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.

A 30-year-old female dentist was exposed to mercury vapour from a leaking amalgamator for approximately one year. No toxic effect was noted. During and after the exposure urine samples were regularly taken for mercury analysis. The highest value during this period was 60 micrograms Hg/l urine (expressed in micrograms/g creatinine: 42; the normal value for unexposed persons is a few micrograms/g creatinine). The mercury concentration in air was at most 840 micrograms/m3 at the amalgamator (threshold limit for occupational exposure: 50 micrograms/m3). The dentist became pregnant and during pregnancy her average urine mercury concentration was 18 micrograms/g creatinine. Ultrasound examination of the fetus at 20 weeks of gestation showed a mild bilateral hydronephrosis. At 32 weeks of gestation the hydronephrosis had resolved. The dentist gave birth to a normal-weight baby boy, who, at the time of writing, is 2 years of age and appears clinically healthy

Female SJL/N mice were exposed to mercury vapour 5 days/week for 10 weeks, at a mercury concentration of approximately 0.5 mg/m3, 19 h/day; 1 mg/m3, 3 h/day; 0.3 mg/m3, 6 h/day or 1 mg/m3, 1.5 h/day. The total mercury concentrations in the brain were 6.4, 6.3, 1.6 and 0.64 micrograms/g tissue, respectively. The mercury distribution in the brains was examined. Mercury was found in almost the whole brain in the two groups with the highest exposure. In the third group, mercury was primarily found in the neocortical layer V, the white matter, thalamus, and the brain-stem. In the fourth group, the white matter and the brain-stem were the targets for mercury accumulation. Similarities and differences between rats and mice in the distribution pattern are discussed.

Six groups of genetically mercury-susceptible female SJL/N (H-2s) mice were exposed to mercury vapor at a concentration of 0.3-1.0 mg Hg/m3 air for 0.5-19 hr/day 5 days a week for 10 weeks. The absorbed doses were calculated to be between 75 and 2365 μg Hg/week/kg body wt (μg Hg/week/kg). The correlation between the dose and the concentration of Hg in kidney, spleen, and thymus was highly significant (p < 0.0001; Spearman′s rank correlation test). The lowest observed adverse effect level (LOAEL) for serum IgG antinucleolar antibodies (ANoA) was 170 μg Hg/week/kg, corresponding to a renal mercury concentration of 4.0 ± 0.76 μg Hg/g wet wt. The correlation between the absorbed dose and the ANoA titer was highly significant (p < 0.0001; Spearman′s rank correlation test), and all mice were ANoA-positive at a dose of 480 μg Hg/week/kg. High-titer ANoA targeted the nucleolar 34-kDa protein fibrillarin. The LOAEL for B-cell stimulation, measured as an increase in serum IgG2a and IgG1 concentrations, was 360 μg Hg/week/kg, but the increase was fivefold higher and also included IgE at a dose of 690 and 2365 μg Hg/week/kg. The serum Ig concentrations peaked after 2-4 weeks and then slowly declined but, except for IgE, remained significantly increased during the entire exposure time. Glomerular, mesangial IgG immune complex (IC) deposits, accompanied by systemic vessel wall IC deposits, were first detected at a dose of 480 μg Hg/week/kg. The mesangium also showed increased titers of IgM IC deposits and complement factor C3c. The correlation between the absorbed dose, and the individual titer of IgG, IgM, and C3c, was highly significant (p < 0.0001; Spearman′s rank correlation test). In conclusion, mercury vapor efficiently induced an autoimmune syndrome in genetically suceptible mice, and the LOAEL for the adverse effects varied in the order ANoA < B-cell stimulation < IC deposits. Comparing the body burden of mercury in mice at the LOAEL for autoantibodies with the body burden in populations of occupationally exposed humans suggests that the safety margin may be narrow for genetically susceptible individuals.

Pregnant squirrel monkeys were exposed 5 days/week to mercury vapor at a concentration of 0.5 mg Hg/m3 air for 7 hr/day, or at 1 mg Hg/m3 air for 4 or 7 hr/day. The calculated total mercury absorption ranged between 0.8 and 5.4 mg (range of daily absorption 0.04-0.07 mg). The mercury concentration in the cerebral occipital lobe of the offspring ranged between 0.20 and 0.70 μg/g tissue, and in the mothers between 0.8 and 2.58 μg/g tissue. Mapping of the distribution of mercury in the neocortical layers of the maternal brains revealed that the pyramidal cells contained more visualized mercury than the other neurons. In addition, the mapping disclosed that the deeper the pyramidal cells were situated the more mercury they contained. In the offspring brains, no laminar distribution pattern was found. In the hippocampal formation, the pyramidal cells again contained more mercury than the other neurons. By contrast, the stratum granulosa of the dentate gyrus was always devoid of visualized mercury. The claustrum and the amygdaloid complex always contained mercury. In the fiber systems, the offspring brains contained more mercury than the adult brains. Mercury was found in both glial cells and neurons both in the cortical areas and in the fiber systems.

BN, but not LEW, rats treated with subcutaneous injections of mercuric chloride (HgCl2) develop an autoimmune syndrome with infiltration of mononuclear cells into various organs including the oral mucosa. In the present study, we have utilized autometallographic techniques to visualize mercury in the oral mucosa, salivary and lacrimal glands of mercury-sensitive BN and -non-sensitive LEW rats injected with HgCl2. Mercury was deposited intracellularly in dendritic cells that were scattered throughout the lamina propria and submucosal connective tissue of both rat strains. In addition, mercury was detected in dendritic cells appearing within small cell clusters in the juxtaepithelial connective tissue of BN oral mucosa. In salivary and lacrimal glands, mercury was found in dendritic cells scattered throughout the stroma as well as in mononuclear cell foci. Mercury was also found in ductal epithelium. No staining was seen in any of the non-mercury-treated controls. Phenotypic analysis revealed that most mercury-laden cells were ED2+ resident macrophages and that some, but not all, of these cells expressed MHC class II antigens (RT1B).

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.

Experiments comparing the L-dopa histofluorescence method for the visualization of epidermal Langerhans' cells and immunocytochemical labelling with monoclonal anti-T6 antibodies have demonstrated the existence of two functionally different human Langerhans' cells: those that take up L-dopa by a mediated transport and those that lack the capacity to take up L-dopa.

Human epidermal melanocytes can leave their basal position following topical application of sodium lauryl sulphate. They thereby undergo changes which strongly indicate that the dense plates along their cytomembrane constitute a mechanism for attachment to the basal lamina. These detached melanocytes move rapidly to, or are transported to, more superficial levels of the living epidermis. They are probably not desquamated, but disintegrate within the stratum spinosum. It was remarkable that one melanocyte was found that broke the basal lamina, showing that melanocytes are capable of migrating, under certain conditions. A special fixation method which exposes the cytomembranes and allows the demarcation of cells and their finest cytomembrane protrusions was used to demonstrate that keratinocytes often bulge into the innermost spinous layer and become attached to the basal lamina only via more or less thin cytoplasmic protrusions. This is in contrast to the routine textbook description of a basal layer that consists of a strict single row of cuboid or columnar keratinocytes.

Topical anesthesia with ethyl chloride spraying generates some remarkable reactive events in the human Langerhans' cell (LC) system. Many LC retract their dendrites and a considerable number move to the innermost layers of the epidermis within 15 minutes. This rapid motility supports the view that the interstices between cells in living epidermis are large. The LC cytomembrane is very susceptible to cold shock which causes the cytomembrane to superimpose upon itself forming abnormally shaped Birbeck granules. This process may consume too much of the cytomembrane to be compatible with cell survival.

Electron microscopic examination of over 100 dendritic cells in human keratinized gingiva has shown that the indeterminate cells are not a separate cell type. This approach disclosed the sources of error which have led to the commonly held, but erroneous, view that there exist numerous indeterminate cells in this epithelium. Two interesting differences were found between gingival and epidermal Langerhans cells. The number of Birbeck granules in the former cells can be extremely low while they occur frequently in the epidermal cells, and granules in their formative stage are commonplace in the gingival cells but rare in the epidermal cells.

The effects on the basal and spinous layers of human keratinized oral epithelium of 2 glutaraldehyde-based fixatives with buffers hypoosmolar and isoosmolar to blood, respectively, have been investigated. The first-mentioned solution produced an electron microscopic image corresponding to the classical view, that is an epithelium consisting of closely-packed cells having short and stubby membrane projections and separated by an extremely narrow intercellular space. In the Langerhans cells, the specific granules appeared racket-shaped and had a unilaminar limiting membrane with a periodic structure along its internal face. There are strong reasons to believe that these morphological characteristics are swelling artifacts. The last-mentioned fixative produced keratinocytes provided with numerous microvilli and membrane ruffles and disk-shaped Langerhans cell granules surrounded by a trilaminar membrane. Concomitantly, the intercellular space appears very wide and there is evidence for the view that this is a more realistic picture of the in vivo situation and not a gross distortion caused by shrinking during the tissue processing. Broad interstices can explain certain basic events as rapid cell motility within the epithelium and offer efficient pathways for rapid transport of substances.