A perspective on In vitro developmental neurotoxicity test assay results: An expert panel review.

For decades, there has been increasing concern about the potential developmental neurotoxicity (DNT) associated with chemicals. Regulatory agencies have historically utilized standardized in vivo testing to evaluate DNT. Owing to considerations including higher-throughput screening for DNT, reduction in animal use, and potential cost efficiencies, the development of alternative new approach methods (NAMs) occurred; specifically, the advent of the DNT in vitro test battery (DNT IVB). SciPinion convened an expert panel to address specific questions related to the interpretation of in vitro DNT test data. The consensus of the expert panel was that the DNT IVB might be used during initial screening, but it is not presently a complete or surrogate approach to determine whether a chemical is a DNT in humans. By itself, the DNT IVB does not have the ability to capture nuances and complexity of the developing nervous system and associated outcomes including behavioral ontogeny, motor activity, sensory function, and learning/memory. Presently, such developmental landmarks cannot be adequately assessed in the DNT IVB or by other NAMs. The expert panel (all who serve as co-authors of this review) recommended that additional data generation and validation is required before the DNT IVB can be considered for application within global regulatory frameworks for decision-making.

Risk of nonsteroidal anti-inflammatory drug-associated renal dysfunction among neonates diagnosed with patent ductus arteriosus and treated with gentamicin.

OBJECTIVE: To evaluate the risk of nonsteroidal anti-inflammatory drug (NSAID) therapy-associated acute kidney injury (AKI) among neonates diagnosed with patent ductus arteriosus (PDA) who are treated with gentamicin. STUDY DESIGN: Multicenter retrospective observational study of patients ⩽44 postmenstrual weeks of age diagnosed with PDA who received gentamicin during hospitalization between January 2006 and December 2014. Patients with and without NSAID exposure were matched on covariates associated with AKI and NSAID therapy. The primary end point, AKI, was defined according to Kidney Disease Improving Global Outcomes neonatal criteria. RESULTS: The rate of AKI for the entire cohort (n=594) was 12% (n=71). Among neonates receiving NSAIDS, 14.8% (n=44) experienced an AKI as compared to 9.1% (n=27) for those who were not exposed (relative risk, 1.6; 95% confidence interval, 1.0 to 2.6). Therefore, the attributable risk of NSAID use was 5.7% (95% confidence interval, 0.5 to 11.0). CONCLUSION: Among neonates with PDA and receiving gentamicin, NSAID therapy increases the risk of AKI by about 6%.

A bespoke management package can reduce levels of injurious pecking in loose-housed laying hen flocks.

This study investigated the protective effects of an on-farm management package designed to reduce injurious pecking (IP) in loose-housed laying hens. A systematic review of scientific literature generated 46 potentially protective management strategies. Bespoke management packages were designed for treatment flocks (TF) using these management strategies. IP in 53 TFs was compared with IP in 47 control flocks (CF) where the management package was not employed. Scoring of plumage damage (PD) and observations of gentle and severe feather pecking (GFP; SFP), and vent and cannibalistic pecking (VP) were completed, and management strategy use was recorded, at 20, 30 and 40 weeks of age. Differences between treatment and CF were examined using multilevel modelling. Compared with CF, TF employed more management strategies (P<0.001), had lower PD (P=0.003) and SFP (P=0.019). Regardless of treatment or control flock status, the more of the 46 management strategies that were employed the lower was the PD (P=0.004), GFP (P=0.021), SFP (P=0.043), mortality at 40 weeks (P=0.025), and the likelihood of VP (P=0.021). Therefore, the provision of a bespoke management package was protective against the majority of forms of IP in commercial laying hen flocks.

Prevalence of nematode infection and faecal egg counts in free-range laying hens: relations to housing and husbandry.

1. Faecal samples from 19 commercial, 65 week old free-range egg laying flocks were examined to assess the prevalence and number of parasitic nematode eggs. Data were collected to characterise the housing, husbandry, behaviour and welfare of the flocks to examine possible relationships with the egg counts. 2. Eggs of at least one genus of nematode were present in the faeces of all 19 flocks. Heterakis eggs were detected in 17 (89%) flocks, Ascaridia in 16 (84%), Trichostrongylus in 9 (47%), and Syngamus in 6 (32%). Faecal egg counts (FEC) were greatest for Ascaridia and Heterakis. 3. For each nematode genus, there was no significant difference in FEC between organic (N = 9) and non-organic (N = 10) flocks, or between static (N = 8) and mobile (N = 11) flocks. 4. FEC were correlated with a range of housing, husbandry and management practices which varied between the nematode genus and included depth of the litter, percentage of hens using the range, and number of dead hens. Statistical analysis indicated relationships with FEC that included light intensity above the feeder, indoor and outdoor stocking density, fearfulness in the shed and on the range, distance to the nearest shelter, and swollen toes. 5. None of the FEC for any of the genera was correlated with weekly egg production or cumulative mortality. 6. Although nematode FEC were highly prevalent among the flocks, the overall lack of relation to other welfare and production measures suggests that these infections were not severe.

Comparison of the welfare of layer hens in 4 housing systems in the UK.

1. The welfare of hens in 26 flocks (6 conventional cage, 6 furnished cage, 7 barn, 7 free-range) was assessed throughout the laying period using a combination of data on physical health, physiology and injurious pecking, collected by researchers on farm and during post-mortem analysis, and information submitted by producers. 2. There was an effect of housing system on 5 of the indicators recorded by researchers: gentle feather pecks given, feather damage score, proportion of hens with feather damage, proportion of the flock using perches, and faecal corticosterone. 3. Post-mortem analysis revealed several differences between housing systems in skin damage, plumage damage to the vent and abdomen, keel protrusion, bodyweight, and the proportion of hens that were vent pecked and that had old and recent keel fractures. 4. There was an effect of housing system on 5 indicators recorded by producers: proportion of egg shells with calcification spots, proportion of egg shells with blood stains, weight of hens found dead, temporal change in the proportion of egg shells with stains, and temporal change in proportion of hens found dead. 5. Each housing system had positive and negative aspects but overall, hens in barn systems had the highest prevalence of poor plumage condition, old fractures, emaciation, abnormal egg calcification, and the highest corticosterone. Hens in conventional cages sustained more fractures at depopulation than birds in other systems. Vent pecking was most prevalent in free-range flocks. The lowest prevalence of problems occurred in hens in furnished cages. 6. Although housing system had an influence on the hens' physical condition and physiological state, the high prevalence of emaciation, loss of plumage, fractures and evidence of stress is of concern across all housing systems, and suggests that the welfare of modern genotypes is poor.

Effect of ultraviolet radiation on the performance of intact male turkeys.

Ultraviolet (UV) sensitivity in birds has been shown to be intrinsically involved in the selection of mates; UV may, therefore, also play a role in the establishment and maintenance of social hierarchies in intensively housed turkeys. Cereal seeds and straw are known to reflect UV, and turkeys may use these cues for foraging and exploratory behaviors. A series of trials was conducted to see if supplementation of the photoperiod (12 h at various white light intensities) with UV radiation (0.06 to 0.16 W/m2 at floor level) and regular supplies of straw to the litter allow a better recognition of individuals within a flock, enrich the environment by the provision of new pecking material and of radiation across the whole range of avian sensitivity, and, as a consequence, reduce the incidence of injurious pecking in male turkeys that have not been beak-trimmed, detoed, or desnooded. Body weight gain, feed intake, feed conversion efficiency, and leg integrity were generally not significantly affected by UV supplementation and environmental enrichment. In contrast, the provision of UV radiation, simultaneous with a 12-h photoperiod of white light at intensities of <70 lx to 5 wk and of 10 lx to 20 wk, and the regular addition of straw to the litter, significantly reduced the incidence of culling because of injurious pecking. However, complex interactions among UV supplementation, white light intensity, and material environmental enrichment precluded a simple recommendation to solve the problem of injurious pecking.

Preliminary investigations of ultraviolet-induced markings on domestic turkey chicks and a possible role in injurious pecking.

Several gallinaceous species including domestic turkeys have the capacity for ultraviolet (UV) vision. This might function in signalling between birds, for example in individual recognition, which would suggest the presence of plumage markings visible under UV radiation. Between 1 and 22 d of age, the plumage of 17 male turkey poults (BIG6) was examined. When viewed under a conventional fluorescent white luminaire (which emits minimal UV) the birds were a uniform yellow or white according to the stage of feather emergence. However, when viewed under a lamp emitting radiation with peaks in the UV spectrum, distinct fluorescent and non-fluorescent patches were observable on several parts of the body including the wings, tail, shoulders, thighs, neck, breast and dorsal surface. This paper describes the changes in incidence, size, location and qualitative aspects of these UV-visible markings. The age at which UV-visible markings were first observed on the wings and tail corresponded closely with the age at which injuries to these sites were first caused by pecking, as reported previously. It is suggested that the 'unnatural' appearance of these markings under conventional lighting, which emits minimal UV radiation, might attract or protract injurious pecking from conspecifics.

Effects of environmental enrichment, fluorescent and intermittent lighting on injurious pecking amongst male turkey poults.

1. Under commercial and experimental conditions domestic turkeys often cause injuries to pen-mates by repeated pecking, sometimes fatally. Environmental enrichment or lighting manipulations might be used to mitigate such injurious pecking. 2. This study examined responses to 4 treatments (2 rooms/treatment) of 8 groups of 100, non-beak trimmed, non-desnooded, male domestic turkeys from 1 to 35 d of age. 3. Birds of 1 treatment were reared under conditions approximating to commercial rearing (12L:12D incandescent, Control) whereas the experimental treatments were 12L:12D incandescent plus supplemental ultraviolet radiation, straw supplementation of litter, pecking substrates and visual barriers (Enriched), 12L:12D fluorescent lighting (Fluorescent), and 2(2L:3D):2L:12D incandescent (Intermittent). 4. Compared to control birds, the incidence of injuries caused by wing or tail pecking were both lower in the Enriched but not significantly different in the Fluorescent or Intermittent. 5. Injuries caused by head pecking did not occur in the Enriched rooms but were observed in at least 1 of the rooms with Control, Fluorescent and Intermittent treatments. 6. Despite considerable environmental differences between treatments, there was remarkable consistency within each type of injurious pecking in age at which injuries were 1st recorded (wing pecking, 9.38+/-1.31 d; tail pecking, 20.43+/-2.42 d; head pecking, 27.8+/-2.13 d). The roles of feather emergence, hierarchy formation in wild turkey poults and appearance of feathers are discussed as possible explanations of these consistencies.

Time-budgets, comfort behaviours and injurious pecking of turkeys housed in pairs.

1. Large group size and high stocking density can compromise the welfare of poultry. This study, the first in a series of trials to determine the effect of these factors, examined the behaviour of turkeys under conditions in which group size and stocking density would have minimal influence, that is, when the birds were housed as pairs in pens measuring 3.0 x 3.6 m. 2. The 24 h time-budgets, frequency of comfort behaviours and incidence of injurious pecking were recorded on 12 occasions when the birds were between 4 and 22 weeks of age. 3. Over the duration of the study the proportion of time engaged in drinking or pecking other birds remained constant, but decreased for sleeping, environment pecking, wing-flapping, and running, increased for stretching, and varied throughout for feeding, standing, sitting, strutting, preening whilst standing, preening whilst sitting, and walking. 4. Some of the changes in activity were probably attributable to age effects per se. though other changes may have been related to increased musculo-skeletal weakness. 5. At 18 weeks of age, the turkeys spent a considerable proportion (30%) of time performing a sexual courtship display, strutting. Although the prevalence of this activity subsequently decreased, the likelihood of increased metabolic costs and potential for frustration indicate further investigation is warranted. 6. The turkeys behaved socially and were strongly influenced by social facilitator. 7. There were considerable differences between the behaviour of the turkeys and other common poultry species: the turkeys performed a running or frolicking behaviour and strutting, but did not exhibit other behaviours commonly observed such as dustbathing and ground-scratching whilst feeding. 8. Injurious pecking was infrequent. Only 14 bouts of behaviour likely to cause injury were recorded in 1,656 turkey-hours of continuous observation; no turkey required attention as a consequence of this behaviour. Feather pecking and cannibalism did not occur despite higher than conventional light intensities; the low frequency of injurious pecking could be attributed to the small group size/low stocking density.

Observations on the prevalence of nest-building in non-breeding TO strain mice and their use of two nesting materials.

The spontaneous performance of nest-building behaviour by non-breeding laboratory mice suggests that routinely providing nesting material might be a suitable environmental enrichment. If nesting material is to be provided routinely, this should have characteristics which are preferred, or at least accepted by a considerable proportion of the animal population; it should also be inexpensive. The present study therefore examined the prevalence of nest-building behaviour in 39 individually-housed, non-breeding, female mice, and their preferences for a commercial nesting product and a less expensive source of material (paper towels). Within minutes of the materials being placed in the cages, the mice began manipulating the paper towels. Thirty-six of the mice subsequently constructed nests during the first dark phase after the materials had been placed in the cage--the remaining three mice constructed nests during the following 48 h. The nests were usually constructed from a mixture of the two materials, though observations indicated the mice might have preferred characteristics of the inexpensive paper towels. There was a strong tendency to build nests in the same location used for sleeping prior to the nesting material being provided, and similarly, the mice were conservative in the site chosen to build a second nest after the first was removed. The most frequently chosen site for nest-building was under the feeder. Other studies have reported a high motivation for nest-building behaviour, widespread performance amongst many strains, and nest-building as a thermoregulatory behaviour by animals housed in standard laboratory air temperature. In conjunction with these findings, the present results suggest that routinely providing paper towels is an inexpensive and practical means of environmental enrichment for non-breeding, laboratory mice.

Preferences of individually housed TO strain laboratory mice for loose substrate or tubes for sleeping.

If we are to improve welfare by appropriate environmental design, it is important to determine which characteristics of prefabricated shelters are preferred by laboratory mice. Three investigations were conducted to determine the preferences of individually housed mice for shape, opacity and openness of tubes for sleeping in. During all three investigations, it was evident that the mice preferred to sleep in sawdust when this was available. The mice slept in the tubes only after the sawdust was removed, and then slept in the tubes rarely once the sawdust was replaced. Individual mice were generally consistent in their choice of tube type, even when the position was changed. However, there were no overwhelming group-preference for shape, opacity or openness of the tubes, though a short, wide tube was used more frequently than a long, or short narrow structure. Several mice performed shelter-building activities when using the tubes, indicating that either some characteristic of the tubes was unsatisfactory or that the mice were motivated to perform shelter-building activities despite the presence of a satisfactory structure. Providing pre-formed tubes might not improve welfare if mice are motivated to perform the activities of shelter-building themselves, rather than achieving the functional consequences. However, the repeated use of tubular structures for other purposes, e.g. as a refuge or latrine, indicates that providing such structures is likely to enhance the welfare of laboratory mice.

Variation in behavioural indices of fearfulness and fatigue in transported broilers.

Several behavioural measures were used to determine fearfulness and fatigue in broiler chickens subjected to fasting and/or transportation. There was considerable variability between four replicates, although measures within replicates were acceptably consistent. There was no uniform effect of fasting or transport on behaviour. The most cogent results were obtained by monitoring post-journey behaviour. In the few hours after transport, fasted and transported birds stood more than control birds which could be explained by increased food-searching behaviour and/or arousal. It is argued that the high variability between replicates indicates that considerable efforts must be made to control environmental variables in studies of behaviour after transporting chickens.