A Multi-Phase Anglo-Saxon Site in Ewelme

New evidence is presented for a middle Anglo-Saxon ‘productive’ site on hilly ground north-west of Ewelme in south Oxfordshire. Coins and other finds from metal-detecting activity suggest the existence of an eighth- to ninth-century meeting or trading point located close to the Icknield Way. Th is place takes on an added significance because of its proximity to an early Anglo-Saxon cemetery and probably a late Anglo-Saxon meeting place. Th e authors provide an initial assessment of the site, its likely chronological development and its relationship with wider Anglo-Saxon activity in the upper Thames region and beyond. Some suggestions are made about the implications of the existence of such a long-lasting or recurring centre of activity for early medieval inhabitants’ perceptions of landscape

The ‘Lost’ Church of Bix Gibwyn: The Human Bone

Recent research for the Victoria County History (VCH) highlighted the presence of a ‘lost’ medieval church in Bix, a Chilterns parish north-west of Henley-on-Thames. The building, formerly the parish church of Bix Gibwyn, was abandoned in the late sixteenth or seventeenth century and has left no standing remains. Archaeological investigation by the South Oxfordshire Archaeological Group (SOAG) and Reading University has confirmed its location in a close called ‘Old Chapel’ in Bix Bottom, in the north of the parish. The rediscovery of the site – which contains the foundations of a hitherto unknown Romano-British stone building – sheds new light on long-term changes in local communications, settlement, and economic conditions. In the Middle Ages Bix Gibwyn church was a focus of religious and social life for a small rural community in the south Oxfordshire Chilterns. After the Reformation it was neglected, demolished, and finally all but forgotten. Its location has been a matter of speculation for over a hundred years,1 but in 2007–10 its churchyard was identified through a combination of historical research and archaeological fieldwork. Confirmation of the church’s location in the remote Bix Bottom valley provides important evidence about the medieval settlement pattern in Bix, which was very different from the modern one, and offers an opportunity to reassess the development of settlement in the southern Chilterns more generally. The archaeological findings also supply new evidence about Roman activity in the area

Alterations in Central Nervous System Serotonergic and Dopaminergic Synaptic Activity in Adulthood after Prenatal or Neonatal Chlorpyrifos Exposure

Exposure to chlorpyrifos (CPF) alters neuronal development of serotonin (5HT) and dopamine systems, and we recently found long-term alterations in behaviors related to 5HT function. To characterize the synaptic mechanisms underlying these effects, we exposed developing rats to CPF regimens below the threshold for systemic toxicity, in three treatment windows: gestational days (GD) 17–20, postnatal days (PN) 1–4, or PN11–14. In early adulthood (PN60), we assessed basal neurotransmitter content and synaptic activity (turnover) in brain regions containing the major 5HT and dopamine projections. CPF exposure on GD17–20 or PN1–4 evoked long-term increases in 5HT turnover across multiple regions; the effects were not secondary to changes in neurotransmitter content, which was unaffected or even decreased. When the treatment window was shifted to PN11–14, there were no long-term effects. Dopamine turnover also showed significant increases after CPF exposure on GD17–20, but only when the dose was raised above the threshold for overt toxicity; however, hippocampal dopamine content was profoundly subnormal after exposures below or above the acute, toxic threshold, suggesting outright neurotoxicity. These results indicate that, in a critical developmental period, apparently nontoxic exposures to CPF produce lasting activation of 5HT systems in association with 5HT-associated behavioral anomalies

Ten Years of Mixing Cocktails: A Review of Combination Effects of Endocrine-Disrupting Chemicals

In the last 10 years, good evidence has become available to show that the combined effects of endocrine disruptors (EDs) belonging to the same category (e.g., estrogenic, antiandrogenic, or thyroid-disrupting agents) can be predicted by using dose addition. This is true for a variety of end points representing a wide range of organizational levels and biological complexity. Combinations of EDs are able to produce significant effect, even when each chemical is present at low doses that individually do not induce observable effects. However, comparatively little is known about mixtures composed of chemicals from different classes of EDs. Nevertheless, I argue that the accumulated evidence seriously undermines continuation with the customary chemical-by-chemical approach to risk assessment for EDs. Instead, we should seriously consider group-wise regulation of classes of EDs. Great care should be taken to define such classes by using suitable similarity criteria. Criteria should focus on common effects, rather than common mechanisms. In this review I also highlight research needs and identify the lack of information about exposure scenarios as a knowledge gap that seriously hampers progress with ED risk assessment. Future research should focus on investigating the effects of combinations of EDs from different categories, with considerable emphasis on elucidating mechanisms. This strategy may lead to better-defined criteria for grouping EDs for regulatory purposes. Also, steps should be taken to develop dedicated mixtures exposure assessment for EDs

Developmental Exposure of Rats to Chlorpyrifos Leads to Behavioral Alterations in Adulthood, Involving Serotonergic Mechanisms and Resembling Animal Models of Depression

Developmental exposure to chlorpyrifos (CPF) causes persistent changes in serotonergic (5HT) systems. We administered 1 mg/kg/day CPF to rats on postnatal days 1–4, a regimen below the threshold for systemic toxicity. When tested in adulthood, CPF-exposed animals showed abnormalities in behavioral tests that involve 5HT mechanisms. In the elevated plus maze, males treated with CPF spent more time in the open arms, an effect seen with 5HT deficiencies in animal models of depression. Similarly, in an anhedonia test, the CPF-exposed group showed a decreased preference for chocolate milk versus water. Developmental CPF exposure also has lasting effects on cognitive function. We replicated our earlier finding that developmental CPF exposure ablates the normal sex differences in 16-arm radial maze learning and memory: during acquisition training, control male rats typically perform more accurately than do control females, but CPF treatment eliminated this normal sex difference. Females exposed to CPF showed a reduction in working and reference memory errors down to the rate of control males. Conversely, CPF-exposed males exhibited an increase in working and reference memory errors. After radial-arm acquisition training, we assessed the role of 5HT by challenging the animals with the 5HT(2) receptor antagonist ketanserin. Ketanserin did not affect performance in controls but elicited dose-dependent increases in working and reference memory errors in the CPF group, indicating an abnormal dependence on 5HT systems. Our results indicate that neonatal CPF exposures, classically thought to be subtoxic, produce lasting changes in 5HT-related behaviors that resemble animal models of depression

Exposure to Organophosphates Reduces the Expression of Neurotrophic Factors in Neonatal Rat Brain Regions: Similarities and Differences in the Effects of Chlorpyrifos and Diazinon on the Fibroblast Growth Factor Superfamily

BACKGROUND: The fibroblast growth factor (FGF) superfamily of neurotrophic factors plays critical roles in neural cell development, brain assembly, and recovery from neuronal injury. OBJECTIVES: We administered two organophosphate pesticides, chlorpyrifos and diazinon, to neonatal rats on postnatal days 1-4, using doses below the threshold for systemic toxicity or growth impairment, and spanning the threshold for barely detectable cholinesterase inhibition: 1 mg/kg/day chlorpyrifos and 1 or 2 mg/kg/day diazinon. METHODS: Using microarrays, we then examined the regional expression of mRNAs encoding the FGFs and their receptors (FGFRs) in the forebrain and brain stem. RESULTS: Chlorpyrifios and diazinon both markedly suppressed fgf20 expression in the forebrain and fgf2 in the brain stem, while elevating brain stem fgfr4 and evoking a small deficit in brain stem fgfr22. However, they differed in that the effects on fgf2 and f4 were significantly larger for diazinon, and the two agents also showed dissimilar, smaller effects on fgf11, fgf14, and fgfr1. CONCLUSIONS: The fact that there are similarities but also notable disparities in the responses to chlorpyrifos and diazinon, and that robust effects were seen even at doses that do not inhibit cholinesterase, supports the idea that organophosphates differ in their propensity to elicit developmental neurotoyicity, unrelated to their anticholinesterase activity. Effects on neurotrophic factors provide a mechanistic link between organophosphate injury to developing neurons and the eventual, adverse neurodevelopmental outcome

Low-Level Exposure to Multiple Chemicals: Reason for Human Health Concerns?

BACKGROUND: A key question in the risk assessment of exposures to multiple chemicals is whether mixture effects may occur when chemicals are combined at low doses which individually do not induce observable effects. However, a systematic evaluation of experimental studies addressing this issue is missing. OBJECTIVES: With this contribution, we wish to bridge this gap by providing a systematic assessment of published studies against well-defined quality criteria. RESULTS: On reviewing the low-dose mixture literature, we found good evidence demonstrating significant mixture effects with combinations of chemicals well below their individual no observable adverse effect levels (NOAELs), both with mixtures composed of similarly and dissimilarly acting agents. CONCLUSIONS: The widely held view that mixtures of dissimilarly acting chemicals are "safe" at levels below NOAELs is not supported by empirical evidence. We show that this view is also based on the erroneous assumption that NOAELs can be equated with zero-effect levels. Thus, on the basis of published evidence, it is difficult to rule out the possibility of mixture effects from lowdose multiple exposures