Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food.

The European Commission asked EFSA to update its 2011 risk assessment on polybrominated diphenyl ethers (PBDEs) in food, focusing on 10 congeners: BDE-28, -47, -49, -99, -100, -138, -153, -154, -183 and ­209. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour and reproductive/developmental effects are the critical effects in rodent studies. For four congeners (BDE-47, -99, -153, -209) the Panel derived Reference Points, i.e. benchmark doses and corresponding lower 95% confidence limits (BMDLs), for endpoint-specific benchmark responses. Since repeated exposure to PBDEs results in accumulation of these chemicals in the body, the Panel estimated the body burden at the BMDL in rodents, and the chronic intake that would lead to the same body burden in humans. For the remaining six congeners no studies were available to identify Reference Points. The Panel concluded that there is scientific basis for inclusion of all 10 congeners in a common assessment group and performed a combined risk assessment. The Panel concluded that the combined margin of exposure (MOET) approach was the most appropriate risk metric and applied a tiered approach to the risk characterisation. Over 84,000 analytical results for the 10 congeners in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary Lower Bound exposure to PBDEs were meat and meat products and fish and seafood. Taking into account the uncertainties affecting the assessment, the Panel concluded that it is likely that current dietary exposure to PBDEs in the European population raises a health concern.

Assessment of 9-OH- and 7,8-diol-benzo[a]pyrene in Blood as Potent Markers of Cognitive Impairment Related to benzo[a]pyrene Exposure: An Animal Model Study.

The potent neurotoxicity of benzo[a]pyrene (B[a]P) has been suggested to be a susceptibility factor accelerating the onset of brain tumours and the emergence of neurobehavioural disturbances. B[a]P has been shown to be neurotoxic, acting directly on both the central and peripheral nervous systems, as well as indirectly via peripheral organs like liver and gut. By using a realistic B[a]P exposure scenario (0.02-200 mg/kg/day, 10 days) in mice, we elucidated brain-specific B[a]P metabolism and at identified hydroxylated B[a]P metabolites in serum which could be used as markers of cognitive impairment. Repeated oral administration of B[a]P led to, at the doses of 20 and 200 mg/kg/day, significant overexpression of Cyp1a1/Cyp1b1 in 2 out of the 3 brain regions considered, thereby suggesting the ability of the brain to metabolize B[a]P itself. At the same doses, mice exhibited a reduction in anxiety in both the elevated plus maze and the hole board apparatus. Concomitantly, B[a]P triggered dose-dependent changes in Nmda subunit expression (Nr1 and Nr2a/Nr2b) in areas involved in cognition. We detected 9-OH-B[a]P and 7,8-diol-B[a]P in serum at the level for which cognitive impairment was observed. We suggest that these metabolites may, in the future be exploited as potent biomarkers of B[a]P-induced cognitive impairments.

Regulatory identification of BPA as an endocrine disruptor: Context and methodology.

BPA is one of the most investigated substances for its endocrine disruptor (ED) properties and it is at the same time in the center of many ED-related controversies. The analysis on how BPA fits to the regulatory identification as an ED is a challenge in terms of methodology. It is also a great opportunity to test the regulatory framework with a uniquely data-rich substance and learn valuable lessons for future cases. From this extensive database, it was considered important to engage in a detailed analysis so as to provide specific and strong evidences of ED while reflecting accurately the complexity of the response as well the multiplicity of adverse effects. An appropriate delineation of the scope of the analysis was therefore critical. Four effects namely, alterations of estrous cyclicity, mammary gland development, brain development and memory function, and metabolism, were considered to provide solid evidence of ED-mediated effects of BPA.

Short-term effects of a perinatal exposure to the HBCDD α-isomer in rats: Assessment of early motor and sensory development, spontaneous locomotor activity and anxiety in pups.

The present study investigated the developmental neurotoxicity of an early exposure to α-HBCDD through the ingestion of contaminated hen's egg in pregnant and lactating Wistar female rats. Hens were given α-HBCDD-contaminated feed (40 ng/g fresh matter) for 5 and 10 days, which produced eggs with HBCDD content of 33 and 102 ng/glipid weight, respectively. Female rats were administered daily p.o. with an appropriate volume of the whole egg from the day of fertilization (GD0) to the weaning day for pups (PND21). Fetuses and pups were thus exposed continuously to α-HBCDD via the dam over a whole 42-day period that included both gestation and lactation. The administered egg volume was calculated on the basis of daily egg consumption in humans (0.7 egg/person/day) and duration of gestation and lactation in both species, which led animals to be exposed to α-HBCDD at levels of 22 and 66 ng/kg/day, respectively. Neurobehavioral development of pups was investigated from PND3 to PND25 using various tasks including the righting reflex (PND4), the grasping reflex (PND5), the negative geotaxis (PND9), the forelimb grip strength test (PND10) and the locomotor coordination test (PND20). Pup ultrasonic vocalizations were also recorded daily from PND4 to PND14. After weaning, behaviors related to spontaneous locomotor activity and anxiety were examined in the open-field (PND25) and in an elevated-plus maze (PND26), respectively. The results showed a significant decrease in body weight of pups exposed to the lower HBCDD level from PND3 to PND28, whereas the weight of rat pups given 66 ng/kg/day of HBCDD was not different from controls. During the first 3 weeks of life, impairments in motor maturation of pups were observed in a dose-dependent manner depending on the test, whereas no significant differences were reported between male and female pups. At PND26, the anxiety level of female rats exposed to the lowest dose of HBCDD (22 ng/kg/day) was significantly reduced whereas it remained unchanged in males. No significant variations were measured in rats exposed to the higher level of HBCDD (66 ng/kg/day). These results suggest the potent developmental neurotoxicity of an early chronic exposure to the HBCDD α-isomer through the ingestion of hen's eggs contaminated with this pollutant and question the long-lasting consequences of this exposure on behavior abilities and brain functioning in adulthood.

Short-term effects of a perinatal exposure to a 16 polycyclic aromatic hydrocarbon mixture in rats: assessment of early motor and sensorial development and cerebral cytochrome oxidase activity in pups.

Humans are exposed to polycyclic aromatic hydrocarbons (PAHs), a family of ubiquitous neurotoxic pollutants, mainly through ingestion of contaminated food. Developing organisms can be exposed also to PAHs due to the ability of these compounds to pass through the placental barrier as well as through the breast milk. Previous animal studies have reported that the exposure of rats to a 16 PAH mixture at environmental doses strictly limited to gestation did not induce any long-lasting consequences, whereas gestational and lactational PAH exposure induced long-term behavioral and cerebral metabolic effects. In the present study, short-term effects of exposures to the same PAH mixture during gestation, or during gestation and lactation, were assessed by evaluating motor and sensory development of rat pups, and by measuring cerebral cytochrome oxidase activity (a marker of energetic metabolism) in different brain areas. Brain levels of PAHs and some monohydroxylated metabolites were also evaluated in pups at birth and at 21 days of postnatal life. No significant short-term modifications of behavioral development and of cerebral metabolism were observed following an early PAH exposure whatever the dose and the period of exposure. Surprisingly, the same brain levels of concentration of PAHs and metabolites were observed in control and exposed pups in both studies. These analytical results raise the difficulty in overcoming environmental contamination of control animals and the choice of such controls in experimental studies which focus on neurotoxicity of exposure to low levels of pollutants.