Viadent usage and oral leukoplakia: a spurious association.

Oral rinse and toothpaste products (Viadent) containing Sanguinaria extract have been shown through extensive clinical trials to be effective against plaque build-up and gingivitis. To establish safety, a comprehensive research program was conducted, including a series of clinical studies and a number of animal studies to evaluate acute, subchronic, and chronic toxicity, and the potential for irritation of mucosal tissues. In 1990 and 1993, an Expert Panel reported on reviews of these data and concluded that Viadent products are safe for their intended use. Despite the large database of information to support the safety of Viadent products, Damm et al. (1999) recently raised the possibility that their usage may be causally associated with development of oral leukoplakia. However, a critique of this recent report shows that it does not fulfil criteria for establishing causation. In particular, the study does not show that exposure to Viadent preceded the onset of leukoplakia, it does not demonstrate dose-response or biological plausibility, and it suffers from selection and information bias and from potential confounding. Furthermore, upon critical evaluation, the Damm et al. (1999) report on a case-series is inconsistent with the weight of available clinical evidence showing that Sanguinaria extract-containing oral health care products cause no cytotoxic or significant irritant effects in the oral mucosa in human studies of up to 6 months duration. The animal data similarly do not support a causal association between Viadent usage and oral leukoplakia in humans. These data demonstrate that Sanguinaria extract and whole Viadent formulations are without significant irritation potential and have no effects on the oral mucosa, even in studies with life-long dietary exposure to Sanguinaria extract. The mutagenicity and genotoxicity data do not indicate that Sanguinaria extract or its components are genotoxic in vivo. The results of 2 GLP-compliant rat oncogenicity studies provide no evidence of any carcinogenic effect of Sanguinaria extract. In conclusion, the available clinical and animal data provide no support for and in fact argue strongly against the hypothesis that the use of Viadent toothpaste and/or oral rinse products may be causally associated with the development of leukoplakia in humans.

Familial aggregation of multiple myeloma and central nervous system diseases.

Degenerative central nervous system diseases such as Alzheimer's disease and lymphoreticular malignancies such as multiple myeloma occur with increased frequency with advancing age. Relatives of early-onset Alzheimer's disease patients may have an increased risk of lymphoreticular malignancies. This led us to evaluate the family history of central nervous system diseases in a case-control study of multiple myeloma. Thirteen of 439 multiple myeloma cases had one or more first-degree relatives with degenerative or demyelinating central nervous system disease. In comparison, there were nine "positive" family histories in 1,317 matched hospital controls (relative risk = 4.4, 95% confidence interval = 1.9-10.3). Relative risks for the component categories of Parkinson's disease, multiple sclerosis, and miscellaneous degenerative central nervous system diseases were 3.0, 4.0 and 11.9, respectively. Our findings suggest that the degenerative and demyelinating central nervous system diseases and the lymphoreticular malignancies may comprise an etiologically related group of "protean diseases." These diseases may have a shared genetic susceptibility, possibly an immunologic abnormality. The varied disease manifestation in family members suggests a second necessary etiologic step of a variable and possibly environmental nature.

Parents' cigarette smoking and childhood cancer.

In our recent study of childhood rhabdomyosarcoma (RMS) we found an increase in the risk of RMS among children whose fathers smoked cigarettes. However, there was no association between RMS and mothers' smoking. We hypothesize that differential germ cell damage from cigarette smoking underlies our observations and that this risk of germ cell damage from cigarette smoking and from other environmental exposures is greater for men than for women. The increased susceptibility for male germ cells may be due to the number and timing of meiotic and mitotic cell divisions. In males, germ cells undergo large numbers of meiotic and mitotic divisions throughout the reproductive years. In contrast, in females, generally only one oocyte matures and completes meiosis each month of the reproductive years. Thus, there are very large male-female differences in the number of rapidly dividing germ cells during the reproductive years, and it is rapidly proliferating cells which are most susceptible to genetic damage. We conclude that fathers' environmental exposures before conception of their children may play a role in the etiology of childhood cancer.

Environmental factors in the etiology of rhabdomyosarcoma in childhood.

In a case-control study of childhood rhabdomyosarcoma (RMS), families of 33 cases and 99 controls were interviewed. A relative risk (RR) of 3.9 was found associated with fathers' (but not mothers') cigarette smoking (P = 0.003). Cases had had fewer immunizations than controls, particularly smallpox vaccination (RR = 0.2; P = 0.001), and conversely had more preventable infections. An RR of 3.2 (P = 0.03) was found associated with exposure to chemicals and and RR of 3.7 (P = 0.004) was found associated with diets that included organ meats. Mothers of cases were more likely to be over age 30 years at subject's birth, to have used antibiotics preceding or during pregnancy, and to have had an overdue and/or assisted delivery. Other findings suggest that low socioeconomic status is associated with an increased risk of RMS. These aggregate findings imply that environmental factors may play an important role in the etiology of childhood RMS.