Table 1.

Prominent safety considerations related to human and animal health

Potential harm	Example hazards	Assessment Parameters*
Increased disease transmission	Increased abundance of vector mosquitoes	Fitness components including15:
		Growth rate
		Mating success
		Fecundity
		Adult, egg, or larval survival
		Environmental tolerances
	Increased vectorial capacity	Host seeking and biting activity15
		Vector competence* (Plasmodium or other pathogens carried by Anopheles gambiae)
		Change in temperature tolerance that could affect environmental niche or range
	Reduced control capability	Insecticide resistance*
Increased direct pathology	Increased allergenicity	Known allergenic sequences expressed by construct; construct-encoded proteins detected in saliva
	Increased toxicity	Standard toxicity test on construct-encoded proteins
	Increased parasite virulence (population replacement)96	Genotypic or phenotypic changes in parasites after passage through gene drive mosquitoes†

^*Changes to be assessed in comparison to local wild-type mosquitoes of the same genetic background.

^†This would best be performed with gametocytes collected from the field testing site to reflect the diversity of parasite strains circulating at the location and will not predict the evolutionary consequences of ongoing interactions of the parasite with the mosquito and vertebrate host over time.