Mercury is a highly potent cell toxin with effects on human and animal nervous systems. Mercury vapour released from dental amalgam is the predominant source of mercury in the human adult and foetal central nervous system in populations of developed countries. Only in small populations with high consumption of methyl mercury containing fish can the contribution from fish consumption reach or surpass that of amalgam fillings. The most severe health risk is that of interference with foetal and child brain development. This effect of mercury vapour exposure has been demonstrated in animal experiments on monkeys and rats and in nerve cell cultures at nanomolar concentrations. The effect is also supported by epidemiological studies on women occupationally exposed to mercury vapour during pregnancy. However, there is no data permitting an assessment of dose-response relations for this effect in humans. In epidemiological studies on populations with occupational exposure to mercury vapour, subclinical effects on kidneys, the immune system, thyroid function, and CNS function have been observed at an exposure level equal to the upper range of the exposure range seen in amalgam bearers and measured as urine excretion rate of inorganic mercury. The cell toxic effect of mercury is likely to be based on the ability of mercury to modify protein tertiary and quaternary structure. As protein structure is genetically determined, there is ample scope for genetic polymorphism to manifest itself in varying sensitivity and reaction to mercury exposure. It is also likely that mercury exposure from dental amalgam exerts side effects like most potent pharmaceuticals. The clinical support for this assumption is reviewed. An incidence of side effects exceeding 10% is unlikely considering available epidemiological evidence. However, an incidence of 1% or below is highly probable. It is recommended that use of amalgam for dental restorations is abandoned and substituted with available less toxic material and that amalgam restorations in children and women of childbearing age should be avoided due to the potential risk of interference by mercury with brain development.

Timed-pregnant squirrel monkeys were exposed orally to lead during the last 1/2 to 2/3 of gestation such that maternal lead levels ranged from 21 to 70 μg/dl in blood. Offspring of these lead-exposed monkeys were compared to gender-matched, untreated controls (blood-lead levels from 4 to 9 μg/dl), born at about the same time. When the monkeys were 3 to 7 years old they were trained to pull a T-shaped bar against a 1 kg spring through a displacement of 1 cm. This performance was examined during acquisition of different fixed-ratio (1, 5, and 20) and fixed-interval (120″, 300″, and 600″) schedules of reinforcement and during steady state under the fixed-ratio 5 and fixed-interval 600″. Monkeys exposed prenatally to lead showed an increased number of responses failing to meet the requirement of pulling against 1 kg spring through a 1 cm displacement when behavior was maintained by a fixed-ratio schedule, which engenders a vigorous, high-rate pattern of responding. This increased number of incomplete responses first appeared in the acquisition of a fixed-ratio 5 and fixed-ratio 20 schedules of reinforcement, remained after the fixed-ratio 5 schedule was allowed to reach steady state, and did not appear under the fixed-interval schedule. Neither body weight nor response rate were affected by lead, but it was necessary to control for these variables using multiple regression to isolate lead's effect. The appearance of incomplete responses while the monkeys pulled vigorously against a 1 kg spring suggests that lead exposure during gestation produced subtle motor impairments years after exposure has ended. Deficits in the acquisition of behavior (learning) under Concurrent Random Interval schedules of reinforcement have also been reported with these monkeys. Together, these reports reveal prolonged deficits in learning and motor function resulting from in utero exposure to lead at maternal blood lead levels (21–70 μg/dl) that could result from exposure to ambient air in heavily polluted urban environments or in occupational settings meeting current World Health Organization standards.

Exposure to mercury vaporin uteroresults in the accumulation of mercury in the cerebellum, hippocampus, and other regions of the nervous system associated with motor function and learning, but little is known about the functional consequences of prenatal exposure. The offspring of pregnant squirrel monkeys exposed to 0.5 or 1.0 mg/m3of mercury vapor during the last 23 or more of gestation were studied. Median maternal blood levels ranged from 0.025 to 0.18 μg/g and exposures were estimated to range from 20 to 62 μg/day, with cumulative doses of 1304 to 4305 μg. Unexposed monkeys born at about the same time served as controls. The monkeys’ lever pressing was maintained under various Concurrent Random-Interval Random-Interval schedules of reinforcement. Time allocation on each lever was examined during behavioral transitions and in steady state. No difference in sensitivity to reinforcer ratios was identified in steady state, but there was much more variability in the steady-state performance of exposed monkeys, as indicated by the standard deviation of the regression, than in controls. Logistic regression was used to examine the transition to new schedule parameters. Exposed monkeys were found to produce smaller or slower transitions than controls. The magnitude and stability of lever-press durations for controls and exposed monkeys were indistinguishable early in the experiment, but at the end the exposed monkeys had longer lever-press durations and the session-to-session variability was much greater. One monkey's exposure began during the third week of gestation (earlier than any of the others) and the behavior of this monkey was so erratic that some of the analyses could not be accomplished. Long-term effects of prenatal mercury vapor exposure included instability in lever-press durations and steady-state performance under concurrent schedules of reinforcement as well as aberrant transitions. The levels used were close to those reported in occupational settings under conditions of poor hygiene, but were at least 10- to 50-fold greater than those more commonly reported.

Our previous studies have demonstrated that mercury vapour exposure of Brown Norway rats induced an autoimmune response with development of glomerulonephritis and resulted in mercury deposition in the central nervous system, particularly in the neurons. The aim of this study was to investigate the effect on the central nervous system. A loss of Purkinje cells accompanied by Bergmann glial cell proliferation was found at a brain mercury level of 0.71 micrograms/g and became even more pronounced as the exposure dose increased. At a brain mercury level of 5.0 micrograms/g, a heavy gliosis was present in the brain stem, particularly around the pontine nuclei. In comparison with our previous study, the pathological changes in the brain appeared at the same mercury exposure dose as the glomerulonephritis. However, the location of pathological changes at the mercury level of 0.71 micrograms/g was not completely in accordance with the mercury distribution in the brain, which might be due to the sequence of mercury deposition, its amount or the vulnerability of the various cells classes.

Postnatal exposure to lead or methyl mercury results in mental retardation, learning deficits, and other neurobehavioral effects in humans, and adverse consequences of prenatal exposure have been clearly documented with methyl mercury. To examine the developmental neurotoxicity of these metals, especially lead, concurrent schedules of food reinforcement were used to identify learning deficits in squirrel monkeys exposed during gestation to either methyl mercury or lead. Pregnant squirrel monkeys were administered methyl mercury (0.7 to 0.9 ppm in maternal blood) or lead (21 to 79 micrograms/dl in maternal blood) during the last half to two-thirds of gestation. At about 5-6 years of age, offspring were trained to lever press under concurrent schedules of reinforcement in which separate random interval reinforcement schedules operated independently on two levers. Reinforcement densities were varied such that 20 to 90% of the reinforcers were programmed to derive from the left lever (i.e., one lever was "richer" than the other). At steady state, the behavior of the controls was sensitive to reinforcement density and showed little lever bias, but the behavior of monkeys exposed to more than 40 micrograms/dl of lead and to methyl mercury was less sensitive to reinforcement rates and heavily biased. When relative reinforcement density on a lever changed, the unexposed animals' response rates gradually shifted to the newly rich lever. The behavior of monkeys exposed to methyl mercury or more than 40 micrograms/dl of lead changed slowly, not at all, or in the wrong direction. Steady-state behavior of monkeys exposed to less than 40 micrograms/dl resembled controls, but acquisition progressed more slowly and required 2-4 times as many reinforcers to complete. These effects suggest a behavioral mechanism--insensitivity to changing reinforcement contingencies--by which learning deficits and behavioral changes associated with these metals might be related to toxicant exposure. Since maternal blood levels corresponded to those that could be experienced in occupational settings, the present data raise the possibility of fetal hazards associated with maternal lead exposures at levels tolerated in humans in occupational settings.

Subcutaneous injections of mercuric chloride induce an autoimmune glomerulonephritis with both granular and linear IgG deposits along the glomerular capillary wall and proteinuria. This disease is due to a T cell dependent polyclonal B cell activation responsible for production of antibodies against self (glomerular basement membrane, immunoglobulins, DNA, myeloperoxydase) and non self (sheep red blood cells, trinitrophenol (TNP)) components. Increase in serum IgE concentration is the hallmark of this disease. To determine if mercury vapours have pathogenic effects is an important problem of public health. The aim of this study was, first to compare the effects of mercury vapour exposure to those of mercury injections and, second, to compare the effects of high doses to those of low doses of mercury. Two exposure levels were studied corresponding to a mercury absorption of 13.1 mumol/week per kg body wt. and 1.7 mumol/week per kg body wt. during a 5-week period. It will be shown that, whereas the mercury concentration in the kidneys was similar in injected - and vapour exposed - rats, the mercury concentration in blood at the end of the exposure was about twice as high in the injected animals. Blood concentration of mercury was related to dose level but kidney content of mercury was similar in all groups, in spite of a dose difference by a factor of seven between low and high exposure. Mercury vapour and HgCl2 injections both trigger autoimmunity to the same extent and, in both cases the extent of autoimmune manifestations was dose-dependent.

Brown Norwegian rats were exposed to mercury vapor at a concentration of approximately 1 mg/m3 for 5 weeks 24 hr/day 7 days a week and 6 hr/day 3 days a week, respectively. The total mercury absorption was calculated to 264 and 35 μg per week and 100 g body weight. The mean blood mercury concentration was 0.25 ± 0.03 and 0.09 ± 0.01 μg/g, and the total concentration in the brain was 5.03 ± 0.73 and 0.71 ± 0.10 μg/g tissue, respectively. The mercury distribution in the brains was examined using a method based on chemographic principles. Mercury was found primarily in the neocortex, in the basal nuclei, and in the cerebellar Purkinje cells. This distribution pattern corresponded to the pattern of inorganic mercury described after exposure to methyl mercury. Distribution of mercury after administration of different mercury compounds is discussed.

In a retrospective epidemiological study on the birth weight of 266 children of 137 female workers in a nickel-cadmium battery factory, 157 children of workers occupationally exposed to cadmium were compared with 109 born to non-occupationally exposed workers. No effect of cadmium exposure on birth weight was detected, but a statistically significant effect on birth weight of smoking during pregnancy was observed. In a prospective study on the same population of female battery workers, 27 placentas were collected and the cadmium distribution and concentration in tissue subsamples determined. Placental cadmium concentrations were positively correlated with maternal blood cadmium. The cadmium concentration in placentas ranged from < 0.002 to 0.095 microgram/g (wet weight), the mean concentration +/- SD was 0.021 +/- 0.022 microgram/g (wet weight). Morphological and ultrastructural studies of placental tissues did not reveal any effect of cadmium. This study did not provide any evidence in support of the hypothesis that the placenta may be the critical organ in exposure to cadmium.

Annals of the New York Academy of SciencesVolume 534, Issue 1 p. 472-480 Biological Monitoring of Populations Exposed to Volatile Petroleum Products MATHS BERLIN, MATHS BERLIN Monitoring and Assessment Research Centre King's College, London London SW10 0QX, EnglandSearch for more papers by this author MATHS BERLIN, MATHS BERLIN Monitoring and Assessment Research Centre King's College, London London SW10 0QX, EnglandSearch for more papers by this author First published: June 1988 https://doi.org/10.1111/j.1749-6632.1988.tb30136.xCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Berlin, M. 1985. Low level benzene exposure in Sweden: Effect on blood elements and body burden of benzene. Am. J. Ind. Med. 7: 365–373. 2 Berlin, M. & A. Tunek. 1984. Benzene. In Biological Monitoring and Surveillance of Workers Exposed to Chemicals. A. Aitio, V. Riihimaki & H. Vainio, Eds.: 67–81. Hemisphere Publishing Corp. Washington , DC . 3 Berlin, M., J. C. Gage, B. Gullburg, S. Holm, P. Knutsson & A. Tunek. 1980. Breath concentration as an index of the health risk from benzene. Studies on the accumulation and clearance of inhaled benzene. Scand. J. Work Environ. Health. 6: 104–111. 4 Gage, J. C., V. Lagesson & A. Tunek. 1977. A method for the determination of low concentrations of organic vapors in air and exhaled breath. Ann. Occup. Hyg. 20: 127–134. 5 Hunter, C. G. & D. Blair. 1972. Benzene: Pharmacokinetic studies in man. Ann. Occup. Hyg. 15: 193–199. 6 Lauwerys, R. 1983. Benzene. In Human Biological Monitoring of Industrial Chemicals Series. L. Alessio, A. Berlin, R. Roi & M. Boni, Eds. CEC Joint Research Centre. 7 Lauwerys, R. 1983. Toluene. In Human Biological Monitoring of Industrial Chemicals Series. L. Alessio, A. Berlin, R. Roi & M. Boni, Eds. CEC Joint Research Centre. 8 Lindquist, T. 1977. Fördelningskoefficienterna blod/luft och vatten/luft för nagra vanliga lösningsmedel. Arbeta och Hälsa 8: 15. 9 Riihimaki, V. 1984. Xylene. In Biological Monitoring and Surveillance of Workers Exposed to Chemicals. A. Aitio, V. Riihimaki & H. Vainio, Eds.: 67–81. Hemisphere Publishing Corp., Washington , DC . 10 Rusch, G. M., B. J. K. Leong & S. Laskin. 1977. Benzene metabolism. J. Toxicol. Environ. Health 2 (Suppl.): 23–36. 11 Sato, A. & T. Nakajima. 1977. Water/air, blood/air, oil/air, oil/water and oil/blood partition coefficients of some aromatic hydrocarbons. Sangyo Igaku. 19: 132–133. 12 Sherwood, R. J. 1972. Benzene: The interpretation of monitoring results. Ann. Occup. Hyg. 15: 409–421. 13 Sherwood, R. J. 1976. Comparative methods of biological monitoring of benzene exposure. Paper presented to the International Workshop on Toxicology of Benzene. Paris , November 9–11, 1976. 14 Sherwood, R. J. & F. W. G. Carter. 1970. The measurement of occupational exposure to benzene vapour. Ann. Occup. Hyg. 13: 125–146. Citing Literature Volume534, Issue1Living in a Chemical World: Occupational and Environmental Significance of Industrial CarcinogensJune 1988Pages 472-480 ReferencesRelatedInformation

The possible bronchocarcinogenic effects of fumes released during the shielded metal arc welding of stainless steel and the thermal spraying of chromium oxide (Cr2O3) have been studied on the rat. The fume particles were shown to contain tri- and hexavalent chromium in soluble and low soluble forms; they were collected and implanted as pellets in the bronchi of groups of 100 rats by the method of Laskin et al. A negative control group of 100 rats was included, as well as positive controls receiving pellets containing benz(a)pyrene. The experiment was continued for 34 months; no differences of biological significance were noted between the growth rates, survival times, and terminal organ weights of the test and negative control groups. At autopsy, the macroscopic and microscopic appearance of the organs in the three groups, including the local reaction to the implanted pellet, were similar. No precancerous changes were observed at the implantation sites; one rat, who received a pellet containing welding fumes, showed squamous cell carcinoma remote from the implantation site and not associated with the bronchus. It had the appearance of a metastasis. All three benz(a)pyrene control rats developed cancer at the implantation site. The occupational health implications of these findings are discussed.

The value of measurements of zinc protoporphyrin in blood (ZPP) in the surveillance of workers occupationally exposed to lead has been studied. From a group of referents, consisting of 1,088 men and 511 women, it has been established that the normal mean ZPP is in the region of 25 micrograms/100 ml, and only rarely do values exceed 45 micrograms/100 ml. The higher ZPP values are frequently associated with low blood hemoglobin concentrations and appear to be manifestations of an iron-deficiency anemia. Women have higher ZPP values than men; smoking has no influence. Measurements of ZPP and blood lead concentration (PbB) have been made every other month for 2.5 years on a group of around 200 men and 40 women exposed to lead in a storage battery factory. The mean ZPP of the group throughout the period was 70.9 micrograms/100 ml blood, and a linear relation between log ZPP and PbB in the PbB range of 10-80 micrograms/100 ml has been established. ZPP thresholds in the control of excessive occupational lead exposure, and the economic advantage of ZPP measurements over PbB, are discussed.

Measurements for benzene exposure were performed for different work places. In addition, breath benzene concentrations were measured in different occupations in order to establish toxico-kinetics of benzene in man; chromosomal aberrations in lymphocytes of exposed workers were also examined. Smoking appears to result in a large increase in benzene concentration in exhaled breath. The smoke from one cigarette contains 60-80 micrograms of benzene. It was found that exposure levels of 10 ppm are rather uncommon among workers handling gasoline or gasoline equipment. It was concluded that the gasoline load of road tankers cannot be responsible for chromosome changes of the driver, as milk truck drivers showed the same changes. These results did not prove that benzene was the cause of the observed changes. Smoking is the confounding factor, with a potency of at least the same order of magnitude as benzene. In addition, our present knowledge about mechanisms of benzene is not sufficiently developed to permit quantitative conclusions as to the human health risks.