A multidisciplinary clinical study of patients suffering from illness associated with release of mercury from dental restorations. Medical and odontological aspects.

OBJECTIVE: To describe medical and odontological aspects of patients who believed their illness was caused by mercury in dental fillings. DESIGN: Comparison of self-reported and assessed medical and odontological variables. SETTING: The School of Dentistry, Karolinska Institute. SUBJECTS: Sixty-seven patients, referred for suspected side-effects of mercury in dental fillings, and 64 matched controls. MAIN OUTCOME MEASURES: Incidence of medical and odontological diagnoses, own perception of health, and incidence of self-reported symptoms. RESULTS: Three quarters of the patients were women. The mean age was 49 years. Thirty-seven patients (55%) and 47 controls (73%) (NS) showed no sign of somatic disease. Half of the patients felt ill or very ill at the time of the examination. Patients reported twice as many symptoms as the controls during a 3-month period. Patients reported a higher prevalence of very low resting saliva secretion rate, and a higher number of decayed tooth surfaces and of instances of temporomandibular joint dysfunction. CONCLUSION: Patients' feelings of ill-health were more likely related to psychiatric than somatic diagnoses. This study underlines the importance of making an overall diagnosis, including both mental and somatic disorders, especially in unclear cases and in self-diagnosed illnesses.

A multidisciplinary clinical study of patients suffering from illness associated with mercury release from dental restorations: psychiatric aspects.

The aim of this study was to map the psychological/psychiatric, odontological and medical aspects of patients with symptoms allegedly related to the side-effects of mercury in dental fillings. A total of 67 consecutive patients and 64 controls matched for age, sex and residential area were included in the study. The most striking result was the high prevalence of psychiatric disorders in the patients (89%) compared to the controls (6%), predominantly somatoform disorders. The personality traits differentiating the patients according to the Karolinska Scales of Personality (KSP) were somatic anxiety, muscular tension, psychasthenia and low socialization. More patients than controls showed alexithymic traits. The prevalence of diagnosed somatic diseases was higher, but not sufficiently so to explain the large difference in perceived health. The multiple symptoms and signs of distress displayed by the patients could not be explained either by the odontological data or by the medical examination. Our data indicate that the patients show sociodemographic and clinical patterns similar to those of somatizing patients. The medicalization of the suffering of these patients and the neglect of psychiatric problems prevent the use of appropriate psychotherapeutic approaches.

The dissemination of false data through inadequate citation.

OBJECTIVES: That occupational exposure to mercury causes reproductive failure in dental personnel has been propagated by repeated reference to a single epidemiological study in Poland, published in 1987. The present paper scrutinizes the results of this study, and monitors its subsequent citation in the literature. METHOD: Articles referring to the study were located in the Science Citation Index. From references in these papers and through other references, further articles were found. These papers were reviewed, and their content organized in relation to the way in which the Polish study was cited. RESULT: Most authors referred to the findings in the Polish study without critical evaluation of the data presented. CONCLUSIONS: Citation of irrelevant or misleading scientific data in the literature raises unfounded concerns in nonscientific circles and may lead to unwarranted regulations. It is therefore essential that editors and reviewers of scientific articles also scrutinize the literature quoted.

DMSA administration to patients with alleged mercury poisoning from dental amalgams: a placebo-controlled study.

The present investigation was performed to determine the effect of 14-day oral administration of meso-2.3-dimercaptosuccinic acid (DMSA) on the urinary mercury excretion and the potential reduction of blood and plasma mercury concentrations, and also to relate these effects to possible decrease of symptoms, allegedly associated with amalgam fillings. Twenty subjects, relating their symptoms to mercury from amalgam fillings, received 20 mg/kg DMSA or placebo for 14 days. Their symptoms and mood states were recorded during the study and at a check-up 3 months later. Interpretation was based on intra-individual differences. DMSA-treatment resulted in an average increase in urinary mercury excretion by 65% and a decrease in blood mercury levels of 0.04 microgram/L/day. At the check-up after 3 months, urinary mercury excretion had returned to the pre-treatment level. No treatment effect of DMSA was apparent on subjective symptoms and mood state. One statistically significant treatment effect was noted-a decrease in fatigue-inertia in the DMSA-group-but there was no demonstrable correlation with increased urinary excretion or decreased blood concentration of mercury. Three subjects showed hypersensitive reactions, probably DMSA-specific, at the end of the treatment period. This placebo-controlled study provides no scientific support for diagnostic or therapeutic administration of DMSA for symptoms allegedly associated with chronic mercury exposition from dental amalgam fillings.

Screening tests for systemic effects of dental materials.

Due to the minimal release of compounds from most materials, systemic toxicity effects caused by dental materials have been considered to occur very seldomly or not at all. Screening tests for systemic toxicity are therefore justified only with certain body contact for long periods of time with a dental product. The international standardization on biological evaluation of medical devices has demonstrated a need for improved screening tests and continuous revision of the standards for testing. It is obvious that certain published studies on systemic effects of dental materials and some proposed test methods do not reflect today's demand for toxicokinetic and organ effect studies.

Teratological aspects of dental amalgam.

The teratogenic effect is determined by four factors: (1) the agent, (2) the dose, (3) the stage of embryonic development, and (4) the genetic constitution of the embryo. The first two factors are of particular interest and warrant further comment. It should be emphasized that the mercury released from dental amalgam is mainly metallic mercury vapor. The dose of mercury vapor from dental amalgam fillings in the order of 5 micrograms/day is very low compared with the doses in a teratological study and is not likely to exceed the threshold necessary for a teratogenic effect to occur. The concentration of the teratogen at the target tissue is determined not only by the degree of placental transfer but also by other factors, such as the distribution within the maternal organism, the affinity to the fetal liver and blood, the hematocrit value, and the passage through the ductus venosus. These factors might help to explain toxicological mechanisms and species differences and have to be considered if the results of animal experiments are to be extrapolated to human conditions. Neither epidemiological data nor animal experimental data indicate that the release of metallic mercury vapor from dental amalgam therapy should cause teratogenic effects. A comparison with the incorporation of the fetotoxic methyl mercury might be justified.

Potential teratogenic and carcinogenic effects of dental materials.

Public awareness of potential health hazards from drugs and chemicals is increasing. Doubts about dental materials are also being raised. However, there is a fundamental difference in the magnitude of exposure from potent drugs and from dental materials, which are designed to be as inert and stable as possible; the risk to health could a priori be considered very low. The risk to the patient and to dental personnel should be evaluated separately and based on relevant conditions of exposure and available toxicological data for the specific chemicals released from the dental materials in question. This paper also reviews, briefly, the theories for chemically-induced teratogenic and carcinogenic effects in general, in order to put into perspective suspected adverse reactions to dental materials.

Placental transfer of hexachlorophene (HCP) in the marmoset monkey (Callithrix jacchus).

Autoradiography was used to study the distribution of 2,2'-14C-methylene-bis-(3,4,6-trichlorophenol) (HCP) in pregnant marmoset monkeys in early (day 30-50) and late (around day 120) gestation and in a newborn (11 days old) pup. Radioactivity was present in the conceptus at all stages of gestation, although the foetal concentration was lower than the maternal. In the embryo an accumulation was observed in the neural tube and in the embryonic membranes. In the late foetus and newborn monkey the highest concentration of radioactivity was found in the liver and the intestinal contents. The brain of the adult and newborn animals showed low concentration. A partial blood-brain barrier was present in the late foetus but, in relation to other tissues, the foetal brain concentration was higher than that of the mother.

Influence of a low protein diet on salicylate-induced damage in mice.

The influence of a low protein diet (8%) during pregnancy on the teratogenic potential of sodium salicylate was studied in NMRI mice. Sodium salicylate was given intramuscularly as a single dose of 250 or 500 mg/kg on gestation day 9 or 17. Reduced fetal weight was the only adverse effect of the low protein diet. Following the teratogenic dose of 500 mg/kg, more skeletal malformations were found in fetuses of deficient mothers than of those on a standard diet. An increased incidence of fetal death was demonstrated on gestation day 17 even at the subteratogenic dose of 250 mg/kg.

Increased incidence of congenital malformations in the offspring of diabetic rats and their prevention by maternal insulin therapy.

Intensive care of the pregnant mother with diabetes has dramatically decreased the incidence of diabetic fetopathy. The persistently high rate of fetal and neonatal mortality in diabetic pregnancies is nowadays mainly due to the increased incidence of serious congenital malformations. However, attempts to elucidate the precise teratogenic mechanisms have been sparse, presumably because of a lack of relevant animal models. In the present study we recorded the incidence and types of skeletal malformations in live offspring of normal rats and in rats made diabetic with the B-cytotoxic agent streptozotocin (SZ) at least 2 wk before conception. In some of the diabetic animals insulin treatment was begun 1 wk after the SZ injection and continued throughout pregnancy. In addition, the fetal development was followed by assessing the calcification of the skeleton on gestational days 20 and 22 with the aid of Alazarin Red S staining. Manifest diabetes in the pregnant rat induced a decrease in fetal weight and viability and marked retardation of skeletal maturation. In addition, about 20% of 135 viable fetuses showed skeletal malformations comprising either micrognathia or caudal dysgenesis. These defects were not found in 314 offspring of the control rats. Only two cases of caudal dysgenesis and none of micrognathia were detected among 233 offspring of the insulin-treated rats. The present data underscore the importance of a strict differentiation in the offspring of the diabetic rat between transient development retardations and true malformations. They also demonstrate that correction of the maternal glucose intolerance is crucial for preventing the fetus from developing skeletal malformations. Altogether the data suggest that fetal malformations in the diabetic rat are attributable either to the hyperglycemia as such or to some accompanying metabolic consequence of insulin deficiency.

Agent-determined type of maternal influence on induced cleft palate in mice.

The maternal influence on induced cleft palate frequency, as revealed by reciprocal crosses, was investigated after treatment with triamcinolone or cortisone. Mouse blastocysts from the CBA and A/Jax strains were transferred to pseudopregnant A/Jax and CBA foster mothers and in addition CBA X A/Jax and A/Jax X CBA embryos were raised in pseudopregnant CBA foster mothers. According to the period of maximum sensitivity revealed by a time response study triamcinolone was injected as a single dose (2 mg/kg, i.m.) on day 11 at 8 a.m. when the precocious development of transferred fetuses had been taken into account. A predominant uterine factor slightly modified by the fetal genome was found. This was in contrast to the effect of the 4-day treatment with cortisone (62.5 mg/kg i.m.) where, as also previously has been shown, cytoplasmic factors in the embryos were accountable for the magnitude of the teratogenic response. An increased corticoid elimination from the resistant CBA fetuses might explain the maternal influence on triamcinolone treatment but would not be responsible for the influence on cortisone-induced cleft palate frequency.