Thresholds of adversity for endocrine disrupting substances: a conceptual case study.

For endocrine disrupting chemicals (EDC) the existence of "safe exposure levels", that is exposure levels that do not present an appreciable risk to human health is most controversially discussed, as is the existence of health-based reference values. Concerns have been especially raised that EDCs might not possess a threshold level such that no exposure level to EDCs can be considered safe. To explore whether or not threshold levels can be identified, we performed a screening exercise on 14 pesticidal and biocidal active substances previously identified as EDCs in the European Union. The respective substances are ideal subjects for case studies to review for endocrine activity and disruptive potential following well-defined regulatory assessment based on solid data to effectually establish adversity as consequence of endocrine disruption. Dimethomorph, metiram and propiconazole for which the weight of evidence demonstrating endocrine disruption was the strongest were used as subjects for further study. Epoxiconazole was additionally selected as its effects on the endocrine system are extensive. For all four substances, analysis of the toxicological data clearly indicated thresholds of adversity below which no adverse effects mediated through an endocrine mechanism were observed. Particular emphasis was placed on mechanistic considerations including homeostasis and the concept of adversity. As a proof of concept this study provides evidence that like other substances of toxicological concern EDCs have threshold levels for adversity. While for some EDCs the respective thresholds might indeed be very low this shows that, data allowing, for other EDCs sufficiently protective reference values can be derived.

Subchronic toxicity evaluation of a treated urban sewage sludge.

Disposal of tons of sludge produced daily by sewage treatment plants in large cities is a serious problem. Because recycling and application in agriculture have been proposed, the Brazilian National Environmental Council (CONAMA, 2006) issued a legal norm that regulates the use of the sewage sludge (SS) in crops. Due to the complex chemical nature of such products, characterization by analytical methods for health and environmental risk assessment has severe limitations. To overcome such limitations, it is necessary to (1) assess the toxicological potential of SS and (2) identify possible adverse effects in vivo in order to provide critical information for future environmental regulations. The present study was conducted to determine the potential toxicity of SS obtained from a representative urban treatment plant located in the Sao Paulo State, Brazil. Male and female Wistar rats were fed ad libitum a pelleted diet containing varying amounts of SS. No relevant clinical, hematological, urinary, or gross organ morphological alterations were observed in both genders of rats orally exposed to SS at up to 3.8 g/kg/d for 90 d. Sewage slude produced increased incidence of centrilobular hepatocyte hyperplasia at the high dose and significantly increased aspartate aminotransferease (AST) activities at all doses in both genders. Although the present data indicate some liver involvement, these alterations were considered adaptative and not toxicologically relevant, as the responses were relatively mild, not dose dependent, and no other parameters were markedly affected. The present results may contribute to the establishment of protocols for potential usage in SS agricultural soil application.

In vivo genotoxicity evaluation of a treated urban sewage sludge sample.

Tons of sludge is produced daily in sewage treatment plants of large cities, causing an enormous disposal problem. Because recycling has been proposed to mitigate the situation, the potential adverse health effects of the sludge should be verified before that policy is undertaken. The present study is a part of an assessment of oral toxicity in rats fed with sewer-treated sludge and aimed to contribute to its genotoxicity characterization. After a 2-week acclimatization period, male and female Wistar rats were fed ad libitum for 90 days a pelleted commercial diet containing 0, 5000, 10,000 and 50,000 ppm of a treated sludge sample. The potential mutagenic or genotoxic effect was detected in recent animal cells by the bone marrow micronucleus test and the comet assay, respectively. For the comet assay peripheral blood samples were obtained immediately before the sacrifice from the periorbital plexus. Following sacrifices, polychromatic erythrocytes (PCEs) were analyzed in femoral bone marrow smears and the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) were registered. Results of both assays indicated that exposure to any of the sludge concentrations tested did not increase the frequency of MNPCEs or the levels of DNA damage when compared to non-exposed concurrent control rats.