Table 10.

Health outcome categories (HOCs) and related endpoints of the three systematically appraised animal studies subjected to WoE analysis

Health outcome categories (HOCs)	Endpoints
General toxicity	Clinical signs; body weight; feed intake; feed efficiency (body weight gain/feed consumed); water intake; clinical chemistry; ophthalmoscopic examination
Haematotoxicity	Haematological parameters (haemoglobin, packed cell volume (PCV), red blood cells (RBCs) white blood cells (WBCs), differential WBCs count, thrombocytes, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC))
Liver toxicity	Liver weight; macro‐ and histopathology of liver; clinical chemistry
Nephrotoxicity	Kidney weight; macro‐ and histopathology of kidney; urinalysis; clinical chemistry
Other organ toxicity (a)	Weight and macro‐ and histopathology and of brain, caecum and testes and other organs (b)
Developmental toxicity	Uterus weight; ovaries weight; fertility index; gestation index; number of corpora lutea; number implantation sites; early and late resorptions, pre‐ implantation loss, post‐implantation loss, number of dead foetuses; number of live foetuses; sex ratio; placenta weight (foetuses); fetal weight, fetal external, skeletal and visceral abnormalities

^(a)The organs included for assessment are those reported in the evaluated studies on neohesperidine dihydrochalcone, but will vary for other sweeteners depending on the included study types.

^(b)Relevant tissues and organs that are examined in standard subchronic toxicity studies, other than the ones already explicitly mentioned in the table (e.g. OECD TG 408, 1998, Section 35 for repeated dose 90‐day oral toxicity study in rodents).