Biological effects of trinitrotoluene from exposure below the threshold limit value.

Statistically significant rises in serum glutamic oxalacetic transaminase and lactic dehydrogenase determinations occurred at exposures to TNT of 0.8 mg/m3 and persisted at exposures of 0.6 mg/m3. Based on these findings, the adequacy of the current threshold limit value for TNT (1.5 mg/m3) is questioned.     

Psychological performance of workers with blood-lead concentration below the current threshold limit value

Summary The effects of lead exposure on psychological test performance and subjective feelings of well-being were investigated in 40 exposed workers whose PbB levels had never exceeded 60 g/100 ml and in 20 controls matched for sex, age and educational level. The exposed workers were divided into two groups of 20, with recent PbB levels in the range 45–60 g/100 ml or below 35 g/100 ml. The group of workers with the higher PbB levels showed significantly poorer performance and reported more physical symptoms than the other two groups. These differences were unrelated to socio-demographic and personality characteristics. A principal component analysis suggested that the poorer performance was mainly due to an impairment of general functioning and only to some extent to a deterioration in specific functions, such as verbal reasoning and abstraction. Higher lead concentrations were correlated with poorer performance and a higher number of physical complaints. These results indicate that in exposed workers the threshold for impaired performance lies below the blood-lead concentration of 60 g/100 ml, which is the current threshold limit value (TLV).This study was supported by the Consiglio Nazionale delle Ricerche (CNR, Roma), Gruppo Nazionale Scienze del Comportamento (Grant no. 81.00083.04 and no. 82.02117.04)     

Formate in serum and urine after controlled methanol exposure at the threshold limit value.

Methanol will be present as a new air pollutant when methanol-powered vehicles are introduced in the United States. Little is known about the effect of low-dose methanol exposure. It is controversial whether or not formate, the main metabolite responsible for methanol's acute toxicity, is a sensitive biological marker of toxicity or exposure. We studied the effect of a 4-hr exposure at rest to 200 ppm of methanol vapors on endogenous serum formate and on urinary formic acid excretion. A randomized, double-blind study of human exposure to a constant concentration of methanol was performed in a whole-body exposure chamber. Twenty-six healthy volunteers, each serving as his or her own control, participated in sham and methanol exposures. Urine (at 0, 4, 8 hr) and serum specimens (15 time points over 8 hr) collected before, during, and after the exposure were measured for formate. We found no significant differences in serum formate concentration between exposure and control conditions either at any time point or for area under the curve. Mean concentrations at the end of the exposure were: exposed 14.28 +/- 8.90 mg/l and control 12.68 +/- 6.43 mg/l. A slight, but nonsignificant (p = 0.08), increase in urine formate excretion rate was found at 4 hr (exposed 2.17 +/- 1.69 mg/4 hr and control 1.67 +/- 1.02 mg/4 hr). Age, sex, folic acid level, and smoking were not significant covariates. At 200 ppm, methanol exposure does not contribute substantially to endogenous formate quantities. Serum and urine formate determinations are not sensitive biological markers of methanol exposure at the threshold limit value.     

Surveillance of workers exposed to mercury vapour:validation of a previously proposed biological threshold limit value for mercury concentration in urine

A cross-sectional epidemiological study was carried out among subjects exposed to mercury (Hg) vapour, ie, a group of 131 male workers (mean age: 30.9 yr; average duration of exposure, 4.8 yr) and a group of 54 female workers (mean age, 29.9 yr; average duration of exposure 7 yr). The results were compared with those obtained in well-matched control groups comprising 114 and 48 male and female workers, respectively. The intensity of current Hg vapour exposure was rather moderate as reflected by the levels of mercury in urine (HgU) (mean and 95th percentile: males 52 and 147 micrograms/g creatinine; females 37 and 63 micrograms/g creatinine) and of mercury in blood (mean and 95th percentile: males 1.4 and 3.7 micrograms/dl; females 0.9 and 1.4 microgram/dl). Several symptoms mainly related to the central nervous system (memory disturbances, depressive feelings, fatigue, irritability) were more prevalent in the Hg-exposed subjects. They were, however, not related to exposure parameters. In both male and female Hg-exposed workers no significant disturbances were found in short-term memory (audioverbal), simple reaction time (visual), critical flicker fusion, and colour discrimination ability. Only slight renal tubular effects were detected in Hg-exposed males and females, ie, an increased urinary beta-galactosidase activity and an increased urinary excretion of retinol-binding protein. The prevalence of these preclinical renal effects was more related to the current exposure intensity (HgU) than to the duration of exposure and was detected mainly when HgU exceeds 50 micrograms/g creatinine. Changes in hand tremor spectrum recorded with an accelerometer were found in the Hg-exposed males only. The prevalence of abnormal values for some hand tremor parameters (total velocity and total displacement in the 2-50-Hz band) was mainly increased in male workers exposed for more than 10 yr. Unlike the renal tubular effects, the preclinical signs of tremor were more related to the integrated exposure than to the current exposure. Since the female workers, who have been exposed to Hg vapour levels usually insufficient to increase their HgU levels above 50 micrograms/g creatinine, did not exhibit any change in hand tremor pattern, the results of the present study tend to validate our previously proposed biological threshold limit value of a HgU of 50 micrograms/g creatinine for workers chronically exposed to mercury vapour.     

The case for re-evaluating the upper limit value for selenium in drinking water in Europe

Selenium is an essential trace element for life, which can be toxic for humans when intakes reach a certain amount. Therefore, since the margin between healthy intake and toxic intake is narrow, the selenium concentration of tap water is a parameter that must be monitored because of its potential for increased intake. The present work gives an overview of the different approaches used to calculate safe limits for selenium. As recommended by WHO, the guidelines for drinking water form the basis of national legislated standards for drinking water. Before setting a maximum acceptable level in drinking water, it is necessary to take into account the total intake of selenium in both food and beverage. The limit value of 10 mg l^-1 for drinking water laid down in the European regulations for all countries should be adapted depending on geographic area, as previously recommended by WHO.     

Estimation of the general threshold limit values for dust

In 1997 the German MAK Commission set new general threshold limit values for dust. The procedure has recently been assessed (McLaughlin et al. 2001). One of the points raised was the use of inappropriate statistical methods. We want to address this point to a greater extent by discussing several alternatives implied by the already established threshold models, and we present results from a new approach that has been refined in the meantime: the use of the additive isotonic model. The underlined assumption of monotonicity regarding the dose-response relationship has been extensively investigated. One very flexible model, based on smoothing splines, shows in some of the samples a decline in the risk over a certain range of the exposure compared to the risk at baseline. Another approach with fractional polynomials and segmented regression lines shows that this result can be explained by chance. These methods show an increasing risk with increasing exposure. Additionally, permutation tests are used to prove the trend within the isotonic framework. The results from the additive isotonic model confirm previous assessments of the general threshold limit value.     

Pulmonary clearance and lesions in rats after a single inhalation of ultrafine metallic nickel at dose levels comparable to the threshold limit value.

This study aimed to (1) determine the deposition and clearance rates of ultrafine metallic nickel (Uf-Ni) in rats after a 5 hours single inhalation exposure, and (2) to histopathologically examine the pulmonary lesions induced at dose levels comparable to the Occupational Exposure Limit recommended in Japan (OEL). The exposure concentrations of Uf-Ni for the 3 groups were 0.15 (Low), 1.14 (Medium), and 2.54 (High) mg/m3. Five rats/group were sacrificed at 0 h and 1, 3, 7, 14, and 21 days post exposure. The amount of Ni in the lung accumulated dose-dependently. The half-times for Ni in the lung were estimated as 32 days on average, and were similar to each other regardless of the initial dosage. The histopathologically observed pulmonary lesions induced by a single inhalation of Uf-Ni were, (1) a significant increase in lung weight in the High and Medium groups with time, (2) accumulation of foamy alveolar macrophages (AM), (3) degenerated AM indicating alveolar lipoproteinosis which was aggravated for up to 4 weeks in the High group and (4) acute calcification of the degenerated AM was remarkable. The present results suggest that even a single inhalation of Uf-Ni induces potency of lung lesions at dose levels comparable to the OEL (1 mg/m3 as Ni), or the TWA of ACGIH (1.5 mg/m3 for elemental/metal).     

Aortic intimal injury in rabbits. An evaluation of a threshold limit.

Sixty-one rabbits were exposed to carbon monoxide, and aortae were then examined by light microscopy and transmission and scanning electron microscopy. The CO concentration in ambient air and the exposure time were varied to estimate the threshold limit for CO-induced focal intimal edema. A significantly higher incidence (P less than .0001) of focal intimal changes was present in rabbits exposed to 180 ppm of CO for four hours or more than in rabbits given a shorter or weaker exposure. The present study, as well as recent reports on the effect of low-level CO exposure on the cardiovascular system, suggests that the CO content in tobacco smoke and in heavily polluted atmospheric air may be deleterious to the arterial wall and enhance atherogenesis. A reevaluation of the recommended threshold limit for industrial CO exposure is proposed.     

Hypertrophic cervical spine pachymeningitis due to sarcoidosis: a case report

Hypertrophic pachymeningitis (HP) is a chronic, progressive diffuse inflammatory condition that leads to thickening of the dura mater and can be idiopathic or associated with sarcoidosis among other disorders. In this case report, we present a rare case of cervical spine HP in a 29-year-old woman in the post-partum period, who had a history of pituitary adenoma and juvenile rheumatoid arthritis. Magnetic resonance imaging (MRI) of the spine revealed a soft tissue mass and moderate cord compression. The patient underwent C3-C7 laminectomy. Pathological analysis of the cervical epidural mass demonstrated a reactive inflammatory cell process. Recurrence of symptoms and worsening of pachymeningitis on imaging studies warranted further work-up which revealed mediastinal/hilar lymphadenopathy. Transbronchial biopsy revealed non-caseating granulomatous disease consistent with sarcoidosis. The patient was started on oral steroids and eventually methotrexate with significant clinical and radiographic improvement. Follow-up imaging studies showed minimal dural thickening in the thoracic spine and eventually complete resolution. HP should be considered in a patient with spinal cord compression, myelopathy, and radicular pain of unclear etiology, and sarcoidosis should be considered in idiopathic cases.