Current concepts of Harm-Benefit Analysis of Animal Experiments - Report from the AALAS-FELASA Working Group on Harm-Benefit Analysis - Part 1.

International regulations and guidelines strongly suggest that the use of animal models in scientific research should be initiated only after the authority responsible for the review of animal studies has concluded a well-thought-out harm-benefit analysis (HBA) and deemed the project to be appropriate. Although the process for conducting HBAs may not be new, the relevant factors and algorithms used in conducting them during the review process are deemed to be poorly defined or lacking by committees in many institutions. This paper presents the current concept of HBAs based on a literature review. References on cost or risk benefit from clinical trials and other industries are also included. Several approaches to HBA have been discovered including algorithms, graphic presentations and generic processes. The aim of this study is to better aid and harmonize understanding of the concepts of 'harm', 'benefit' and 'harm-benefit analysis'.

Recommendations for Addressing Harm-Benefit Analysis and Implementation in Ethical Evaluation - Report from the AALAS-FELASA Working Group on Harm-Benefit Analysis - Part 2.

International regulations and guidelines strongly suggest that the use of animal models in scientific research should be initiated only after the authority responsible for the review of animal studies has concluded a well-thought-out harm-benefit analysis (HBA) and deemed the project to be appropriate. The AALAS-FELASA working group on HBA has performed a literature review and based on this review, proposed a method for HBA. Examples of the working group's approach are included in this report.

Impact of social isolation and enriched environment during adolescence on voluntary ethanol intake and anxiety in C57BL/6J mice.

This study was designed to determine the impact of an enriched environment in a previously established stress model of isolation during early development that induces high alcohol (ethanol) self-administration. The study was conducted with male and female C57BL/6J mice housed in isolation or in groups that were either provided or withheld enrichment during adolescence. The impact of these housing conditions was assessed during adulthood by measuring weight gain, quantifying voluntary ethanol intake, measuring plasma corticosterone levels, and assessing anxiety-like behavior. Results showed that, regardless of sex, mice that were single-housed during adolescence showed a significant increase in voluntary ethanol intake, which was not observed in isolated mice that were provided with nesting material during adolescence (compared to group-housed non-enriched control group). Basal corticosterone was not affected by housing, enrichment conditions, or sex. Corticosterone levels did not relate to levels of voluntary ethanol intake. However, corticosterone levels were higher after three weeks of ethanol intake. Surprisingly, mice that were group-housed during adolescence showed higher levels of anxiety-like behavior in the light/dark test. Overall, these results indicate that housing conditions during a critical developmental period can significantly modulate voluntary ethanol intake later in life.

Effects of housing density on weight gain, immune function, behavior, and plasma corticosterone concentrations in BALB/c and C57BL/6 mice.

The Guide for the Care and Use of Laboratory Animals contains recommended housing densities for rodent species that are commonly used by the scientific community. However, at the time of the Guide's publication, housing density recommendations were based heavily on the professional judgment of qualified scientists. Some scientists therefore question whether rodents can be housed at greater densities, whereas others wonder whether the space currently provided for rodents is sufficient. The present study was designed to determine the effect of housing adult female BALB/c- and C57BL/6-mice in standard 75-in(2) (484-cm(2)) ventilated cages at various housing densities (n = 2, 5, and 10 mice/cage). Measures of weight gain, plasma corticosterone, behavior, and immune parameters were evaluated at 7, 28, and 70 d after housing allocation. Housing BALB/c mice at 10/cage had negative effects on weight gain, corticosterone, behavior, and immune parameters. Housing C57BL/6 mice at 10/cage did not affect immune function or weight gain, although behavior and corticosterone showed statistical trends implying a negative effect Differences associated with housing densities of 2 and 5 mice/cage were less robust for all variables measured. We conclude that housing female BALB/c mice at 10 mice/cage (that is, at twice the Guide-recommended density) affects their physiology. We also conclude that mice vary in their responses in the parameters measured. These observations support the conclusion that it will be extremely challenging to scientifically determine an optimal cage density standard that can be uniformly applied across all mouse strains.

Field studies and the IACUC: protocol review, oversight, and occupational health and safety considerations.

Field studies involving animals, like other institutional research endeavors, are regulated and evaluated by an IACUC to insure that the protocols employed in those studies are consistent with the most humane care and use of animals. Unlike many other on-site research projects, however, field studies present unique logistical and other challenges to IACUC evaluation. The authors explore many of these challenges, including the special protocol considerations and idiosyncratic occupational health and safety concerns characteristic of field-study reviews.

A renewed look at laboratory rodent housing and management.

Since its publication in 1996, the Guide for the Care and Use of Laboratory Animals (National Research Council, Washington DC, National Academy Press) has become a primary source of information for institutional animal care and use committees (IACUCs) and research facility managers. In the ensuing years, recommendations relating to laboratory animal care have evolved in response to new scientific information and use of new technology such as ventilated caging. In this article, recent publications are examined to determine the potential impact of new scientific evidence on current practices for the housing and care of laboratory rodents. The discussion points out recent advances in technology and new knowledge of the conditions for the housing of various laboratory rodents, including cage space, single versus group housing, ventilated caging systems, thermoregulation, bedding materials, and enrichment. This new information is provided to aid IACUCs and facility managers in making decisions regarding the housing and care of laboratory rodents.