (P<0.001). Logical memory and figural memory which were insignificantly different between exposed and control groups although they were lower among the exposed subjects. Qualitative frontal executive function tests (COWA and design fluency) of the exposed workers were significantly lower than the controls. Similarly, the frequency of other qualitative frontal executive function tests (trail making and alternative sequences) were significantly higher among the exposed workers (P<0.001) (Table 3).

As regards neurophysiological tests (simple reaction time, P300 latency & amplitude), results revealed statistically significant (P<0.001) prolongation of simple reaction time, and P300 latency among the exposed workers in msec (377.18±42.47 & 487.33±45.23, respectively) versus (315.14±29.83 & 301.56±17.61) in the controls (Table 4). P300 amplitude was insignificantly lower among the exposed workers than in control subjects.

On estimation of urinary thiosulfate as an index of H2S exposure, there was marked increase of its concentration among the exposed workers (50.62±8.96) compared to their controls (25.13±5.07) (P<0.001) (Table 5).

MMSE test was significantly lower among the exposed workers (P<0.001) (Table 5)

Correlation of urinary thiosulfate versus duration of work, neuropsychological subtests and neurophysiological subtests, revealed insignificant results (P>0.05) (Table 6).

There was significant negative correlation between digit backwards test with prolonged P300 latency (r= -0.378 & P<0.05) (Fig. 1a) and between digit forwards test with prolonged simple reaction time (r= -0.398 & P<0.05) (Fig. 1b).

There were insignificant negative correlation between MMSE score and P300 latency (m sec) (r=0.210, P>0.05) (Fig. 2). Significant positive correlation was revealed between MMSE score versus both digit backwards (r=0.480 & P<0.05, Fig. 3a) and design fluency tests (r= 0.635& P<0.001, Fig. 3b).


 

Table 1. Mean±SD of the air concentrations of hydrogen sulfide gas (in ppm & mg/m3) in different air samples collected around the sewer openings and from a control area.

 

 

1st reading

2nd reading

3rd reading

Mean± SD

At the 1st opening

12.2 mg/m3 (8.8ppm)

13.4 mg/m3

9.6 ppm

14 mg/m3

10 ppm

13.2 mg/m3

9.4 ppm

At the 2nd opening

13.9 mg/m3

(10 ppm)

11.3 mg/m3

8.1 ppm

14.6 mg/m3*

10.5 ppm*

13.2 mg/m3

9.5 ppm

Around the 1st opening

8.4 mg/m3

6 ppm

7.5 mg/m3

5 ppm

9.2 mg/m3

6.6 ppm

8.3 mg/m3

5.8

Around the 2nd opening

Nil

8.6 mg/m3

6.2 ppm

7.9 mg/m3

5.6 ppm

5.5 mg/m3

3.9 ppm

Control area

Nil

Nil

Nil

Nil

* Hydrogen sulfide air concentration exceeded the PEL established by the OSHA (14 mg/m3 or 10 ppm time weighted average TWA).

Table 2. Frequency distribution of neurological symptoms among both exposed and control groups as detected from the clinical history.

 

 

Exposed (n=27)

Control (n=21)

c2

p-value

No.

%

No.

%

Headache

15

55.5

2

9.5

8.173

<0.05*

Memory defects

15

55.5

1

4.7

10.709

<0.05*

Lack of concentration

12

44.4

2

9.5

5.174

<0.05*

* Statistically significant P<0.05

 

Table 3. Mean±SD of the results of neuropsychological tests (Wechsler Memory Scale-revised (WMS-R) subtests & Frontal executive functions tests) among both exposed and control subjects.

 

 

Exposed (n=27)

Control (n=21)

 

t-value

 

p-value

§ WMS-R

- Figural memory

- Visual paired

- Visual reproduction

- Digit forward

- Digit backward

- Logical memory

 

8.91±1.38

9.00±1.37

2.55±0.90

4.55±0.79

3.09±0.913

29.91±4.00

 

8.77±1.23

10.09±2.33

4.50±0.60

5.86±1.21

8.05±1.09

31.95±4.19

 

0.375

2.189

8.908

4.893

18.229

1.822

 

NS

<0.05

<0.001

<0.001

<0.001

NS

Frontal executive functions

- COWA

- Design fluency

 

11.82±2.56

2.45±1.39

 

14.14±3.18

3.68±0.57

 

2.987

3.909

 

<0.05

<0.001

Abnormal performance

No.

%

No.

%

c2

p-value

Trail making

15

55.5

0

0

13.750

<0.001

Alternative sequence

6

55.5

0

0

4.490

<0.001

 

Table 4. Mean±SD of the results of neurophysiological tests (simple reaction time, P300 test latency & amplitude).

 

 

Exposed (n=27)

Control (n=21)

t-value

p-value

Simple reaction time (m sec)

377.18±42.47

315.14±29.83

5.938

<0.001

P300 latency (m sec)

487.33±45.23

301.56±17.61

18.317

<0.001

P300 amplitude (µv)

13.410±6.53

16.05±4.74

1.627

NS

 

Table 5. Mean±SD of urinary thiosulfate (μmol/mg creatinine) as exposure biomarker and Mini Mental State Examination test (MMSE) as effect biomarker among both exposed and control groups.

 

 

Exposed

(n=27)

Control

(n=21)

t-value

p-value

Urinary thiosulfate (μmol/mg creatinine)

50.62±8.96

25.13±5.07

12.095

<0.001*

MMSE test

27.09±1.01

30±0.0

9.466

<0.001*

* Highly significant

Table 6: Correlation coefficient (r) between urinary thiosulfate (μmol/mg creatinine) versus duration of work and the results of different neurophysiological and neuropsychological tests in the exposed workers

 

 

Urinary thiosulfate

p-value

Duration of work

r=0.144

NS

Neurophysiological tests

- Simple reaction time

- P300 latency

 

r=0.231

r=0.069

 

NS

NS

Neuropsychological tests

- Digit forward

- Digit backward

- Logical memory

- Design fluency

 

r=0.184

r=0.229

r=0.040

r=0.074

 

NS

NS

NS

NS

 

 

 

Fig. (1a): Significant negative correlation between digit backwards test with

prolonged P300 latency (r= -0.378 & P<0.05)

 

 

Fig. (1b): Significant negative correlation between digit backwards test with

prolonged P300 latency (r= -0.378 & P<0.05)

 

Fig. (2): Insignificant negative correlation between MMSE test score and

P300 latency (m sec) (r=0.210 & P>0.05).

 

 

Fig. (3a): Positive significant correlation coefficient between both MMSE test score

versus digit backwards in the exposed workers (r= 0.480 & P<0.05).

 

 

Fig. (3b): Positive significant correlation coefficient between both MMSE test score

versus design fluency in the exposed workers (r= 0.635 & P<0.001).

 

 

DISCUSSION

 

Sewer network workers are exposed to multitudes of chemical and biological hazards. One of these serious chemical hazards is the occasional exposure to high concentrations of H2S gas in the confined space of sewer pipes14. Death occurring after single exposures to high concentrations of H2S appears to be the result of respiratory failure or arrest, with most cases initially presenting with respiratory insufficiency, non-cardiogenic pulmonary edema, coma, and cyanosis15.  

However, exposure to H2S among sewer workers is not limited to fatal concentrations, but low dose exposure is encountered during their routine work of inspection and maintenance of the sewer networks apart of the time of obstruction. Hence, the environmental assessment of H2S gas concentrations in the air "at the edge of sewer entry opening and in the area around the openings", was performed in this study as an index of the actual occupational exposure to H2S gas among sewer workers during their routine work, taking into consideration the occasional exposure of sewage workers to higher levels of H2S gas during the periods of sewer obstruction. The mean values of H2S air concentrations exceeded the PEL stated by the OSHA in one individual reading (10.5 ppm). This means that, sewer workers are at risk of exposure to H2S gas during their routine work to levels that may exceed the recommended permissible levels, especially inside the sewer pipes which will be higher than that at the edge of the openings or

around it, thus carrying the risk of long term consequences of exposure to H2S gas.

OSHA has established 10 ppm to be a PEL for H2S over an 8 hour work shift. The same level was established by The American Conference of Governmental Industrial Hygienists (ACGIH). OSHA has established an acceptable ceiling concentration of 20 ppm for H2S in the workplace with a maximum level of 50 ppm allowed for a maximum of 10 minutes time while Short Term Exposure Limit (STEL) is 15 ppm for any 15 minute period (ATSDR, 1999). On the other hand, NIOSH (1994) has set a recommended exposure limit ceiling value of 10 ppm, for 10 minutes exposure16.

However, in UK, the Working Group on the Assessment of Toxic Chemicals (WATCH) suggested 5 ppm to the occupational exposure limit (OEL) for H2S 3. The recommendation to review the OELs for H2S is because in the mid 1990s a series of human volunteer studies were published that suggested exposures as low as 10 ppm might cause a shift to anaerobic metabolism under conditions of physical exertion. This leads to a concern for adverse physiological effects at what were at the time the existing occupational exposure standard (OES) values for H2S of 10 ppm (8 hour time weighted average (TWA)) and 15 ppm (short term exposure limit (STEL)).

Many studies have documented the neurological effects following single inhalation exposures to high concentrations of H2S. These effects may be permanent or persistent and include visual and memory impairment, reduced motor function, slight tremor, ataxia, psychosis, abnormal learning, retention, and motor function, and slight cerebral atrophy17.   

To the best of our knowledge, very limited number of studies have discussed the neurological consequences following long term exposure to low concentrations of H2S. However, ATSDR (2004), reported that long term exposure to low concentrations of H2S is associated with neuropsychiatry manifestations, including: fatigue, loss of appetite, irritability, impaired memory, altered mood states, headache and dizziness16.   

On investigating the frequency of central nervous system symptoms among the exposed group, a significantly higher percentage was found among the exposed group compared to the controls (P<0.01). These results are greatly supported by a similar study of Thorn et al.18, who reported significantly increased risks for airway symptoms, as well as central nervous system among sewage workers. Also similar symptoms were reported among ex-workers and neighboring residents who were exposed to H2S and other reduced-sulfur compounds emitted from a refinery in concentrations ranged from a low of 8.8 ppm to 10 ppm19.  Additionally, similar results were reported by Legator20 in his studies in two communities exposed to industrial sources of H2S. 

However, surveys and studies of subjective reported symptoms may be susceptible to response enhancement bias (i.e., an increase in reported symptoms resulting from the fact that respondents are aware of, and sensitized to, the fact that they are exposed) Therefore, modern neurobehavioral methods are used in the assessment of the early effects due to exposure to neurotoxic agents in working and general environment21.

Kilburn reported that sensitive testing showed impaired brain functions among acute H2S poisoning survivors who had been unconscious and looked all right after that. Similar impairments were measured in people exposed to amounts below 50 ppm that had not caused unconsciousness19. Accordingly, a series of neurophysiological and neuropsychological testing was carried out in our study. The neurophysiological measured simple reaction time and P300 latency and amplitude while, the neuropsychological testing measured memory impairment (Visual & Logical) and executive frontal functions. 

In our work, the exposed workers showed poor performance of both neurophysiological and neuropsychological tests. As was stated by Kilburn22, diminished performance of these tests denotes persistent cognitive functions impairment.

Additionally, P300 is involved in cognitive processing arising from multiple cortical and subcortical areas, Abnormalities of P300 latency and/ or amplitude are regarded as evidence of impairment of cognitive functions including cortical generator in frontal areas, hippocampus, amygdala as well as brain stem and the thalamic structure23. The mean±SD P300 latency in sewer workers was 487.33±45.23 msec compared to 301.56±17.61 msec in controls (P<0.001). Not surprisingly, delayed evoked brain potentials was accompanied with delayed simple reaction time (377.18±42.47 versus 315.14±29.83) (P<0.001). Variations in P300 latency and simple reaction time could be considered as a consequence of reduced speed resulting from diminished attention24. Reduced attention is documented on one hand by the marked significant reduction of the scores achieved by sewers in both digit span tests (forwards and backwards) and on the other hand, by the statistically significant negative correlation between these two tests and delayed reaction time and P300 latency respectively.

These results are comparable to those of Kilburn's25, who reported prolonged simple reaction time among 43% of chronically exposed population living downwind from wells pumping crude oil and the environmental monitoring to H2S was comparable to occupational exposure levels in our study. In a more recent study by the same author22, similar findings was reported among chronically exposed workers to moderate doses of H2S. On the other hand, delayed P300 latency was reported as residual chronic effect after H2S intoxication without loss of consciousness26.

Frontal executive functions were assessed by design fluency and COWA test, Both tests assess the patient’s ability to generate responses. Performance of this task can be impaired by poor initiation leading to difficulty in response generation and production of minimal number of responses12. Both tests were significantly impaired in exposed workers.

The current mechanistic understanding of H2S toxicity is incomplete and the patho-physiological mechanisms underlying the effect of H2S on normal brain function, particularly, following chronic exposure have yet to be identified27. Direct inhibition of cellular enzymes has been postulated as one of many underlying mechanisms of its toxicity. It has been proposed to be primarily the result of inhibition of cytochrome oxidase, an enzyme critical for cellular mitochondrial respiration. Thus, the electron transport chain is disrupted by preventing oxygen from acting as the final electron acceptor and causing blockage of oxidative metabolism, leading to anaerobic metabolism, decreased ATP production with curtailed cellular energy generation, and the generation of lactic acid. Nervous and cardiac tissues, which have the highest oxygen demand, are especially sensitive to the disruption of oxidative metabolism. Other studies suggested that toxicity results from complex reactions with many other enzymes28.

However, it is suggested that, neurobehavioural effects following long-term exposure is accumulative. That is each exposure results in increased brain damage. The individual damage does not recover, and brain dysfunction continues for years. These observations are supported by research on animals, where it has been shown that accumulative exposures adversely affect cytochrome oxidase enzyme activity and changes in the hippocampal structure19.

A study of ultrastructural and morphometric characteristics of nerve cells and myelinated fibers in the cerebral cortex after chronic exposure to natural gas containing H2S in low concentrations, revealed activation of protein synthesis in nerve cells after chronic exposure to natural H2S-containing gas in low concentrations (10 mg/m(3) by H2S) for 2 weeks. After 1 month, the ultrastructure of myelinated fibers was characterized by sectorial loosening and demyelination29

What adds to the complexity of H2S toxicity, is the existence of a functional genetic polymorphism affecting rhodanese or thiosulfate sulfurtransferase (TST) activity. (TST) is a mitochondrial matrix enzyme that plays roles in the formation of iron-sulfur proteins, the modification of sulfur-containing enzymes, and is also involved in H2S detoxification thus playing role in the individual susceptibility to H2S neurotoxicity30.

As thiosulfate is the major oxidation product of sulfide, urinary thiosullfate was recommended as a biomarker for H2S exposure in many studies31. Moreover, Kage et al.32, stated that thiosulfate in urine is the only indicator of H2S poisoning in non fatal victims., which is then converted to sulfate and subsequently excreted in urine.

This study revealed remarkable increase of the concentrations of urinary thiosulfate among the exposed workers compared to their controls (P<0.001). Similar results were reported by Kage et al.33, when the authors obtained concentrations of urinary thiosulfate 4-14 times higher among H2S exposed workers than the controls.

Hydrogen sulfide does not accumulate in the body and the urinary thiosulfate levels peak approximately 15 hours after exposure and drop to control levels by 17 h post-exposure34. Therefore, the increased concentrations of urinary thiosulfate indicate the continuous daily occupational exposure to H2S among our exposed workers.  However, a quantitative relationship between H2S exposure levels and urinary thiosulfate levels has not been established in many studies32 and this explains the insignificant correlation between the duration of exposure and the concentration level of urinary thiosulfate.

It is worth noting that thiosulfate is not specific to H2S metabolism, as it may result from ingestion of food or water with a high sulfur content leading to increase urinary thiosulfate concentrations34. This fact along with absence of statistically significant correlation between the urinary thiosulfate with any of neurophysiological and neuropsycological parameters used in this study, limit the ability of this biomarker to be an estimate of a threshold level above which exposure is to be stopped.

However, whereas urinary thiosulfate is recommended as exposure biomarker for H2S, irrespective to duration of exposure or to the suspected health effects, specific biomarkers of effect have not been identified. As many studies including ours have documented the cognitive dysfunction following chronic exposure to H2S gas, this work have suggested MMSE test to be a screening test for cognitive dysfunction following chronic occupational exposure to H2S.

The MMSE, has advantages of brevity, easy in administration provide a good rough screening test, which was used to assess the effect of antihypertensive treatment on cognitive functions.35

Although, none of the tested workers had score less than 24 which is considered an evidence for cognitive dysfunction, the mean value of MMSE test for the exposed subjects was 27.09±1.01, which is significantly lower than that of the controls 30±0.0, which can be considered as mild cognitive function impairment after chronic exposure to H2S. Recently, Fango et al.36 obtained lower MMSE score level among H2S exposed subjects but after acute exposures.

Furthermore, correlating the MMSE results with both duration of exposure and the level of urinary thiosulfate showed no significant correlation. This raises the concept of personal susceptibility to neurotoxicity which is related to genetic makeup, other toxic exposure and nutritional status16. 

The significant correlation between MMSE versus digit backward and design fluency tests may recommend it to be used as a valid screening test for cognitive dysfunction and to be added to annually medical examination tests of sewer networks and sewage treatment workers in addition to any occupation that entails exposure to H2S gas.

However, more detailed studies by using functional neuroimaging are still needed to verify the neuroanatomical and neurobehavioral effects resulting from chronic low dose exposure to H2S gas. Additionally, attention should be paid to residential areas nearby oil wells, sewage treatment plants and tanneries where air is potentially polluted with H2S gas.

In conclusion, exposure of sewer network workers is associated with significant cognitive dysfunction which can be screened by applying MMSE as a screening test of the exposed worker.

All workers should undergo periodic (annually) examinations, to reveal early symptoms of possible chronic effects applying MMSE to detect mild cognitive impairment and workers should wear respirator, or gas mask, when exposed to harmful vapors or gases.          

 

 

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18.    Thorn J, Beijer L and R Rylander (2002): Work related symptoms among sewage workers: a nationwide survey in Sweden. Occupational and Environmental Medicine;59:562-566

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الملخــص العربـــى

 

تغيرات الوظائف المعرفية بين عمال شبكات الصرف الصحى المصريين

 

يعتبر غاز كبريتيد الهيدروجين من الغازات السامة التى يمكن أن يتعرض لها عمال شبكات الصرف الصحى.

أهداف البحث: يهدف البحث إلى قياس الخلل في الوظائف المعرفية بين عمال شبكات الصرف الصحى وعلاقة هذه التغيرات إن وجدت بمستوى الكبريتات في البول ( مؤشر التعرض لغاز كبريتيد الهيدروجين). بالإضافة إلى ذلك يهدف البحث الى اتخاذ اختبار فحص الحالة العقلية المختصر (MMSE) كوسيلة لرصد خلل الوظائف المعرفية بين هؤلاء العمال.

عينة الدراسة:  شملت الدراسة 34 عامل من عمال صيانة شبكات الصرف الصحى بالإضافة إلى 21 شخص لم يسبق لهم التعرض لغاز كبريتيد الهيدروجين بصورة مهنية و تم اتخاذ هؤلاء كمجموعة ضابطة.

طريقة البحث: خضع المشاركون فى هذه الدراسة للآتي 1. تاريخ مرضى للأمراض العصبية مع فحص إكلينيكي عصبى. 2. قياس مستوى الكبريتات في البول ( مؤشر التعرض لغاز كبريتيد الهيدروجين). 3. قياس الوظائف المعرفية وذلك بقياس اختبارات فسيولوجية عصبية (زمن رد الفعل البسيط و الجهد المثار P300) و اختبارات فرعية من اختبار ويكسلر المعدل لقياس الذاكرة.

النتائج: 1. ارتفاع معدلات الأعراض العصبية مثل الصداع و اختلال الذاكرة و نقص التركيز. 2. ارتفاع شديد فى مستوى الكبريتات في البول بين العمال المعرضين و لكن بدون ارتباط بينه وبين فترة التعرض. 3. بينت الدراسة سوء أداء العمال المعرضين للاختبارات العصبية المختلفة بالمقارنة بالمجموعة الضابطة بخاصة إطالة زمن رد الفعل البسيط  و الجهد المثار P300. 4. أحرزت نسبة كبيرة من العمال المعرضين نتائج  منخفضة في اختبار فحص الحالة العقلية المختصر (MMSE).

الخلاصة: من الممكن أن يؤدى التعرض لغاز كبريتيد الهيدروجين إلى خلل فى الوظائف المعرفية بين عمال شبكات الصرف الصحى ويمكن هذا الخلل باستخدام اختبار فحص الحالة العقلية المختصر (MMSE).

 



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