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[Exposure to carcinogens in work environment today. State of the art, problems and prospects raised by the Law 626/94].

The implementation in our country of recent legislation on carcinogenic risk assessment and management (VIIth title of Law 626/94) is considered. The authors describe potentialities and limits of the new legislation and of the derived Guidelines issued by the Regions. The health policy in this field and possible evolution in the near future are outlined, bearing in mind the experience of other countries. A short list of questions is suggested as a contribution to the discussion on the future scenario: whether exposure to carcinogens should be lower in the working environment than in the general environment; what is the relative importance of multifactoriality, individual biological variability, individual life-style in the genesis of cancers; whether medical health surveillance is worthwhile in terms of primary prevention; is it always true that there is no threshold limit value for carcinogens; what is the role of individual attitudes to prevention in exposure to carcinogens compared to "objective" protection; which balance between costs and benefits should be aimed at.

Carcinogens, Environmental↗

Development of a fiber optic probe to measure NIR Raman spectra of cervical tissue in vivo.

The goal of this study was to develop a compact fiber optic probe to measure near infrared Raman spectra of human cervical tissue in vivo for the clinical diagnosis of cervical precancers. A Raman spectrometer and fiber optic probe were designed, constructed and tested. The probe was first tested using standards with known Raman spectra, and then the probe was used to acquire Raman spectra from normal and precancerous cervical tissue in vivo. Raman spectra of cervical tissue could be acquired in vivo in 90 s using incident powers comparable to the threshold limit values for laser exposure of the skin. Although some silica signal obscured tissue Raman bands below 900 cm-1, Raman features from cervical tissue could clearly be discerned with an acceptable signal-to-noise ratio above 900 cm-1. The success of the Raman probe described here indicates that near infrared Raman spectra can be measured in vivo from cervical tissues. Increasing the power of the excitation source could reduce the integration time to below 20 s.

Biopsy↗

Study of asbestos exposure in some applications of asbestos materials in the chemical industry.

This study is designed to determine the effects of short-term asbestos exposure on workers in the production of asbestos gaskets and filter materials for technological equipment in the chemical industry. The workers from the "Cathode workshop", "Diaphragm electrolysis", "Polymers" Co., Devnja (12 operators) who operate the installation of asbestos diaphragms manufacture and installation of electrolysis cells, and the staff of the "Mechanical" shop of "Nephtochim" Co., Burgas, engaged in the cutting of gaskets made of pressed asbestos-polymer boards (6 workers), were studied. The hygienic normative standards and methodology for measuring and assessment of the asbestos exposure, used all over the world were applied: mean shift count concentration of respirable asbestos fibres; entire shift personal sampling (BSS 2200-85), PCOM light microscopy (BSS 16909-89). The level of asbestos exposure registered was in the range 0.04 to 0.38 f/cm3 for the operators in the "Diaphragm electrolysis" shop and for the staff in the "Mechanical" shop of "Nephtochim" Co. from 0.04 to 0.43 f/cm3. The established concentrations are acceptable according to the requirements of the official hygienic threshold limit value (TLV) in Bulgaria (1 f/cm3), but because asbestos is a human cancerogen and there is tendency for regular revision with the intention of decreasing the hygienic TLV, the asbestos occupational exposure of these groups of workers cannot be accepted as safe. The statements made increase the necessity of dust control by technical preventive means and the medical control of the workers exposed to asbestos-related injuries.

Asbestos↗

A comparative assessment of liver function in workers in the petroleum industry.

OBJECTIVES: The group studied included 666 workers from the benzene (n = 30), xylenes (n = 144), ethylene oxide (n = 91), 1,3-butadiene (n = 110) and transport and mechanisation (n = 82) departments of a petrochemical plant in Bulgaria. The leading hazards for the particular departments are as follows: Benzene: benzene (up to ten times the threshold limit value; TLV): xylenes: benzene (up to nine times TLV) and xylenes (up to 1.6 times TLV); ethylene oxide: ethylene oxide (up to 20 times TLV) and ethylene (up to 30 times TLV); divinyl: 1,3-butadiene (five times TLV) and acetonitrile (six times TLV); transport and mechanisation: benzene, xylenes and pentane (0.7-10 times TLV). METHODS: The functional status of the liver was assessed by clinical (medical check-up), echographic and biochemical (ASAT, ALAT, APh, gamma-GT, lipid fractions, reduced glutathione and SH groups) investigations. Biochemical analyses were performed with POINTE 190 (USA). The results obtained were compared with those of a control group (n = 150), consisting of subjects with no occupational exposure to chemical hazards. RESULTS: Comparisons showed that the metabolic disturbances determined were most significant in workers from the ethylene oxide department. Significant decreases in the serum levels of reduced glutathione (up to 48%) and of thiol groups (with 23%), increased enyzme activity (up to 18%) and lipid fractions (up to 24%) were observed. In the benzene and xylenes departments, deviations in the indices studied were equally manifest. In workers exposed to 1,3-butadiene, the changes in lipid indices were prevalent (registered in 25% of the studied persons). The staff in transport and mechanisation showed deviations in enzyme indices at a slight increase of the lipid fractions. The changes determined in serum biochemical characteristics corresponded to the clinical findings--hepatomegaly, confirmed echographically in 10%-20% in the different departments. CONCLUSIONS: The results obtained followed the exposure-response relationship. The deviations registered in workers with a length of service of more than 10 years were the most significant. The occupational genesis of the determined disturbances was confirmed in 11 subjects.

Adult↗

An assessment of the exposure of technicians working in a chemical laboratory for aromatic hydrocarbons at Neftochim, Burgas.

The average exposure to aromatic hydrocarbons per working shift of laboratory assistants at a chemical laboratory were measured. The laboratory is one of the service departments for four different production departments at Neftochim, Burgas--the largest oil refinery in Bulgaria. Long-term sampling of the air from different workplaces in the laboratory was performed by sampling charcoal sorbent tubes (type CT-CN-2), manufactured by Higitest (type NIOSH). The concentration of benzene, toluene, ethyl benzene, xylene and isopropyl benzene in the air at the laboratory was determined by gas chromatography using the Varian MEGA 1 with a flame ionisation detector and Inowax capillary column. The measured exposure levels of toxic substances in the aromatic hydrocarbons analysis laboratory were as follows: Benzene, 0.15-1.3 mg/m3, in single samples its concentration was 4.06-8.63 mg/m3; toluene, 0.15-0.46 mg/m3, in single samples its concentration was 5.5-15.62 mg/m3; ethyl benzene in most samples was 0.02 mg/ m3, in single samples its concentration was 20.68 mg/m3; xylene in most samples was 0.4 mg/m3, in single samples its concentration was 0.51-1.68 mg/m3; isopropyl benzene in most samples was 0.1 mg/m3, in single samples its concentration was 0.20-1.12 mg/m3. The results, obtained by measuring the average work-shift exposure of laboratory assistants to aromatic hydrocarbons in the air at the analytical laboratories, show that the measured concentrations are smaller than the respective threshold limit values. Bearing in mind, however, that some of these substances have an effect on the human organism, exposure to them is excessively hazardous for laboratory technicians.

Bulgaria↗

Specifity and sensitivity of the inhibition of drug metabolism following inhalation of carbon disulphide-air mixtures.

A single 8-h exposure of adult female Wistar rats to 20 ppm carbon disulphide (CS2), the threshold limit value (TLV) in several countries, was sufficient to cause inhibition of the following drug-metabolizing reactions: formation of trichloroethanol and trichloroacetic acid from trichloroethylene (aliphatic C-hydroxylation), formation of 4-hydroxyantipyrine from antipyrine (quasi-aromatic C-hydroxylation), formation of acetaminophenol from acetanilid (aromatic C-hydroxylation) and phenacetin (oxidative odealkylation), respectively, and formation of 4-aminoantipyrine from aminopyrine (oxidative N-demethylation). The behaviour of these effects was dependent on the dose of CS2 administered in that the inhibitory process was enhanced when increasing the concentration to (50), 100, 200, and 400 ppm. The respective changes could be demonstrated by a short-duration (6-h) reduction in the urinary excretion of the metabolites. In the case of trichloroethylene the limitation in metabolite formation persisted for as long as 36 h due to the varying rate of formation of trichloroethanol and trichloroacetic acid. This deficiency in excretion was compensated in part during the subsequent elimination phase (up to 24 and 36 h, respectively), an observation which suggests the rapid reversibility of the alteration. As shown by the respective prolongation of the hexobarbital sleeping time in the rat, the side-chain oxidation of hexobarbital to ketohexobarbital was increasingly inhibited by rising concentrations of CS2 in the range of 20 to 400 ppm/8 h. On the basis of the present results it is concluded that CS2 also inhibits various oxygenases of the microsomal enzyme system. In adult female NMRI mice a significant inhibition of the microsomal procaine-hydrolyzing esterase of the liver was observed only after 400 ppm/8 h; however, this limitation did not affect the LD50 of procaine-HCl, particularly as the corresponding serum esterase activity also remained uninfluenced. The aromatic N-acetylation of sulphisomidine and the quasi-aromatic N-acetylation of 4-aminoantipyrine in rats failed to be significantly reduced by CS2 even after 400 ppm/8 h, nor did the same dose of CS2 affect the glucuronidation of 4-hydroxyantipyrine in the same animal species. It is concluded from the above results that the specificity and sensitivity of the inhibition of drug metabolism observed in small laboratory animals is probably similar to that prevailing in man. This assumption has already been substantiated for the oxidative N-demethylation of aminopyrine.

Acetanilides↗

[Determination of the anaerobic threshold in chronic cardiac failure. Value and limitations].

Anaerobic threshold was studied in 35 patients with cardiac failure present for more than 6 months, of primary or ischemic origin and New York Heart Association Stage II or III. Each patient underwent an exercise test of ergometric bicycle (increments of 10 watts/1 minute) with analysis of expired gases respiratory cycle by respiratory cycle (oxygen consumption, carbon dioxide production, respiratory oxygen and carbon dioxide equivalent, respiratory quotient). Anaerobic threshold was determined indirectly following Wasserman's recommendations. It was possible to determine anaerobic threshold in 25 patients (83.3%). The test was well tolerated. The two best methods for detection of anaerobic threshold were divergence of the curve of production of carbon dioxide in relation to oxygen consumption and an increase in respiratory oxygen equivalent while the carbon dioxide equivalent remained constant. In addition, oxygen consumption at the anaerobic threshold was statistically correlated with functional class (p < 0.05) and with the Weber classification based upon peak oxygen consumption (p < 0.001). Finally, anaerobic threshold occurred on average at 5.4 +/- 1.8 min from the start of exercise with a heart rate of 119.7 +/- 18 bpm, an oxygen consumption of 10.5 +/- 2.3 ml/min/kg (i.e. 43.2 +/- 12.1% of maximum oxygen consumption and 70.5 +/- 19.3% of oxygen consumption limited by symptoms) and a respiratory quotient of 1.07 +/- 0.08. In conclusion, analysis of respiratory gases during exercise in cardiac failure patients enables, with sub-maximal exercise and noninvasively, the determination in the majority of cases of anaerobic threshold, which is statistically correlated with New York Heart Association stage and the Weber classification based upon oxygen consumption at peak effort.

Adult↗

Limited value of anaerobic threshold for assessing functional capacity in patients with heart failure.

Exercise tolerance was assessed in 146 patients with cardiac dysfunction in terms of anaerobic threshold (ATge). Patients were divided into four classes according to the peak oxygen uptake: Class A (72 patients) exceeding 1000 ml/min; Class B (27 patients) 800-999 ml/min; Class C (37 patients) 500-799 ml/min; and Class D (10 patients) below 500 ml/min. An incidence of the ATge breakpoint was lower in patients of Class C (38%) than in those of either Class B (70%, p < 0.05) or Class A (87%, p < 0.05). The ATge could not be determined in any patients in Class D. The V-slope method improved the ability to determine ATge by 20%. In Classes C and D, ATge detection was precluded considerably by the fact that the initial workloads of exercise test involved oxygen uptake levels already close to or above the ATge. An oscillatory hyperventilation pattern was also significantly related to failure in defining ATge in Class C patients. Of the 51 patients whose ATge was undetermined, 9 had an atrial septal defect. In two of these, exercise-induced right-to-left shunting led to progressive arterial hypoxemia, and the consequent hyperventilation masked the appearance of ATge. Thus, ATge is virtually undetectable in patients with severe heart failure largely because of the early onset of anaerobic metabolism or abnormal ventilatory responses to exercise. Accordingly, the clinical application of ATge in the assessment of functional capacity would be limited to patients with mild to moderate heart failure.

Adult↗

The Mine Safety and Health Administration's criterion threshold value policy increases miners' risk of pneumoconiosis.

BACKGROUND: The Mine Safety and Health Administration (MSHA) proposes to issue citations for non-compliance with the exposure limit for respirable coal mine dust when measured exposure exceeds the exposure limit with a "high degree of confidence." This criterion threshold value (CTV) is derived from the sampling and analytical error of the measurement method. CONCEPTUAL FRAMEWORK: This policy is based on a combination of statistical and legal reasoning: the one-tailed 95% confidence limit of the sampling method, the apparent principle of due process and a standard of proof analogous to "beyond a reasonable doubt." CRITIQUE: This policy raises the effective exposure limit, it is contrary to the precautionary principle, it is not a fair sharing of the burden of uncertainty, and it employs an inappropriate standard of proof. Its own advisory committee and NIOSH have advised against this policy. For longwall mining sections, it results in a failure to issue citations for approximately 36% of the measured values that exceed the statutory exposure limit. DISCUSSION: Citations for non-compliance with the respirable dust standard should be issued for any measure exposure that exceeds the exposure limit.

Dust↗

Trichloroethylene in urine as biological exposure index.

Occupational exposure to trichloroethylene (TRI) was studied by analysis of environmental air and urine from 49 workers operating in a special printing house on glass. For the measurement of environmental concentration of TRI (Cenv), the ambient air was sampled using personal passive dosimeters. The activated charcoal was desorbed with carbon disulfide and injected into a gas-cromatograph - mass spectrometer (GC-MSD). The biological monitoring of exposed workers was conducted by determining the concentration of TRI in urine (Curine) Urine concentration of TRI was determined by headspace analysis using GC-MSD. Significant correlation was found between the environmental TRI concentration and urinary TRI concentration. The use of a regression equation between Curine (microg/l) and Cenv (mg/m3) (Curine = 0.081 x Cenv + 4.27) resulted in a value of Curine corresponding to Threshold Limit Value-Time Weighted Average (TLV-TWA) exposure value (269 mg/m3) of 26.0 microg/L.

Adult↗

[Effect of acupuncture and massage at tendon on F-wave of electromyogram in the patient of flexor spasm of the upper limb after operation of cervical spondylosis].

OBJECTIVE: To explore the mechanism of acupuncture and massage at the tendon in treatment of the upper limb flexor spasm after cervical operation. METHODS: Fifty-six cases were randomly divided into a treatment group (n = 30) treated with acupuncture and massage at the tendons, and a control group treated with traditional acupuncture and medication. Changes of F-wave, time limit and threshold value in electromyogram before and after treatment were investigated in the both groups. RESULTS: Before treatment, the F-wave in the patient of the upper limb spasm post-cervical operation was characterized by high amplitude, long time limit and low threshold value, with no significant difference between the two groups (P > 0.05); after treatment, the amplitude lowered (P < 0.01), the time limit shortened (P < 0.001) in the treatment group and no significant changes were found in the control group (P > 0.05), but the amplitude of F-wave in the treatment group was significantly lower than that in the control group (P < 0.05). The threshold value significantly increased in the two groups, with the treatment group more significantly increased than the control group (P < 0.05). CONCLUSION: Acupuncture and massage at tendons can relieve the spasm through lowing the excitement in the cells of the anterior horn of the spinal cord, decreasing the amplitude and time limit of the F-wave, increasing the threshold value and reducing traction reflection.

Acupuncture Therapy↗

The role of coagulase-negative Staphylococcus spp. and associated somatic cell counts in the ovine mammary gland.

The somatic cell count (SCC) of ewes' milk was determined by the Fossomatic method and compared with the bacteriological status of the mammary gland. Of 366 samples from uninfected udder halves, 64.5% had SCC less than 50 x 10(3) cells/ml, 81.9% had SCC less than 250 x 10(3), and 92.4% had less than 500 x 10(3) cells/ml. Of 130 bacteriologically positive samples, 91.1% had SCC more than 500 x 10(3) cells/ml and 98.8% more than 250 x 10(3). Of the examined milk samples 26.2% showed positive bacteriology during the single sampling. The most frequent pathogens isolated from the milk samples were coagulase-negative staphylococci. Considering our results, 250 x 10(3) cells/ml should be the threshold value, which could be regarded as the upper limit for normal SCC of ewes' milk.

Animals↗

Application of the threshold of toxicological concern concept to pharmaceutical manufacturing operations.

A scientific rationale is provided for estimating acceptable daily intake values (ADIs) for compounds with limited or no toxicity information to support pharmaceutical manufacturing operations. These ADIs are based on application of the "thresholds of toxicological concern" (TTC) principle, in which levels of human exposure are estimated that pose no appreciable risk to human health. The same concept has been used by the US Food and Drug Administration (FDA) to establish "thresholds of regulation" for indirect food additives and adopted by the Joint FAO/WHO Expert Committee on Food Additives for flavoring substances. In practice, these values are used as a statement of safety and indicate when no actions need to be taken in a given exposure situation. Pharmaceutical manufacturing relies on ADIs for cleaning validation of process equipment and atypical extraneous matter investigations. To provide practical guidance for handling situations where relatively unstudied compounds with limited or no toxicity data are encountered, recommendations are provided on ADI values that correspond to three categories of compounds: (1) compounds that are likely to be carcinogenic, (2) compounds that are likely to be potent or highly toxic, and (3) compounds that are not likely to be potent, highly toxic or carcinogenic. Corresponding ADIs for these categories of materials are 1, 10, and 100 microg/day, respectively.

Animals↗

Variation of biological responses to different respirable quartz flours determined by a vector model.

BACKGROUND: The hypothesis of widely differing lung damage due to commonly used types of quartz was studied in 16 samples of respirable quartzes (> 99% silica) from sites of the European quartz industry, using an in vitro test, the vector model. Two samples with high and 2 with low biological activities were identified and subsequently examined for their in vivo lung toxicity (inflammation, fibrosis, genotoxicity) and surface characteristics. Alveolar macrophages (AM) are considered the target cells of primary dust effects. The vector model mimics some of the elemental dust cell effects such as cell toxicity, effects on the metabolism and stimulatory effects, e.g., TNF alpha and dust-induced ROS secretion. METHODS: Doses of 15, 30, 60 and 120 microg dust per 10(6) AM were used together with the control dusts (quartz DQ12 and corundum). Testing parameters were LDH, glucuronidase, PMA forced ROS release, TNF alpha and dust induced ROS secretion. The main criterion for the selection of low or high activity samples was the secretion of TNF alpha. RESULTS: (i) Apart from quartz samples with an activity close to that of DQ12, one also finds examples with a very low activity. (ii) In comparison particular parameters are linked with a specific dose response relationship and different dose points for the leveling off of the effects. The levels of TNF alpha represent a conspicuously broad response pattern; some samples induce secretion at the lowest dose and others are not active even at the highest dose investigated at already apparent toxicity. (iii) Regarding various parameters the dust samples led to distinct dose response profiles considered as vectors. The current study indicates that within the particle type "quartz fine dust" varying harmful doses and different elements of damage must be present. (iv) The lung damage of the subchronic animal assay coincides with in vitro tests thus confirming the concept of the vector model. CONCLUSION: Threshold effects in the range of 15 - > or = 120 microg can be demonstrated for the discriminant vector TNF alpha, i.e. over 4 steps of dose doubling. These studies show very toxic quartzes but also quartzes of low biological activity comparable to corundum.

Animals↗

Reference data for evaluation of occupationally noise-induced hearing loss.

Relevant reference data are required in order to determine the effect from occupational noise exposure on hearing. Pure-tone averages (PTA) of hearing threshold levels simplify the evaluation for audiometric frequencies typically affected by noise. The present study provides reference data of high frequency (HF) PTA over 3, 4 and 6 kHz for a general adult population, aged from 20 to 79 years, not exposed to hazardous occupational noise. The results are presented as statistical distributions of HF PTA values as functions of age, and as prevalence of different degree of HF PTA in the age groups 20-29, 30-39, 40-49, 50-59, 60-69 and 70-79 years.

Adult↗

Basic variables at different positivity thresholds of a quantitative immunochemical test for faecal occult blood.

OBJECTIVES: Screening by faecal occult blood testing (FOBT) is effective in decreasing mortality and incidence of colorectal cancer (CRC). Immunochemical tests have proved to be more cost effective than guaiac FOBTs. The latex agglutination test (LAT) has the advantage of being a fully automated, quantitative test. The aim of this study is to interpret the overall experience with LAT according to different positivity thresholds. SETTING: A population based screening programme is currently running involving subjects aged 50-70, invited every 2 years to have an FOBT. LAT is the standard screening test and has a positivity threshold for further diagnostic tests of 100 ng haemoglobin/ml of sample solution. METHODS: Positivity rates, detection rates for CRC high risk adenomas, and positive predictive values for CRC, high risk adenomas, and low risk adenomas were calculated for several positivity thresholds. RESULTS: 19,132 attendances at screening were recorded (11,774 at first screening, 7358 at subsequent screenings). Progressively increasing the positivity threshold from 100 to 200 ng/ml showed (a) a decrease in positivity rate; (b) a decrease in detection rates for CRC or high risk adenomas; (c) an increase in positive predictive values for cancer; (d) an increase in positive predictive value for high risk adenomas. CONCLUSIONS: Increasing the positivity threshold of the LAT reduces recall rate and improves positive predictive value for cancer or high risk adenomas but substantially decreases the detection rate of CRC and high risk adenomas. For this reason increasing the positivity cut off for LATs is not advisable. On the other hand decreasing the positivity threshold would increase recall rate and sensitivity of screening. Careful evaluation of sensitivity of the quantitative results of the LAT for interval cancers is needed to definitively assess the optimal positivity threshold for LATs in population based screening programmes.

Adenoma↗

Establishing a practical blood platelet threshold to avoid reporting spurious potassium results due to thrombocytosis.

BACKGROUND: Thrombocytosis is one of several pre-analytical factors which contribute to spuriously high serum potassium concentrations, yet there is little published data to guide analysts in the selection of a specific platelet count threshold above which serum potassium results become unreliable. We have studied the sensitivity and specificity of blood platelet count as a predictor of false elevations in potassium. METHODS: Paired serum and plasma potassium measurements together with full blood count were performed for 300 patients. All samples were stored at room temperature and analysed within 4 h of collection. The difference between serum and plasma potassium was plotted against blood platelet count. RESULTS: When the difference (serum-plasma) in potassium concentration was plotted against platelet count, there was a direct linear relationship. Blood platelet counts of >500 x 10(9)/L will detect elevations in serum relative to plasma potassium of >0.5 mmol/L, with a sensitivity of 71% and a specificity of 89%. CONCLUSION: It is recommended that where blood platelet count is above 500 x 10(9)/L, potassium measurements should be repeated using lithium heparin plasma. When serum potassium results of >5.4 mmol/L are obtained, it is our policy to check the platelet count if a sample is available before reporting results. If available and above 500 x 10(9)/L, potassium results are withheld and plasma requested.

Adult↗