Occup Environ Med. 1994 Jan;51(1):28-34.
The effect of occupational exposure to mercury vapour on the fertility of female dental assistants.
Rowland AS, Baird DD, Weinberg CR, Shore DL, Shy CM, Wilcox AJ.
Source: Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Exposure to mercury vapour or inorganic mercury compounds can impair fertility in laboratory animals. To study the effects of mercury vapour on fertility in women, eligibility questionnaires were sent to 7000 registered dental assistants in California. The final eligible sample of 418 women, who had become pregnant during the previous four years, were interviewed by telephone. Detailed information was collected on mercury handling practices and the number of menstrual cycles without contraception it had taken them to become pregnant. Dental assistants not working with amalgam served as unexposed controls. Women with high occupational exposure to mercury were less fertile than unexposed controls. The fecundability (probability of conception each menstrual cycle) of women who prepared 30 or more amalgams per week and who had five or more poor mercury hygiene factors was only 63% of that for unexposed women (95% CI 42%-96%) after controlling for covariates. Women with low exposure were more fertile, however, than unexposed controls. Possible explanations for the U shaped dose response and limitations of the exposure measure are discussed. Further investigation is needed that uses biological measures of mercury exposure.
In laboratory mice, rats, and hamsters, chronic exposure to inorganic mercury compounds disrupts the oestrous cycle,"S impedes follicular developrnent,2 and impairs embryo implantation.5 Only one study has examined the of mercury vapour on fertility, reporting lengthening of the oestrous cycle and reductions in the number of implantations in exposed rats, but no diflerenccs in the number of mated females that became pregnant.6
Little is known about the reproductive toxicity of mercury vapour in humans. Six studies, mostly conducted in Eastern Europe, have reported abnormalities of the menstrual cycle including painful menstruation and changes in bleeding patterns and menstrual cycle duration among workers exposed to mercury'"; "two of these studies involved dental workers.m
Although mercury is poorly absorbed through the skin and gastrointestinal tract, mercury vapour is efficiently absorbed through the lung.13 The dissolved vapour remains in the blood long enough to cross the blood brain barrier where it is oxidised and eliminated only very slowly." Necropsy studies of occupationally exposed subjects have found high concentrations of mercury in the pituitary, thyroid, and brain1516 and there is evidence that mercury persists in these tissues for many years." Whether the mercury that accumulates is biologically-active'and therefore to interfere with endocrine or reproductive function is not known. Three small studies";-2° have looked at pituitary and thyroid function in subjects with chronic exposure to mercury vapour. The results were ambiguous; pituitary and thyroid function seemed clinically normal but there were differences in prolactin or sex hormone binding globulin concentrations that might suggest an underlying effect.
The evidence that mercury accumulates in the brain, pituitary, and thyroid, that it disrupts ovulation in animals, and that women exposed to mercury experience abnormal menstrual cycles suggests that mercury vapour may impair fertility in humans'
To date there have been no epidemiological studies of the effect of mercury vapour on human female fertility. The purpose of this study was to invesn'gate such effects among female dental assistants. Mercury is a principal component of the silver amalgam used to fill teeth. In most dental offices it is the job of the dental assistant to prepare the amalgam. Consequently most dental assistants are chronically exposed to low concentrations of mercury vapour unless they Work in specialties like orthodontics or oral surgery and do not handle amalgam. As a group, dental assistants have urinary mercury concentrations higher than the general population or other dental personnel,21 and cases of mercury poisoning have occasionally been reported.22 Most dental assistants, however, have urinary mercury concentrations well below 50 Izreatinine,2l the recommended exposure limit proposed by the World Health Organisation."
In this study, subfextility was assessed retrospectively by collecrjng information on time to pregnancy," defined as the number of menstrual cycles women took to become pregnant, adjusted for their frequency of unprotected sexual intercourse. This retrospective method of studying fertility" has been used to investigate the effects of such factors as oral contraceptive use" and cigarette smoking2627 and may be a sensitive screening tool for evaluating occupational exposures as well.
Women with-occupational exposure to mercury vapour (30 or more amalgams per week and four or more poor mercury hygiene factors) showed evidence of reduced fertility in this dataset. This is consistent with animal experiments and with reports of menstrual cycle problems among women with occupationalexposure to mercury.
Our study relied on detailed descriptions of the work environment and mercury handling practices to infer amounts of exposure to mercury vapour based on previous research that has correlated urinary mercury concentrarions or air monitoring results with mercury hygiene factors in the dental (table 1). Among groups of women preparing the same number of amalgams we found difietences in fecundability based on the dental assistant's reported number of poor mercury hygiene factors. This suggests that detailed occupational hygiene scales may be useful in other questionnaire studies of occupational disease because occupational groups with roughly the same potential for exposure often contain subjects whose actual exposures are quite difierent depending on their particular work environment and their work practices within that environment.
Although most dental offices have mercury vapour levels well below the OSHA permlssible exposure limit of most studies have identified a group of offices with exposures above this level22 5' 5' (about 10% to 20% of the surveyed). Twenty per cent of the women in our final sample reported preparing more than 30 amalgams per week with four or more poor hygiene factors. Even though we do not have biological measures of exposure, it seems likely- that many of these women may have worked in with exposures approaching or exceeding the permissible exposure limit.
An important limitation of using data on hygiene factors to estimate exposure is that it often will be correlated with other occupational or personal lifestyle exposures. Although we evaluated other potential occupational exposures of concern such as use of nitrous oxide, x rays, and sterilants as well as many lifestyle factors such as smoking, alcohol, and recreational drug use, our finding of reduced fertility among women in our high mercury group could reflect other exposures found among women working in offices with poor hygiene and many amalgams_
Our exposure measure was based on exposure around the time each woman began her attempt to become pregnant, not cumulative lifetime occupational exposure. To assess the effects of past exposure, we used data from the screening questionnaire to construct a cumulative index of lifetime number of amalgams placed before the reference date. There was no relation between cumulative lifetime number of amalgams placed and fertility although this number was only a crude approximation of lifetime mercury exposure.
Unexposed women in our study had lower fertility than low exposed women (but better fertility than women in the two highest exposure groups.) This pattern was consistently present within the univariate (tables 5 and 6) and the multivariate data (tables 3 and 4) but is not one that we can readily explain. One hypothesis we considered was that our "unexposed" group may have had other unmeasured occupational exposures that reduced their fertility. The unexposed group included both women who worked in orthodontic offices and a group of women from various other subspecialties who did not work with amalgam. Both groups showed similar lower fertility than the low exposed group, indicating that it was not due to some exposure exclusive to orthodontic the largest subgroup within the unexposed women. More detailed data on other exposures incurred by dental assistants who do not work with amalgam would be needed to explore this further. We also explored the possibility that the low exposed group were primarily administrative personnel who were different in other respects. Examining such variables as family income, gravidity, and seniority in the job, however, did not support this hypothesis, In fact, the study sample is restricted to one occupational group and demographically is quite homogeneous.
Another possible explanation for the U shaped dose response is that it may have been influenced by different participation rates between the unexposed and the low exposed. Unexposed women may have been less likely to participate. Among those who did, a disproportionate number may have been disposed to cooperate, in part, because they were having fertility problems. Unfortunately, we were unable to explore this possibility further because the dental assistant registry included no data on the subspecialty of the offices in which women worked.
Finally, a biological explanation for higher fertility among the low exposed women is possible. Predosing animals with low amounts of cadmium or mercury reduces the toxiciry of subsequent, higher exposures to these The underlying mechanism for these results is believed to involve induction of merallothioncin, an intracellular pro
tein that binds and dctoxifies metals.""" Experimental evidence also suggests that mctallothionein may offer some protection against low level exposures to x rays, free radicals, and alkylating agents.'55 Further research is needed before the plausibility of this hypothesis can be adequately addressed.
We found reduced fertility among the two groups of women in our study with the highest estimated exposure to mercury vapour, and a suggestion of dose response trends in the fecundability ratios among the two highest categories of number of amalgams and the two highest categories of poor hygiene factors. This provides iimited evidence that metcury vapour may impair female fertility and justification for more intensive epidemiological study of the reproductive toxicity of mercury. In the interim, dental personnel would be wise to err on the side of caution and implement the already well established guidelines for good meicury hygiene."