Glyphosate (GLY) is worldwide one of the most used active substances in non-selective herbicides. Although livestock might be orally exposed via GLY-contaminated feedstuffs, not much is known about possible hepatotoxic effects of GLY. As hepatic xenobiotic and nutrient metabolism are interlinked, toxic effects of GLY residues might be influenced by hepatic nutrient supply. Therefore, a feeding trial with lactating dairy cows was conducted to investigate effects of GLY-contaminated feedstuffs and different concentrate feed proportions (CFP) in the diets as tool for varying nutrient supply to the liver. For this, 61 German Holstein cows (207 ± 49 days in milk; mean ± standard deviation) were either fed a GLY-contaminated total mixed ration (TMR, GLY groups, mean GLY intake 122.7 μg/kg body weight/day) or control TMR (CON groups, mean GLY intake 1.2 μg/kg body weight/day) for 16 weeks. Additionally, both groups were further split into subgroups fed a lower (LC, 30% on dry matter basis) or higher (HC, 60% on dry matter basis) CFP resulting in groups CONHC (n = 16), CONLC (n = 16), GLYHC (n = 15), GLYLC (n = 14). Blood parameters aspartate aminotransferase, γ-glutamyltransferase, glutamate dehydrogenase, cholesterol, triglyceride, total protein, calcium, phosphorus, acetic acid and urea and histopathological evaluation were not influenced by GLY, whereas all mentioned parameters were at least affected by time, CFP or an interactive manner between time and CFP. Total bilirubin blood concentration was significantly influenced by an interaction between GLY and CFP with temporarily elevated concentrations in GLYHC, whereas the biological relevance remained unclear. Gene expression analysis indicated 167 CFP-responsive genes, while seven genes showed altered expression in GLY groups compared to CON groups. Since expression changes of GLY-responsive genes were low and liver-related blood parameters changed either not at all or only slightly, the tested GLY formulation was considered to have no toxic effects on the liver of dairy cows.

Female pigs respond sensitive both to DON and ZEN with anorexia and endocrine disruption, respectively, when critical diet concentrations are exceeded. Therefore, the frequent co-contamination of feed by DON and ZEN requires their parallel inactivation. The additive ZenA hydrolyzes ZEN while SBS inactivates DON through sulfonation. Both supplements were simultaneously added (+, 2.5 g SBS and 100 U ZenA/kg) to a control diet (CON−, 0.04 mg DON and < 0.004 mg ZEN/kg; CON+, 0.03 mg DON and < 0.004 mg ZEN/kg) and a Fusarium toxin contaminated diet (FUS−, 2.57 mg DON and 0.24 mg ZEN/kg; FUS+, 2.04 mg DON and 0.24 mg ZEN/kg). The 4 diets were fed to 20 female weaned piglets each (6 kg initial body weight) for 35 days; the piglets were sacrificed thereafter for collecting samples. Supplements improved performance and modified metabolism and hematology independent of dietary DON contamination. The mechanisms behind these changes could not be clarified and require further consideration. SBS reduced DON concentration in feed by approximately 20% and to the same extent in blood plasma and urine suggesting that no further DON sulfonate formation occurred in the digestive tract before absorbing DON in the upper digestive tract or that additionally formed DON sulfonates escaped absorption. DON sulfonates were detected in feces suggesting that unabsorbed DON sulfonates reached feces and/or that unabsorbed DON was sulfonated in the hindgut. The observed reduction rate of 20% was evaluated to be insufficient for feeding practice. Galenic form of SBS added to dry feed needs to be improved to support the DON sulfonation in the proximal digestive tract.ZenA was active in the digestive tract as demonstrated by the presence of its hydrolyzed none-estrogenic reaction products hydrolyzed ZEN (HZEN) and decarboxylated and hydrolyzed ZEN (DHZEN) both in feces, systemic circulation, and urine of group FUS+ compared to group FUS−. The presence of these hydrolysis products was paralleled by a significant decrease in high-estrogenic ZEN concentrations which, in turn, was related to a decrease in relative weights of uteri and ovaries when compared to group FUS−. Thus, ZenA was proven to be effective; both in terms of biomarkers and biological effects.

Maternal exposure to various stimuli can influence pre- and postnatal development of the offspring. This potential has been discussed for glyphosate (GLY), active substance in some non-selective herbicides. Accordingly, present study investigated putative effects of GLY residues in rations on cows and their offspring. Dams received either GLY-contaminated (GLY groups) or control (CON groups) rations combined with low (LC groups) or high (HC groups) concentrate feed proportions (CFP) for 16 weeks during mid- and late lactation and early gestation (59±4 days at beginning of GLY exposure; mean±SE). During this feeding trial, average daily GLY exposures of dams were 1.2 (CONLC), 1.1 (CONHC), 112.5 (GLYLC) and 130.3 (GLYHC) μg/kg body weight/d. After a depletion period (107±4 days; mean±SE) and calving, blood samples of dams and their calves were collected (5–345 min after birth) before calves were fed colostrum and analyzed for hematological and clinical-chemical traits, redox parameters, functional properties of leukocytes and DNA damage in leukocytes. No evidence for malformations of newborn calves could be collected. At parturition, most analyzed blood parameters were not affected by dietary treatment of dams during gestation. Significant GLY effects were observed for some traits, e.g. blood non-esterified fatty acids (NEFA) in calves. These deviations of GLY groups from CON groups likely resulted from strong time-dependent responses of NEFA levels within the first 105 minutes after birth and before colostrum intake (Spearman´s rank correlation R = 0.76, p<0.001). Additionally, significant GLY effects did not result in differences in measures that were beyond normally observed ranges questioning a pathological relevance. In summary, no evidence for teratogenic or other clear effects of GLY or CFP on analyzed parameters of dams and their newborn calves could be collected under applied conditions. However, detailed studies including GLY exposure during late and complete gestation period would be needed to rule out teratogenic effects.

The sensitivity of pigs to deoxynivalenol (DON) might be increased by systemic inflammation (SI), which also has consequences for hepatic integrity. Liver lesions and a dys-regulated gene network might hamper hepatic handling and elimination of DON whereby the way of initiation of hepatic inflammation might play an additional role. First and second-pass exposure of the liver with LPS for triggering a SI was achieved by LPS infusion via pre- or post-hepatic venous route, respectively. Each infusion group was pre-conditioned either with a control diet (0.12 mg DON/kg diet) or with a DON-contaminated diet (4.59 mg DON/kg diet) for 4 wk. Liver transcriptome was evaluated at 195 min after starting infusions. DON exposure alone failed to modulate the mRNA expression significantly. However, pre- and post-hepatic LPS challenges prompted transcriptional responses in immune and metabolic levels. The mRNAs for B-cell lymphoma 2-like protein 11 as a key factor in apoptosis and IFN-γ released by T cells were clearly up-regulated in DON-fed group infused with LPS post-hepatically. On the other hand, mRNAs for nucleotide binding oligomerization domain containing 2, IFN-α and eukaryotic translation initiation factor 2α kinase 3 as ribosomal stress sensors were exclusively up-regulated in control pigs with pre-hepatic LPS infusion. These diverse effects were traced back to differences in TLR4 signalling.

Glyphosate (GLY), the active substance in non-selective herbicides, is often found in ruminant feed. The present feeding study aimed to investigate the effects of GLY-contaminated rations and different concentrate feed proportions (CFP) on the health of fattening German Holstein bulls. Bulls were grouped by low (LC) or high (HC) CFP with (GLYLC, GLYHC) or without GLY-contaminations (CONLC, CONHC) in their rations. Intakes (dry matter, water) and body weight were documented continuously lasting over an average range from 392.2 ± 60.4 kg to 541.2 ± 67.4 kg (mean ± SD). Blood samples collected at the trial’s beginning, and after 7 and 15 weeks, were analyzed for hematological and clinical-chemical traits, functional properties of leukocytes, redox parameters and DNA damage. The average GLY exposures of 128.6 (GLYHC), 213.7 (GLYLC), 1.3 (CONHC) and 2.0 µg/kg body weight/d (CONLC) did not lead to GLY effects for most of the assessed parameters relating to animal health and performance. CFP and time displayed marked influences on most of the experimental parameters such as higher dry matter intake and average daily gain in HC compared with the LC groups. GLY effects were rather weak. However, the observed interactive effects between GLY and CFP and/or time occurring in an inconsistent manner are likely not reproducible. Finally, all animals remained clinically inconspicuous, which brings into question the physiological relevance of putative GLY effects.