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PubMedDate not supplied

[Berylliosis in Italy: a case of "sarcoidosis" under the threshold limit value].

BACKGROUND: Berylliosis is caused by a chronic immune reaction to beryllium; in Italy the first case of beryllium exposure-related disease was described in 1935 by Fabroni-Marradi and two additional cases of beryllium disease were subsequently described by Ambrosi and co-workers in 1968. No case has since been recognized using the standardized criteria including immunological testing. OBJECTIVES: To describe a case report of clinically significant berylliosis that occurred in a man exposed to beryllium for ten years in the workplace at concentrations below the permitted threshold limit value. METHODS: The man complained of dyspnoea, dry cough, weakness and weight loss for the past year and was at first diagnosed as suffering from sarcoidosis because of increased angiotensin converting enzyme levels, alteration of hepatic and renal functional indexes, the presence of diffused reticulo-nodular lung abnormalities with high resolution computed tomography that also showed enlarged mediastinal lymph nodes, abnormal lung physiology with reduced diffusion capacity and a bronchial biopsy showing granulomatous lesions. Because of the occupational history immunological testing and high resolution HLA class II typing were performed. RESULTS: The high response to beryllium in the lymphocytes proliferation test and the HLA typing which revealed the presence of the two susceptibility markers HLA-DPGlu69 and HLA-DRPhe47 led to a diagnosis of berylliosis. CONCLUSIONS: The importance is stressed of suspecting a diagnosis of berylliosis in the proper occupational contexts and encouraging the use of immunological tests for diagnosis, and also the need for critical revision of the permitted threshold limit values.

Adult↗
PubMed1997

Metal fume fever: characterization of clinical and plasma IL-6 responses in controlled human exposures to zinc oxide fume at and below the threshold limit value.

Results from animal and preliminary human exposure studies have called into question whether the 5 mg/m3 8-hour time-weighted average threshold limit value (TLV) for zinc oxide fume is sufficient to protect workers against metal fume fever. The objectives of this study were to determine the clinical effects of exposures to low concentrations of zinc oxide and to ascertain whether these exposures elevated circulating levels of specific cytokines, which could account for the symptoms of the metal fume fever syndrome. Thirteen resting naive subjects inhaled, on separate days, air and 2.5 and 5 mg/m3 of furnace-generated zinc oxide fume for 2 hours. Subjects recorded symptoms and temperature and had blood drawn before and after each exposure. The mean (+/- SE) maximum rise in oral temperature at 6 to 12 hours after exposure was 1.4 +/- 0.3 degrees F after 5 mg/m3, compared with 0.6 +/- 0.5 degrees F after air exposure (P < 0.05). Mean temperature was also elevated after exposure to 2.5 mg/m3 zinc oxide (1.2 +/- 0.3 degrees F). In a parallel fashion, plasma levels of interleukin 6 (IL-6), a pyrogen, were significantly elevated after exposure to 5 mg/m3 zinc oxide. Mean IL-6 values (pg/mL) at pre-exposure and at 3 and 6 hours post-exposure were 1.9 (+/- 0.6), 2.8 (+/- 0.7), and 2.9 (+/- 0.6), respectively, on the air day and 1.6 (+/- 0.6), 4.4 (+/- 1.2), and 6.4 (+/- 1.1) on the 5 mg/m3 zinc oxide day. Zinc oxide exposure did not significantly affect plasma levels of tumor necrosis factor. Total symptom scores peaked 9 hours after the 5 mg/m3 zinc oxide exposure. Myalgias, cough, and fatigue were the predominant symptoms reported. Inhalation of zinc oxide for 2 hours at the current TLV of 5 mg/m3 produces fever and symptoms along with elevation in plasma IL-6 levels.

Adult↗
PubMed1995

The origin and development of the asbestos Threshold Limit Value: scientific indifference and corporate influence.

Several recent articles have critiqued the process employed by the American Conference of Governmental Industrial Hygienists in determining Threshold Limit Values. Criticisms have included inadequate data collection, inadequate research, excessive corporate influence, and slow response to informational changes. In this article, the authors address the historical development of the American Conference of Governmental Industrial Hygienists' asbestos exposure guideline. They demonstrate that the proposed guideline was known to be inadequate when it was first proposed, was severely criticized between 1946 and 1968, but nonetheless was promulgated annually and remained unchanged 1971.

Asbestos↗
PubMed1995

Toluene diisocyanate induction of airway hyperresponsiveness at the threshold limit value (10 ppb) in rabbits.

Induction of acute lung injury and the development of airway hyperresponsiveness (AHR) by toluene diisocyanate (TDI) exposure was studied in a new rabbit model of occupational lung diseases. TDI in the range of the threshold limit value (TLV) of 10 ppb, as well as at 5 and 30 ppb, administered four times over a period of 1 h to three groups of eight rabbits, did not significantly alter airway resistance (RI), dynamic elastance (Edyn), slope of inspiratory pressure generation (delta Pes/tI), arterial pressure (Pa) or arterial blood gas tensions (PaO2, PaCO2). Airway responsiveness (AR) to aerosols of 2% acetylcholine (ACH) was measured before and after each TDI exposure. After TDI inhalation of 10 ppb over 4 h, the amplitude of the ACH-induced airway constrictor response indicated by the changes in Edyn rose significantly to almost twice the control response value (p < 0.005). Similar changes in the amplitude of RI and in the slope of delta Pes/tI were obtained. After inhalation of 5 ppb TDI, no changes in airway reactivity were observed. The responses of respiratory mechanical parameters to ACH rose to three to four times the control responses after exposure to 30 ppb TDI. In a control group of eight animals not undergoing TDI exposure, no significant changes of respiratory responses were obtained after inhalation of 0.2% ACH for 1 min. In summary, TDI atmospheres in the range of TLV increased AR to ACH within 4 h of exposure in this rabbit model. This augmented AR may indicate an increased risk for the development of isocyanate-induced obstructive lung diseases.

Acetylcholine↗
PubMed1993

Threshold limit values, permissible exposure limits, and feasibility: the bases for exposure limits in the United States.

The development of exposure limits in the United States has always relied heavily upon the threshold limit values (TLVs) developed by the American Conference of Governmental Industrial Hygienists (ACGIH). In fact, the TLVs were adopted as official exposure limits by the Occupational Safety and Health Administration (OSHA) in 1972 and 1989. Given the continuing importance of the ACGIH limits, this paper compares the basis of the TLVs with that employed by OSHA de novo in its 12 new permissible exposure limits (PELs). Using benzene as an example, it is shown that OSHA's new PELs have been established following a rigorous assessment of the inherent risks and the feasibility of instituting the limit. The TLVs, on the other hand, have been developed by ad hoc procedures and appear to have traditionally reflected levels thought to be achievable at the time. However, this might be changing. Analysis of the historical reductions of TLVs, for 27 substances on the 1991-1992 list of intended changes, indicates smaller reductions in the past (median reduction of 2.0-2.5-fold between 1946 and 1988) compared to those currently being observed (median reduction of 7.5-fold between 1989 and 1991). Further analysis suggests a more aggressive policy of the ACGIH regarding TLVs for carcinogens but not for substances that produce effects other than cancer. Regardless of whether the basis of the TLVs has changed recently, it would take a relatively long time for the impact of any change to be felt, since the median age of the 1991-1992 TLVs is 16.5 years, and 75% of these limits are more than 10 years old. The implications of OSHA's continued reliance on the TLVs as a means of updating its PELs are discussed, and four alternatives are presented to the ACGIH regarding the future of its activities related to exposure limits. It is concluded that new mechanisms are needed for OSHA to update its PELs in a timely fashion so that the TLVs will not be adopted by default in the future.

Air Pollutants, Occupational↗
PubMed1977

Proposed biological threshold limit values for industrial exposure to trichloroethylene vapor.

A model was used for the simulation of the pharmacokinetics of inhaled trichloroethylene (TRI) vapor. Computed data of TRI in alveolar air and of trichloroacetic acid (TCA) and trichloroethanol (TCE) in blood and urine agreed satisfactorily with experimental results obtained by various authors. Biological threshold limit values were calculated for subjects exposed at rest to a steady concentration of 100 ppm of TRI in ambient air, between 0800 and 1200 and between 1300 and 1700, five days week during the whole year. The Monday to Friday range of values for urinary excretion (243--322 mg of TCA/24 h and 288--429 mg of TCE/24 h) roughly corresponded to the findings of several surveys among TRI workers in industry. The hypnotic effect of TCE and/or TRI during steady or fluctuating industrial TRI exposure was discussed with the aid of the model.

Chloral Hydrate↗
PubMed1994

Sensory irritation and pulmonary irritation of n-methyl ketones: receptor activation mechanisms and relationships with threshold limit values.

Activation of the trigeminal nerve endings in eyes and nose, termed sensory irritation, was determined from the reflexively induced decrease in respiratory rate in mice for methyl propyl ketone, methyl butyl ketone, methyl amyl ketone and methyl hexyl ketone. The relationship between exposure concentration and the decrease in respiratory rate followed Michaelis-Menten equations. Two estimates of each agonist-receptor dissociation constant were obtained, one from the Michaelis-Menten equation and one from the threshold (RD-0) of the log concentration-effect curve. The values were equal and thus one receptor type could account for the activation process. The hydrophobic properties of the receptor biophase were found to approach that of the internal part of the bilayer membrane. It therefore follows that the receptor-air partition coefficients increase with the size of the ketones, thus accounting for the observed increase in potency. Estimates of Threshold Limit Values (TLV) were obtained and compared with established values. Close agreements were found for methyl propyl ketone and methyl amyl ketone, but not for methyl butyl ketone, where the neurotoxic effect constituted a more sensitive endpoint than sensory irritation.

Administration, Inhalation↗
PubMed1991

Chromated steel and contact allergy. Recommendation concerning a "threshold limit value" for the release of hexavalent chromium.

Steel surfaces can be treated with zinc and chromates to prevent the steel from rusting. Cases of allergic contact dermatitis due to the release of hexavalent chromium (Cr64) from chromated surfaces have been reported. The main purpose of the present study was to develop a simple procedure for the determination of leachable Cr64 that could be used in industrial applications to check the quality of chromated products and to establish a "threshold limit value" for such products. Occlusive tests were performed in chromate-sensitive patients using chromated discs, and discs representing a release of 0.6 microgram/cm2 or more elicited positive results in all patients tested. It was proposed that the mean release of Cr64 from chromated parts should not exceed 0.3 microgram/cm2. Approximately 1 out of 4 yellow chromated parts, collected from a chromating plant and a car assembly plant, gave values above this limit. Today, several tests are performed to evaluate the technical quality of the chromate layers. It is suggested that the present method should be added to the test program in order to reduce the risk of causing chromate allergy.

Chromates↗