Residual neurobehavioural effects associated with chronic exposure to mercury vapour.

To find the residual effects of long term exposure to mercury vapour, neurobehavioural tests were given to ex-mercury miners about 18 years after the end of mercury exposure. Seventy six male ex-mercury miners who had been exposed to high concentrations of mercury vapour (over 1.0 mg/m3) and with a history of mercury intoxication were compared with controls matched for age (within 3 years), sex, and education. Although the extent of the workers' symptoms caused by mercury poisoning, termed erethismus merculialis, decreased considerably after the end of exposure, matched paired comparison showed that performances of motor coordination, simple reaction time, and short term memory had deteriorated significantly in the exposed group. Multiple linear regression analysis of exposure variables with neurological examination measures showed positive correlations between poorer neurological performance and variables related to mercury exposure. Thus the duration of exposure correlated with poorer performance of hand-eye coordination, tapping, and a colour card reading test. Job categories classified by exposure to mercury also had a significant negative correlation with these performances. The period of years after the end of exposure had a significant correlation with better performance of reaction time and digit span. On the other hand, the history of intoxication itself had no significant correlation with any of the current neurobehavioural performances. These results suggest that there are slight but persistent effects on neurobehavioural function, especially on motor coordination, among mercury miners even more than 10 years after the end of exposure.     

Low-level hydrocarbon solvent exposure and neurobehavioural effects

Studies of workers exposed to hydrocarbon solvents are reviewed in order to address the question, 'Does long-term human exposure to hydrocarbon solvents at concentrations around occupational exposure limits result in clinically important neurobehavioural effects?' Studies selected evaluated exposure-response (E-R) trends with some control of potential confounders. Tests of neurobehavioural performance were classified into specific functional categories, within those of cognitive, psychomotor and sensory functions to increase specificity and power to detect patterns of effect. The weight-of-evidence was evaluated with respect to criteria for determining causality. The temporality criterion was met as latency was adequate for the occurrence of chronic effects. There were few significant associations, and when present, were consistently weak even in the most-exposed workers. Exposure response showed no consistent or significant pattern for any tests of functional mortality. The weight of evidence suggests that exposure to hydrocarbon solvents at current limits does not appear to cause adverse neurobehavioural effects.     

Local exhaust ventilation and exposure to nitrous oxide in ambulances

Summary Under extreme conditions, ambulance attendants and drivers could be exposed to nitrous oxide administered to transported patients in concentrations causing acute effects. Special arrangements are necessary to prevent such exposure, which is influenced by travelling speed, local exhaust ventilation and the use of an excess gas transfer tube evacuating expired air and overflow gas from the face mask to the outside. The separate eliminative effects of travelling speed and local exhaust varied considerably with the experimental conditions. The excess gas transfer tube reduced the levels of nitrous oxide in the air by 86 to 97% inside the ambulance at different experimental conditions. The combination of excess gas transfer tube and local exhaust resulted in a relatively constant reduction of the airborne nitrous oxide levels by about 98% when the ambulance was at a standstill and 99% when it was running.     

Local exhaust ventilation and exposure to nitrous oxide in ambulances

Under extreme conditions, ambulance attendants and drivers could be exposed to nitrous oxide administered to transported patients in concentrations causing acute effects. Special arrangements are necessary to prevent such exposure, which is influenced by travelling speed, local exhaust ventilation and the use of an excess gas transfer tube evacuating expired air and overflow gas from the face mask to the outside. The separate eliminative effects of travelling speed and local exhaust varied considerably with the experimental conditions. The excess gas transfer tube reduced the levels of nitrous oxide in the air by 86 to 97% inside the ambulance at different experimental conditions. The combination of excess gas transfer tube and local exhaust resulted in a relatively constant reduction of the airborne nitrous oxide levels by about 98% when the ambulance was at a standstill and 99% when it was running.     

Occupational exposure to sevoflurane and nitrous oxide in operating room personnel

 Object: To quantify the exposure of operating room personnel to sevoflurane and nitrous oxide. Design: Prospective study at a university hospital. Methods: In 25 patients undergoing elective surgical procedures, anaesthesia was induced with thiopentone/etomidate, vecuronium and fentanyl and maintained with fentanyl, sevoflurane in 35% oxygen and 65% nitrous oxide (N₂O). Occupational exposure to sevoflurane and N₂O was measured in the breathing zone of one representative of each of three personnel groups (anaesthetist, surgeon, auxiliary nurse) by means of a direct reading instrument using photoacoustic infrared spectrometry. Results: The mean trace concentrations of sevoflurane for the single anaesthetic procedures exceeded the 0.5 ppm level in more than 50% of the measurements. The 2 ppm level was not exceeded in the case of the anaesthetist and the surgeon, but was exceeded in 16% of the measurements for the auxiliary nurse. The level of 25 ppm N₂O were exceeded in 28% of the measurements for the anaesthetist and in 16% of these for the surgeon and for the auxiliary nurse. Conclusions: To keep exposure low, sevoflurane and N₂O were used in a modern working environment: a low-leakage anaesthesia machine, high room ventilation rates, scavenging system, no intermittent mask ventilation, low to medium concentrations of sevoflurane, and strict control of the cuff pressure. Nevertheless, exposure could not be kept under NIOSH threshold values in all cases. Received: 21 December 1995/Accepted: 2 April 1996     

The effects of nitrous oxide after exposure during middle and late gestation

Recent evidence has indicated that the anesthetic gas nitrous oxide (N2O) is teratogenic to rats if exposed during the organogenesis phase of gestation. Little is known, however, of the anatomical or functional consequences of exposures occurring later in gestation when the brain is developing. Timed pregnant Sprague-Dawley rats were exposed to 75% N2O/25% O2 using one of the following protocols: 24 hr exposures on gestational days 11-15 or 16-20; or 8 hr exposures on gestational days 9-13, 11-15, 14-15 or day 15 only. Both 24 hr exposure protocols significantly reduced fetal and maternal body weight, an effect not observed after the 8 hr exposures. No N2O exposure resulted in gross morphological or skeletal changes. Likewise, no significant effects on total protein and DNA levels in fetal liver and brain tissues could be found subsequent to 24 hr exposures on days 16-20; or on one, three or six days following an 8 hr exposure on day 15. Evaluations of postnatal growth and neurological development in pups prenatally exposed for 8 hr on days 14 and 15 revealed two noteworthy effects. Their rate of growth in body weight was greater with respect to controls between the ages of 14 and 21 days, especially in the males. Also, reflex suspension was reduced, significantly so in the females. In conclusion, unlike 24 hr exposures, multiple 8 hr exposures to nitrous oxide during the middle to late stages of gestation did not produce effects detectable with standard teratological measures. Subtle differences in growth rate and reflex suspension, however, indicated that normal development had been interrupted, but its clear distinction as a lasting effect requires additional measures of function.     

The effects of exposure to aluminium on neurobehavioural function and dopaminergic metabolism

A study was conducted to evaluate the effects of exposure to aluminium (Al) on neurobehavioural function and dopaminergic metabolism among 33 exposed workers compared to 40 controls. The parameters measured included concentrations of Al in air, serum Al and urine Al. WHO Neurobehavioural Core Test Battery was used to measure the neurobehavioural functions. Homovanillic acid (HVA) and vanillymandellic acid (VMA), two end products of catecholamine metabolism were measured using high-pressure liquid chromatography (HPLC). Determinations of Al in serum and urine were carried out using precolumn lumogallion reaction HPLC technique. The geometric mean of the airborne concentration of inhalable Al dust was 1.90 mg/m3 (range 0.62-8.24 mg/m³). The mean concentration of Al in urine was significantly higher in the exposed workers than the controls (12.25 ± 6.04 vs 5.78 ± 3.10 ug/l), but no statistical difference was observed for serum Al (1.68 ± 0.63 vs 1.31 ± 0.40 mug/l); suggesting that urinary Al is a better biomarker for Al exposure. The neurobehavioural evaluation showed that there were significant differences for Santa Ana tests, digit symbol and Benton test, implying that the manual dexterity, eye-hand coordination and memory were poorer in the Al-exposed workers. The data also showed that both of the catecholamine metabolites were higher in the exposed group, especially urinary VMA (p < 0.01). These data reflect that exposure to Al could interfere with the dopaminergic metabolism and neurocognitive function.     

Occupational exposure of midwives to nitrous oxide on delivery suites

Aims: To compare environmental and biological monitoring of midwives for nitrous oxide in a delivery suite environment.     

Proposal for single and mixture biological exposure limits for sevoflurane and nitrous oxide at low occupational exposure levels

OBJECTIVES: Assessment of individual exposures to sevoflurane plus nitrous oxide (N(2)O) by biological monitoring of unmodified analytes in post-shift urine of exposed personnel. METHODS: Anaesthetics in urine and breathing area were monitored in 124 subjects in 11 operating theatres. Passive samplers were collected after 2.5-7 h of exposure, at the same time as post-shift urinary samples, to evaluate the individual time-weighted average (TWA) exposures to sevoflurane and N(2)O. A static headspace sampler coupled with a gas chromatograph mass spectrometer was used for analytical determinations (sensitivity sufficient to reveal biological/environmental exposures of 0.1 microg/l(urine) and 50 ppb for sevoflurane, and 1 microg/l(urine) and 80 ppb for N(2)O). RESULTS: Median (range) post-shift urinary and environmental values were 1.2 microg/l(urine) (0.1-5.0) and 0.4 ppm (0.05-3.0) for sevoflurane ( n=107) and 10.9 microg/l(urine) (0.5-74.9) and 8.6 ppm (0.2-123.4) for N(2)O ( n=121) (all low-exposure range). At log-log regression, urinary levels closely correlated with environmental data (sevoflurane, r(2)=0.7538; N(2)O, r(2)=0.8749). Biological equivalent limits (BELs) based on National Institute for Occupational Safety and Health (NIOSH) TWA exposure limits, calculated as means of regression slope and y-intercept, were 3.6 microg/l(urine) for sevoflurane (corresponding to 2 ppm) and 22.3 microg/l(urine) for N(2)O (corresponding to 25 ppm). Individual "mixture BELs", which we calculated by applying the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value (TLV) mix formula to biomarker values and using the obtained NIOSH-based BELs as a reference, closely correlated with mixture TLVs (rho=0.816, Lin's concordance test). CONCLUSIONS. We propose urinary sevoflurane as a new, specific, internal dose biomarker for routine biological monitoring of personal exposures among operating-theatre personnel, and use of reliable "mixture BELs" to provide safer levels of internal exposure for workers exposed to mixtures of sevoflurane and N(2)O, and conceivably also to other mixtures of toxicants with possible additive effects.     

Biological monitoring of nitrous oxide exposure in surgical areas

Exposure to nitrous oxide in surgical theaters was evaluated for duration, numbers, and types of surgical procedures. The concentration of the gas in the air was 92-444 ppm. Before and after the surgical sessions, samples of urine and expired air were collected from surgical theater personnel for gas determination. Nitrous oxide concentrations in urine and in expired air showed a good correlation with gas concentration in the air (r = 0.760 and r = 0.921, respectively). Moreover, a good correlation (r = 0.823) between gas concentration in urine and that in expired air was also found. A biological threshold limit value (TLV) of 20.6 micrograms/liter for urine and of 29.6 ppm for expired air was calculated, based on the limit of 50 ppm in the air proposed by the American Conference of Governmental Industrial Hygienists (ACGIH). Other biological TLVs corresponding to higher proposed limits (200 and 500 ppm) were also calculated.     

Study of the neurobehavioural toxicity of styrene at low levels of exposure

Summary Thirty workers in a dockyard exposed to concentrations of styrene lower than the TLV-TWA of 50 ppm and 30 control workers not subject to exposure but employed by the same company were subjected to three psychometric tests on one Monday morning and evening. The results were usually better in the evening than in the morning in both groups, which proves the lack of acute intoxication at the end of the day at this level of exposure. On the other hand, all of the tests conducted on the exposed subjects are significantly less good than those on the controls. The results suggest the existence of minor but significant organic mental disorders in the subjects exposed to a mean dose of 30 Wpm in this study. These results are inconsistent with those of several recent studies. The advisability of lowering the TLV of 50 Wpm in discussed.     

Behavioral toxicity of nitrous oxide in rats following prenatal exposure

Nitrous oxide (N2O) exposure has been associated with neurotoxicity, especially peripheral neuropathy, in both humans and animals. The effects of this anesthetic gas on the central nervous system (CNS) and spontaneous behavior, however, have yet to be delineated. Timed-pregnant Sprague-Dawley rats were exposed to 75% N2O/25% O2 on gestational days 14 and 15 or day 15 only for eight hours per day. The offspring were tested at one and five months of age; their spontaneous behavior in a novel environment was recorded in the residential maze and using time-lapse photography. The results indicated that in utero exposure to N2O permanently altered the spontaneous motor output of the CNS. This effect was most prominent in 5 month old animals, and females were affected more than males. Exposures on gestational days 14 and 15 produced an effect that was not only greater but also qualitatively different than that produced by exposure on day 15 only. The two-day exposure induced hyperactivity in both sexes, whereas the one-day exposure induced hyperactivity in the males and slight hypoactivity in the females. These behavioral changes were not accompanied by physical abnormalities but nonetheless were lasting effects in need of further consideration.     

Investigation of dose related neurobehavioural effects in paintmakers exposed to low levels of solvents.

A cross sectional study was carried out to compare 110 paintmakers exposed to solvents with 110 age matched controls for outcome measures designed to assess cognitive performance and mental health. Hygiene data available for the paintmakers allowed the development of individual indices of solvent exposure and the analyses of health effects in relation to both duration and intensity of exposure. No effects on cognitive functioning or mental health were found in the paintmakers. For most of their period of employment the exposure of the paintmakers had been below current occupational exposure limits. The results are therefore interpreted as providing support for the view that long term exposure at or below current compliance levels does not result in damage to the central nervous system.     

Neuropsychiatric effects of low exposure to styrene

Workers exposed to styrene concentrations of about 50 mg/m3 at a plant manufacturing reinforced polyester boats were examined for neuropsychiatric symptoms both in close connection with exposure and also seven months after exposure had ceased. Physical workload is important for the uptake of styrene and was about 50 W at this plant. On the first occasion, after one week with no exposure, the workers reported a high frequency of neuropsychiatric symptoms such as fatigue, irritation, and forgetfulness whereas seven months later the frequency of these symptoms was low. These observations indicate that exposure to styrene at about 50 mg/m3 may induce reversible neuraesthenic symptoms. Even the relatively low Swedish standard (110 mg/m3 = 25 ppm) may, therefore, need revising.     

Short-term and long-term physical effects of exposure to CS spray

CS gas (2-chlorobenzylidene malonitrile) is widely used in an incapacitant spray that causes intense lacrimation, blepharospasm and burning sensations in the throat and nose. Questions have been raised about its safety. We obtained information on short-term and long-term symptoms, and performed ear, nose and throat examinations and respirometry at 8-10 months, in 34 young adults who had been exposed to CS spray in a confined space during a confrontation with police. The group was subdivided into those who had been sprayed directly on the face (n=10) and those exposed indirectly. At one hour, all but 2 individuals still had symptoms; respiratory and oral symptoms were significantly more prevalent in the directly exposed group. At one month, only oral symptoms were significantly more prevalent. At 8-10 months, symptoms were still reported but there were no differences between the groups and clinical examinations revealed no specific abnormalities. There was no convincing evidence of long-term physical sequelae from exposure to CS spray.     

Neuropsychiatric effects of low exposure to styrene.

Workers exposed to styrene concentrations of about 50 mg/m3 at a plant manufacturing reinforced polyester boats were examined for neuropsychiatric symptoms both in close connection with exposure and also seven months after exposure had ceased. Physical workload is important for the uptake of styrene and was about 50 W at this plant. On the first occasion, after one week with no exposure, the workers reported a high frequency of neuropsychiatric symptoms such as fatigue, irritation, and forgetfulness whereas seven months later the frequency of these symptoms was low. These observations indicate that exposure to styrene at about 50 mg/m3 may induce reversible neuraesthenic symptoms. Even the relatively low Swedish standard (110 mg/m3 = 25 ppm) may, therefore, need revising.     

Occupational exposure to nitrous oxide - the role of scavenging and ventilation systems in reducing the exposure level in operating rooms

OBJECTIVES: The aim of this study was to assess the level of occupational exposure to nitrous oxide (N(2)O) in operating rooms (ORs), as related to different ventilation and scavenging systems used to remove waste anaesthetic gases from the work environment. METHODS: The monitoring of N(2)O in the air covered 35 ORs in 10 hospitals equipped with different systems for ventilation and anaesthetic scavenging. The examined systems included: natural ventilation with supplementary fresh air provided by a pressure ventilation system (up to 6 air changes/h); pressure and exhaust ventilation systems equipped with ventilation units supplying fresh air to and discharging contaminated air outside the working area (more than 10 air changes/h); complete air-conditioning system with laminar air flow (more than 15 air changes/h). The measurements were carried out during surgical procedures (general anaesthesia induced intravenously and maintained with inhaled N(2)O and sevofluran delivered through cuffed endotracheal tubes) with connected or disconnected air scavenging. Air was collected from the breathing zone of operating personnel continuously through the whole time of anaesthesia to Tedlar((R)) bags, and N(2)O concentrations in air samples were analyzed by adsorption gas chromatography/mass spectrometry. RESULTS: N(2)O levels in excess of the occupational exposure limit (OEL) value of 180mg/m(3) were registered in all ORs equipped with ventilation systems alone. The OEL value was exceeded several times in rooms with natural ventilation plus supplementary pressure ventilations and twice or less in those with pressure/exhaust ventilation systems or air conditioning. N(2)O levels below or within the OEL value were observed in rooms where the system of air conditioning or pressure/exhaust ventilation was combined with scavenging systems. Systems combining natural/pressure ventilation with scavenging were inadequate to maintain N(2)O concentration below the OEL value. CONCLUSION: Air conditioning and an efficient pressure/exhaust ventilation (above 12 air exchanges/h) together with efficient active scavenging systems are sufficient to sustain N(2)O exposure in ORs at levels below or within the OEL value of 180mg/m(3).