D. Impact on animal wellbeing
D.1. Identify all factors and procedures that may adversely impact an animal’s wellbeing. (I think this is a drop down list. I may not have everything necessary included here).
Procedure Risk Factor
Blood/Body fluid collection Volume
Blood/Body fluid collection Frequency
Drug treatments Local and systemic effects
Drug treatments Frequency/total no. per animal
Tumour/Neoplasia induction Endpoint
Toxicology Substance
Toxicology Volume
Toxicology Endpoint/duration
Anaesthesia Induction – drug, dose, route
Anaesthesia Maintenance – drug, dose, route
Housing Duration held
D.2. for each factor identified – how to minimise adverse impact
Blood collection – volume/frequency: Blood will be collected at weekly intervals from the tail vein to a volume of no more than 0.14 mL, typically the volume collected in an efficacy study will be 0.03 mL. Treatments – local and systemic effects/frequency: as the drugs tested are initially unknown, preliminary toxicity testing is carried out to determine the MTD of the proposed schedule. Toxicity testing is performed on non-leukaemia bearing mice; we occasionally observe greater toxicity in engrafted mice. If the observed weight loss is greater than 15%, we reduce the drug dose (initially down to 75% of the MTD, further if necessary). PPTC will inform us if a drug we are testing is an antibody based compound. In these cases we will pre-treat mice in efficacy studies with acetaminophen and promethazine in order to minimise any hypersensitivity reaction to the antibody. The use of organic solvents and other known toxic compounds as vehicles for the drugs will be minimised or avoided completely where possible. Alternating injection sites will minimise local effects (e.g. left side then right side of abdomen for daily i.p. injections). Neoplasia induction – endpoint: Leukaemia will be monitored weekly by assessing levels of human cells in peripheral blood (even when mice are being imaged weekly, the monitoring of peripheral blood levels of leukaemia will continue weekly). Engraftment levels of 25% will be considered an event and the animal culled. At this stage of engraftment none of the xenografts we use induce morbidity in the mice. For cell stock expansions, with the goal …show more content…
the separation of a bully from the remaining cage mates). The maximum holding times are set for each experimental type, i.e. 20 weeks for efficacy studies, up to 52 weeks for combination efficacy studies and the primary engraftment of patient biopsy samples. Environmental enrichment is provided by the addition of paper streamers (Alpha Twist) to the cage to allow for normal nesting behaviours and a transparent red igloo as a shelter/hiding place. Additionally sunflower seeds are given once per week as a nutritional supplement to the normal chow, but also as a source of enrichment that encourages species specific behaviours.
D.3.
For all experiments within the scope of this application there is an endpoint limit of 20% weight loss from the beginning of the experiment to ensure the animal’s well-being is not compromised. Additionally the threshold of event (25% human CD45+ cells) in the peripheral blood is set to allow the completion of efficacy experiments without extending the morbidity associated with leukaemia progression.
D.4. experiments with the potential for high impact on welfare
Toxicity testing, leukaemia engraftment and drug efficacy evaluation can potentially be high impact studies. There is also an expected incidence of thymoma and lymphoma in the NSG strain (could be up to 50% by 8.5 months of
D.1. Identify all factors and procedures that may adversely impact an animal’s wellbeing. (I think this is a drop down list. I may not have everything necessary included here).
Procedure Risk Factor
Blood/Body fluid collection Volume
Blood/Body fluid collection Frequency
Drug treatments Local and systemic effects
Drug treatments Frequency/total no. per animal
Tumour/Neoplasia induction Endpoint
Toxicology Substance
Toxicology Volume
Toxicology Endpoint/duration
Anaesthesia Induction – drug, dose, route
Anaesthesia Maintenance – drug, dose, route
Housing Duration held
D.2. for each factor identified – how to minimise adverse impact
Blood collection – volume/frequency: Blood will be collected at weekly intervals from the tail vein to a volume of no more than 0.14 mL, typically the volume collected in an efficacy study will be 0.03 mL. Treatments – local and systemic effects/frequency: as the drugs tested are initially unknown, preliminary toxicity testing is carried out to determine the MTD of the proposed schedule. Toxicity testing is performed on non-leukaemia bearing mice; we occasionally observe greater toxicity in engrafted mice. If the observed weight loss is greater than 15%, we reduce the drug dose (initially down to 75% of the MTD, further if necessary). PPTC will inform us if a drug we are testing is an antibody based compound. In these cases we will pre-treat mice in efficacy studies with acetaminophen and promethazine in order to minimise any hypersensitivity reaction to the antibody. The use of organic solvents and other known toxic compounds as vehicles for the drugs will be minimised or avoided completely where possible. Alternating injection sites will minimise local effects (e.g. left side then right side of abdomen for daily i.p. injections). Neoplasia induction – endpoint: Leukaemia will be monitored weekly by assessing levels of human cells in peripheral blood (even when mice are being imaged weekly, the monitoring of peripheral blood levels of leukaemia will continue weekly). Engraftment levels of 25% will be considered an event and the animal culled. At this stage of engraftment none of the xenografts we use induce morbidity in the mice. For cell stock expansions, with the goal …show more content…
the separation of a bully from the remaining cage mates). The maximum holding times are set for each experimental type, i.e. 20 weeks for efficacy studies, up to 52 weeks for combination efficacy studies and the primary engraftment of patient biopsy samples. Environmental enrichment is provided by the addition of paper streamers (Alpha Twist) to the cage to allow for normal nesting behaviours and a transparent red igloo as a shelter/hiding place. Additionally sunflower seeds are given once per week as a nutritional supplement to the normal chow, but also as a source of enrichment that encourages species specific behaviours.
D.3.
For all experiments within the scope of this application there is an endpoint limit of 20% weight loss from the beginning of the experiment to ensure the animal’s well-being is not compromised. Additionally the threshold of event (25% human CD45+ cells) in the peripheral blood is set to allow the completion of efficacy experiments without extending the morbidity associated with leukaemia progression.
D.4. experiments with the potential for high impact on welfare
Toxicity testing, leukaemia engraftment and drug efficacy evaluation can potentially be high impact studies. There is also an expected incidence of thymoma and lymphoma in the NSG strain (could be up to 50% by 8.5 months of