Setting occupational exposure limits for pharmaceuticals

This work was undertaken to improve conditions for in vitro maturation and activation of porcine oocytes. Experiments were designed to compare: (i) electrical pulse frequency, (ii) methods of oocyte preparation, (iii) maturation conditions, and (iv) electrical poration medium on development. Oocytes were harvested by follicle dissection or aspiration, co-cultured with follicle shells in M199 based medium with or without media changes at 38.5 degrees C in 5% CO2 under non-static conditions for 48 h and electroactivated using single or multiple pulses (current strength 1.0 kV/cm for 50 microseconds in 0.28 M inositol or mannitol based media with 10 mM histidine) at different time intervals. The results showed: (i) neither the pulse frequency nor the pulse interval influenced rates of pronuclear formation but multiple pulse activation (3 pulses at 5 min intervals) induced a higher incidence of development and progression through the 4-cell block in contrast to one pulse activation; (ii) both the rate of nuclear maturation (88.6% vs. 77.6%) and post-activation cleavage (89.8% vs. 67.4%) were higher (P < 0.05) when oocytes were collected by follicle dissection rather than by aspiration; (iii) while changing to a hormone-free medium at 24 h was without effect on maturation (91.9% vs. 91.7%), rate of cleavage (81.6% vs. 72.3%, P < 0.05) at 24 h was enhanced by the medium change; and (iv) oocytes activated with 3 pulses 5 min apart in mannitol based medium at 48-49 h and at 53-54 h formed pronuclei at a comparable rate but subsequent parthenogenetic development was higher in the older eggs. By contrast, inositol-based medium supported development of young and old eggs equally well. Calcium and magnesium ions are, however, necessary in both mannitol and inositol media for activation of porcine oocytes matured in vitro. The present results suggest that optimal parthenogenetic activation and early development of IVM pig oocytes could be obtained if oocytes are harvested by dissection, cultured for 24 h in hormone-containing medium before being placed in hormone free medium and activated at 48 h in inositol based medium using a three pulse activation system.     

Industry''s perception and use of occupational exposure limits

OBJECTIVE: To examine posttraumatic stress disorder (PTSD) in mothers of survivors of childhood cancer. Comorbidity of anxiety and depressive disorders, prevalence of subclinical PTSD, and the utility of a self-report measure as a screening instrument for PTSD were also investigated. METHOD: Mothers (n = 65) completed a questionnaire self-report PTSD checklist (PCL-C). Mothers were administered several modules of the SCID: nonpatient edition by telephone, including the PTSD, Generalized Anxiety, and Major Depressive Disorder modules. RESULTS: We diagnosed 6.2% of the sample with current PTSD. An additional 20% had subclinical PTSD. One of four mothers with PTSD diagnoses had a comorbid diagnosis of an anxiety and depressive disorder. The PCL-C evidenced diagnostic utility as a screening instrument. However, a moderate number of false-positives would result if the recommended cut-off on the instrument was used. CONCLUSIONS: The PCL-C had diagnostic utility in screening mothers of childhood cancer survivors. The presence of comorbid diagnoses such as anxiety and depression should be examined.     

The development of occupational exposure limits for chemical substances in China

This paper presents a comprehensive review of the occupational exposure limits (OELs) of chemical substances in China. It provides historical background on the development of OELs in this country, with a complete list of traditionally adopted and newly developed OELs for chemicals in workplaces. The philosophical thoughts, the administrative system, the scientific protocols for setting and amending health standards, with emphasis on making health a basic criterion for setting health standards, strengthening epidemiological studies of the human population, integrating epidemiological and toxicological studies, considering technological and economical feasibilities, and making full use of literature information sources are discussed. Further perspectives with respect to practical issues of maximum allowable concentration and time-weighted average, selection of safety factors, and establishment of biological exposure limits are also considered, with the authors' contributions to a discussion on these topics.     

Brain cancer and occupational exposure to lead

A recent report in the literature suggested a link between occupational exposure to lead and brain cancer. To explore the hypothesis, we applied a job-exposure matrix for lead to the occupation and industry codes given on the death certificate of 27,060 brain cancer cases and 108,240 controls who died of non-malignant diseases in 24 US states in 1984-1992. Brain cancer risk increased by probability of exposure to lead among Caucasian men and women with high-level exposure, with a significant twofold excess among Caucasian men with high probability and high level of exposure to lead (odds ratio = 2.1; 95% confidence interval, 1.1-4.0). Risks were also elevated in the low- and medium-probability cells for African-American men with high-level exposure to lead. Trend by intensity level was statistically significant among African-American men (all probabilities combined). Although exposure assessment was based solely on the occupation and industry reported on the death certificate, these results add to other epidemiologic and experimental findings in lending some support to the hypothesis of an association between occupational exposure to lead and brain cancer risk. Analytic studies are warranted to further test this hypothesis.     

Pulmonary fibrosis and occupational exposure to aluminum

Many reports of respiratory disease attributable to aluminum exposure have appeared in the European medical literature during the last 50 years. Great Britain and Germany are two major industrialized nations that acknowledge a causal relationship between occupational exposure to aluminum and respiratory impairment. For factory workers in these countries, pulmonary disease attributed to respirable aluminum particulates is compensated as a workplace disability. In North America, however, there is a lack of consensus regarding the pathogenicity of aluminum fumes and dust to the worker. This view may be based on a difference in the types of industrial usage, the updated methods of aluminum processing in this country, or the benefits of a modern workplace. It has also been proposed that the development of aluminum-induced pulmonary disease may depend on a particular host factor that has not yet been identified. We describe a patient whom we believe developed severe respiratory compromise and irreversible pulmonary fibrosis from a lifetime of industrial aluminum exposure.     

Prevention strategies for occupational low back pain

Ethnic comparisons are extremely important and useful for studying the HLA component involved in insulin-dependent diabetes mellitus (IDDM) predisposition. To date there have been only a few reports on the association of HLA loci and IDDM in Chinese. We report here a study on DQA1*Arg52, DQB1*nonAsp57, and DRB1*04 in IDDM children and control adults among Han Chinese living in Taiwan. One hundred and fourteen unrelated children (62 boys) with IDDM were studied. Their ages at diagnosis were between 0.3 and 15.0 years (6.8 +/- 3.6 years). The control population consisted of 120 randomly selected normal adults. DQA1*Arg52(+/+), DQB1*nonAsp57(+/+), and DRB1*04(+/-) were associated with IDDM (RR = 11.50, 2.21, and 2.82; p = 1.11 x 10(-15), 2.84 x 10(-3), and 1.98 x 10(-4), respectively). DQA1*Arg52, DQB1*nonAsp57, and DRB1*04 conferred risks for IDDM (RR = 12.79, 7.11, and 2.83; pc = 8.22 x 10(-4), 5.35 x 10(-3), and 5.68 x 10(-4), respectively). Combinations of DQA1*Arg52 and DRB1*04 conferred the highest risk for IDDM (RR = 19.64, pc = 5.4 x 10(-5)). DQA1*Arg52 was associated with IDDM in subjects with DQB1*nonAsp57+ (RR = 14.87, pc = 2.41 x 10(-4)) and DQB1*nonAsp57 was also associated with IDDM in subjects with DQA1*Arg52+ (RR = 8.41, pc = 1.54 x 10(-3)), suggesting that DQA1*Arg52 and DQB1*nonAsp57 are interacting. This study demonstrates that DQA1*Arg52, DQB1*nonAsp57, and DRB1*04 confer susceptibility for IDDM to Chinese children. A combination of DQA1*Arg52 and DRB1*04 confers the highest risk and it is suggested that a susceptibility gene might be situated between DQA1*Arg52 and DRB1*04 or both are synergistic. There is an interaction between DQA1*Arg52 and DQB1*nonAsp57 and homozygosity for DQA1*Arg52/DQB1*nonAsp57, which encodes four susceptibility DQ heterodimers, confers a high risk.     

Cost-effectiveness of chemoprophylaxis after occupational exposure to HIV

OBJECTIVES: To assess the economic efficiency of recent US Public Health Service recommendations for chemoprophylaxis with a combination of antiretroviral drugs following high-risk occupational exposure to human immunodeficiency virus (HIV). To provide a framework for evaluating the relative effectiveness and costs associated with candidate postexposure prophylaxis (PEP) regimens. METHODS: Standard techniques of cost-effectiveness and cost-utility analysis were used. The analysis compares the costs and consequences of a hypothetical, voluntary combination-drug PEP program consisting of counseling for all HIV-exposed health care workers, followed by chemoprophylaxis for those who elect it vs an alternative in which PEP is not offered. A societal perspective was adopted and a 5% discount rate was used. Hospital costs of recommended treatment regimens (zidovudine alone or in combination with lamivudine and indinavir) were used, following the dosing schedules recommended by the US Public Health Service. Estimates of lifetime treatment costs for HIV and acquired immunodeficiency syndrome were obtained from the literature. Because the effectiveness of combination PEP has not been established, the effectiveness of zidovudine PEP was used in the base-case analyses. MAIN OUTCOME MEASURES: Net PEP program costs, number of HIV infections averted, cost per HIV infection averted, and cost-utility ratio (net cost per discounted quality-adjusted life-year saved) for zidovudine, lamivudine, and indinavir combination PEP. Lower bounds on the effectiveness required for combination regimens to be considered incrementally cost saving, relative to zidovudine PEP alone, were calculated. Multiple sensitivity and threshold analyses were performed to assess the impact of uncertainty in key parameters. RESULTS: Under base-case assumptions, the net cost of a combination PEP program for a hypothetical cohort of 10,000 HIV-exposed health care workers is about $4.8 million. Nearly 18 HIV infections are prevented. The net cost per averted infection is just less than $400,000, which exceeds estimated lifetime HIV and acquired immunodeficiency syndrome treatment costs. Although combination PEP is not cost saving, the cost-utility ratio (about $37,000 per quality-adjusted life-year in the base case) is within the range conventionally considered cost-effective, provided that chemoprophylaxis is delivered in accordance with Public Health Service guidelines. Small incremental improvements in the effectiveness of PEP are associated with large overall societal savings. CONCLUSIONS: Under most reasonable assumptions, chemoprophylaxis with zidovudine, lamivudine, and indinavir following moderate- to high-risk occupational exposures is cost-effective for society. If combination PEP is minimally more effective than zidovudine PEP, then the added expense of including lamivudine and indinavir in the drug regimen is clearly justified.     

Performance-based exposure control limits for pharmaceutical active ingredients

Numerous hypospadias correction techniques were described in the literature. The technique varies according to the position of the meatus and the importance of the chordee. These new techniques and the care taken in the manipulation of the tissues tend to decrease complications like stenoses and fistulas, frequent in the long urethroplasty. The correction of hypospadias should conform to aesthetic and plastic surgery. More than 300 corrections were carried out in our service. Surgical technique varied in the long run. Currently, we choose as often as possible a correction in one time: release of the chordae and urethroplasty. Straightening of the penis is obtained on one hand by release of the cutaneous chordae and wide dissection of the hypoplastic urethral plate and one or more dorsal plications according to Nesbit are carried out if it proves necessary. In the distal, glandular and coronal forms, the correction is of type M.A.G.P.I. (meatal advancement, glanduloplasty). The complication rate is extremely low. The aesthetic and functional result is very satisfactory. In the proximal forms, Duckett technique is used only in the obligatory cases given the large number of complications. It is generally replaced by Onlay technique. The urethral plate is left in continuity and serves as support to the pedicled and vascularized flap. In the intermediate situations with a middle shaft hypospadias, Mathieu technique is again of application. The aesthetic and functional result of this type of surgery requires good knowledge and careful application of the technique adapted to each case.     

Renal cell cancer correlated with occupational exposure to trichloroethene

A previous cohort-study in a cardboard factory demonstrated that high and prolonged occupational exposure to trichloroethene (C2HCl3) is associated with an increased incidence of renal cell cancer. The present hospital-based case/control study investigates occupational exposure in 58 patients with renal cell cancer with special emphasis on C2HCl3 and the structurally and toxicologically closely related compound tetrachloroethene (C2Cl4). A group of 84 patients from the accident wards of three general hospitals in the same area served as controls. Of the 58 cases, 19 had histories of occupational C2HCl3 exposure for at least 2 years and none had been exposed to C2Cl4; of the 84 controls, 5 had been occupationally exposed to C2HCl3 and 2 to C2Cl4. After adjustment for other risk factors, such as age, obesity, high blood pressure, smoking and chronic intake of diuretics, the study demonstrates an association of renal cell cancer with long-term exposure to C2HCl3 (odds ratio 10.80; 95% CI: 3.36-34.75).     

Behavioral determinants of occupational exposure to chemical agents.

Used the passive-active dimension of the job demand–control model (T. Theorell and R. A. Karasek, see record 83:28881) to examine the impact of behavioral factors on the exposure to and actual uptake of airborne lead in 2 lead exposed populations of male workers (18 from an electric accumulator factors and 18 from a lead smeltery) and to ascertain work-related determinants of hygienic behavior. Environmental exposure was assessed by measurement of the concentration of lead dust in ambient air at the workplace, and the intake of lead was assessed by measurement of the lead in blood level. In the work environment of Ss in active jobs, lower concentrations of lead in air were measures, but higher levels of lead in blood were observed in these workers. The opposite was true of workers in passive jobs. Differences in hygienic behavior (e.g., use of protective equipment) at work may explain these results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hemorheology in occupational lead exposure

OBJECTIVES: The purpose of this investigation was to study hemorheological parameters in occupationally lead exposed men. MATERIAL AND METHODS: For 15 clinically healthy lead-exposed male subjects [age 34.6 (SD 8) years] the viscous (epsilon') and elastic (epsilon") components of whole blood viscosity corrected for 45% hematocrit were measured for shear rates between 1.s-1-100.s-1 at 37 degrees C. Moreover, lead concentrations in blood and urine and the delta-aminolevulinic acid dehydrase level were determined. Fifteen unexposed age-matched men were used as referents. RESULTS: The mean lead concentration in the blood and urine of the lead-exposed men was 48.7 (SD 16.2) micrograms. dl-1 and 38.8 (SD 17.1) micrograms.g creatinine-1, respectively. While epsilon" was significantly increased only at low shear rates, epsilon' was elevated throughout the investigated shear range in comparison with the values of the unexposed referents. These results are characteristic of erythrocytes with enhanced rigidity. The aggregation and filtration index of erythrocytes were significantly elevated for the lead-exposed workers. A positive correlation existed between lead in blood and epsilon' or epsilon", whereas delta -aminolevulinic acid dehydrase and epsilon' or epsilon" were inversely correlated. No differences in plasma viscosity or in lipid status could be detected. CONCLUSION: Increased blood lead concentrations can be considered an additional risk factor for vascular diseases predisposing towards microvascular occlusion.     

Respiratory effects of occupational exposure to an epoxy resin system

A standardized respiratory questionnaire and pulmonary function tests were used to examine thirty-four employees of a snow-ski manufacturing plant, including twenty-five workers who were exposed to an epoxy resin system containing the amine hardener 3-dimethylamino propylamine (3-DMAPA). Maximum expiratory flow-volume curves were obtained on Monday and Thursday, before and after each shift, and FVC, FEV1.0, MEF50%, and MEF25% were caculated. Environmental measurements of the total amine levels were found to range from 0.41 to 1.38 ppm. The group with the greatest exposure (0.55-1.38 ppm) showed significant decreases in lung function over Monday and over the week. Although all employees in this group showed decreases in pulmonary function, acute changes were greater in present cigarette smokers and in subjects who reported respiratory symptoms upon exposure to the epoxy resin system. There was no evidence of permanent loss of lung function in subjects with either the highest or longest exposure.     

Evaluation of alternative methods for establishing safe levels of occupational exposure to vinyl halides

The facts that reduction of occupational vinyl chloride exposures to levels within or below the 0.5-5 ppm range has so far been successful in eliminating vinyl chloride-induced liver angiosarcoma and that humans appear to be less sensitive to the carcinogenic effect of vinyl chloride than rats offered an opportunity to verify or dispute risk assessment extrapolation models used, and proposed, by the U.S. EPA. Safe occupational vinyl chloride exposures were defined as levels associated with an incidence of one angiosarcoma in 100,000 exposed workers, determined from rat bioassay data using default no-threshold (linearized multistage model and benchmark dose approach with linear extrapolation) and threshold (NOEL/LOEL and benchmark dose uncertainty factor approaches) models, and then compared against the likely protective range of 0.5-5 ppm. Safe levels derived using either no-threshold model are equivalent and are two to three orders of magnitude below the 0.5-5 ppm range. Safe levels derived using either threshold model, when applying uncertainty factors which reflect equal or less sensitivity in humans compared to rats, fall within the 0.5-5 ppm range. Similar results were obtained for vinyl bromide and vinyl fluoride. These results undermine the U.S. EPA default assumption of no-threshold for vinyl halides as well as for other DNA-reactive carcinogens while simultaneously supporting the notion that a practical threshold exists. They further suggest that when threshold models are appropriate, the default assumption of greater sensitivity in humans compared to rats should be carefully evaluated.     

Neurobehavioral effects in occupational chemical exposure

Neurotrophic factors, such as nerve growth factor (NGF), in addition to their role in neuronal development, have protective effects on neuronal survival. Intracerebral implantation of cells genetically altered to secrete high levels of NGF is also found to promote neuronal survival in experimental lesioning models of the brain. The range of activity for such biological delivery systems has not yet been well described either spatially or temporally. Therefore, the authors chose to study the local and distant protective effects of an NGF-secreting rat fibroblast cell line implanted in an excitotoxic lesion model of Huntington's disease. They found that preimplantation of NGF-secreting fibroblasts placed within the corpus callosum reduced the maximum cross-sectional area of a subsequent excitotoxic lesion in the ipsilateral striatum by 80% when compared to the effects of a non-NGF-secreting fibroblast graft, and by 83% when compared to excitotoxic lesions in ungrafted animals (p < 0.003). However, NGF-secreting cells placed in the contralateral corpus callosum failed to affect striatal lesion size significantly when compared to contralateral or ipsilateral non-NGF-secreting cell implants. Of note, fibroblasts were clearly visible within the graft site at 7 and 18 days after implantation; however, few cells within the grafts stained positively for NGF peptide or for the messenger ribonucleic acid (mRNA) encoding the transfected NGF gene-construct at either time point. These results show that biological delivery systems for NGF appear to have a profound but local effect on neuronal excitotoxicity, which will necessitate careful neurosurgical placement for maximum effect. Furthermore, the ability of this genetically altered cell line to synthesize NGF mRNA and peptide appears to decrease spontaneously in vivo, a characteristic that will need to be addressed before this method of biological delivery can be utilized as a treatment for chronic degenerative diseases.     

Prophylaxis after occupational exposure to human immunodeficiency virus (HIV)

Reasons for seeking consultation among health care workers due to potential or supposed risk of HIV infection were analyzed. From August 1990 till July 1996 41 health care providers were consulted including: 22 nurses, 1 student of nursing college, 3 midwives, 4 laboratory workers and 7 physicians (surgeons and gynaecologist). Type of exposure to HIV and applying of safety precautions were evaluated in each case. In 10 cases the offer of postexposure prophylaxis with zidovudine was accepted (6 nurses, 1 student of nursing college, 3 surgeons). Exposure to HIV was described as: needlestick immediately after it was used in a HIV/AIDS patient, injury with a surgical needle while operating on an HIV infected blood. In the remaining cases the fear of HIV infection was due to work without protective gloves (nurses, laboratory workers), performing surgery on HIV (+) patient, (surgeons, nurses) or short-time contact of HIV infected blood with undamaged skin (nurses). Following conclusions can be drawn from our study: 1. Health care workers undertake safety precautions only when they are informed about HIV seropositivity of the patient. 2. Patients whose HIV serologic status is not known are considered not to create health risk for medical staff. 3. The level of knowledge of health care workers about risk of acquiring HIV infection, lack of risk and ways of diminishing the risk is poor. 4. None of followed health care workers was HIV-seropositive after occupational exposure to HIV.     

Cancer risk from occupational and environmental exposure to polycyclic aromatic hydrocarbons

Epidemiologic evidence on the relationship between polycyclic aromatic hydrocarbons (PAH) and cancer is reviewed. High occupational exposure to PAHs occurs in several industries and occupations. Covered here are aluminum production, coal gasification, coke production, iron and steel foundries, tar distillation, shale oil extraction, wood impregnation, roofing, road paving, carbon black production, carbon electrode production, chimney sweeping, and calcium carbide production. In addition, workers exposed to diesel engine exhaust in the transport industry and in related occupations are exposed to PAHs and nitro-PAHs. Heavy exposure to PAHs entails a substantial risk of lung, skin, and bladder cancer, which is not likely to be due to other carcinogenic exposures present in the same industries. The lung seems to be the major target organ of PAH carcinogenicity and increased risk is present in most of the industries and occupations listed above. An increased risk of skin cancer follows high dermal exposure. An increase in bladder cancer risk is found mainly in industries with high exposure to PAHs from coal tars and pitches. Increased risks have been reported for other organs, namely the larynx and the kidney; the available evidence, however, is inconclusive. The results of studies addressing environmental PAH exposure are consistent with these conclusions.