Table 4.

Repeated dose studies in pigs published after 2006

Strain	Dose and animals per group	Duration/time of observation	Main effects observed	Effect level	Reference
TOPIGS‐40, cross‐bred weaned piglets (♀)	0 and 50 μg/kg diet corresponding to approx. 2.7 μg OTA/kg bw per day** ( 1 ) n = 6	30–33 days	Minor decrease in total protein and albumin in serum, increased serum ALT and triglycerides	50 μg/kg diet corresponding to approx. 2.7 μg OTA/kg bw per day** (based on biochemical changes)	Marin et al. (2016)
			Altered expression of genes involved in cellular growth/proliferation, cell death/survival, and immune function in kidney		Marin et al. (2017a)
			Altered expression of molecules involved in immune response and antioxidant self‐defence in gut (and kidney)		Marin et al. (2017b)
TOPIG hybrid [(Landrace × Large white) × (Duroc × Pietrain)] piglets (sex not specified)	0 and 250 μg/kg diet corresponding to approx. 12.5 μg/kg bw per day**; n = 5	28 days	Increase in total protein, albumin, triglycerides and creatinine in serum Decreased total antioxidant capacity in liver and kidney, decreased GPx activity in kidney Differential effects on cytokine synthesis	250 μg/kg diet corresponding to 12.5 μg/kg bw per day** (based on biochemical changes)	Marin et al. (2018)
cross‐bred ([Landrace × Yorkshire] × Duroc) piglets (sex not specified)	0, 400, 800 μg/kg diet corresponding to approx. 20 and 36 μg/kg bw per day** n = 12	42 days	Polyuria and polydipsia (400, 800 μg/kg diet) Reduced feed intake and growth performance (400, 800 μg/kg diet) Increased AST, creatinine and urea in serum (400, 800 μg/kg diet) Renal histopathological findings: Hyperchromatic nuclei and cytoplasm, nuclei atrophy, necrosis and exfoliation in proximal tubules (400, 800 μg/kg diet)	LOAEL* 400 μg/kg diet corresponding to approx. 20 μg/kg bw per day (based on reduced growth performance, renal histopathology and blood biochemistry)	Zhang et al. (2016)
	0, 400, 800 μg/kg diet corresponding to approx. 19 and 36 μg/kg bw per day** n=9	42 days	Decreased growth performance (400, 800 μg/kg diet) Renal histopathological findings: Hyperchromatic nuclei and cytoplasm, nuclei atrophy, necrosis and exfoliation in proximal tubules (400, 800 μg/kg diet) Decrease in TCR‐induced T lymphocyte viabilities in peripheral blood lymphocytes and splenocytes (400, 800 μg/kg diet) Induction of glucose regulated protein 78, p38 and ERK1/2 phosphorylation, and LC3 II and Atg5 protein expression in kidney and spleen (400, 800 μg/kg diet)	LOAEL* 400 μg OTA/kg diet corresponding to approx. 19 μg/kg bw per day (based on reduced growth performance, renal histopathology and immunological parameters)	Gan et al. (2017b)
Large‐White weaned pigs (castrated ♂)	~ 0.45 (control), 180 μg/kg diet corresponding to approx. 9 μg/kg bw per day **; n = 30	43 days	Decreased serum protein, increased levels of TNF‐α and IL‐10 in plasma Decreased capacity of whole blood to respond with cytokine expression (mRNA and protein) to ex vivo challenge with LPS	180 μg/kg diet corresponding to approx. 9 μg/kg bw per day**	Bernardini et al. (2014)
Hungarian Large White × Hungarian Landrace F1 weaned piglets (♂: ♀ = 1:1)	0, 380 – 338 μg/kg diet corresponding to approx. 14 μg/kg bw per day**; n = 12	49 days	Reduced feed consumption and daily weight gain Increased malondialdehyde in liver, decreased Glutathione peroxidase activity in liver and kidney	379.6–338.1 μg/kg diet corresponding to approx. 14 μg/kg bw per day**	Balogh et al. (2007)
Zegers hybrid (♂)	0, 300 μg/kg diet( 2 ) corresponding to approx. 9 μg/kg bw per day***; n = 6	30 days	Decrease in serum glucose and total protein, increase in serum creatinine and urea in OTA‐treated pigs on day 10, 20 and 30 as compared to control group without indication of time point (i.e. lack of time‐matched controls)	300 μg/kg diet( 2 ) corresponding to approx 9 μg/kg bw per day***	Pleadin et al. (2012)
Landrace × Bulgarian white (♂: ♀ = 1:1)	0, 500 μg/kg diet corresponding to approx. 15 μg/kg bw per day***; n = 6	3 months	Macroscopic kidney lesions Renal histopathological changes: cloudy swelling, granular or vacuolar degeneration and desquamation involving proximal tubules Slight degenerative changes in the duodenal or jejunal mucosa Increased serum creatinine and urea; increased ALT and AST Disturbance in humoral immune response	500 μg/kg OTA corresponding to approx. 15 μg/kg bw per day***	Stoev et al. (2012)

ALT: alanine aminotransferase; AST: aspartate aminotransferase; LOAEL: lowest observed adverse effect level; NOAEL; no observed adverse effect level; n: number; PCT: proximal convoluted tubular; GPx: Glutathione peroxidase; TCR: T‐cell receptor.

^*NOAEL/LOAEL not explicitly reported but derived from data presented in study.

^**Calculated using parameters (bw, feed intake) provided in the paper.

^***Calculated using default values provided in EFSA Scientific Committee (2012a), EFSA FEEDAP Panel (2012), WHO/IPCS (2009).

¹The experimental diet also contained low levels of fumonisin B₁ (88 μg/kg corresponding to approx. 5 μg/kg bw per day), which is below the NOAEL for fumonisins in pigs.

²Unclear reporting of route of administration: ‘The experimental group was treated with feed contaminated with 300 μg OTA/kg (300 ppb). OTA as a pure chemical (standard) was mixed with lactose and distributed in gelatin capsules that were applied directly into pig mouth.’