This study investigated the effect of food or water deprivation on the pharmacokinetics of paracetamol in 30 Holstein-Friesian preruminant calves (10 controls, 10 food withheld and 10 water-deprived) aged 24–25 days. Control calves were given paracetamol at 24–25 days and again at 28–29 days of age. In the food withheld and water-deprived calves paracetamol studies were performed before and after 4 days of food or water deprivation. In the control group there were no significant differences in pharmacokinetic parameters for paracetamol in 24–25 and 28–29-day-old calves. Witholding food for 4 days was associated with an increase in the mean residence time (MRT) of paracetamol (P < 0.01). When food was withheld total body clearance (ClB) of paracetamol was significantly decreased (P < 0.05). The volume of distribution (V(ss)) was not significantly altered. Similarly, water deprivation was associated with a significant increase in MRT and significant decrease in ClB of paracetamol (P < 0.01). The V(ss) was not significantly altered. Food or water deprivation also influenced the formation of major metabolites (glucuronide and sulphate) of paracetamol. It is concluded that food or water deprivation may impair the elimination drugs that undergo metabolism by UDP-glucuronyltransferase and sulphotransferase in cattle.

Among oral delivery systems, oil in water nano-emulsions (O/W NEs) are of particular interest to improve pharmacokinetics of lipophilic compounds. Recently, we have implemented a successful strategy to improve O/W NEs stability, based on a polymeric coating on an oil core, namely secondary O/W NEs, through the use of pharma grade formulations. However, in the field of food supplements, food grade materials are the top choice since they combine safety and cost effectiveness. Here, we have replaced pharma grade (PG) with food grade (FG) materials in the preparation of the polymer coated O/W NEs, and performed a comparative study between the two formulations to assess the FG one. At the same time, in order to provide formulations with enhanced mucus-adhesion to the intestinal barrier, secondary O/W NEs were prepared by adding thiol groups to chitosan (Ct) via a simple non-covalent procedure based on N-acetyl-cysteine (NAC) salification, thus easily implementable to a food supplement formulation. PG and FG formulations, in different materials combinations, were prepared and physico-chemically characterized (DLS, ¹H NMR, ITC, CRYO-TEM) showing similar behaviour. FG formulations (NEs, Ct-NEs and Ct-NAC-NEs) loaded with curcumin were prepared and compared with the free drug in terms of drug bioaccessibility through the INFOGEST protocol confirming improved bioaccessibility. Very interestingly, by comparing mucus-adhesion properties of the two polymeric coatings (Ct and Ct-NAC) within an intestine on chip device able to mimic the complex intestinal functions, a significant enhancement in the mucus-adhesive properties of the proposed novel Ct-NAC-NE formulation was observed with respect to Ct due to the presence of thiol groups. Nonetheless, in-vivo assays are required as a final assessment of the proposed system.

Carp (Cyprinus carpio L.) were exposed to nitrofen (NIP) by different routes (via water or food) to compare bioaccumulation parameters and tissue distribution. The bioconcentration factor of NIP was 5,100, and the lipid-corrected biomagnification factor was 0.137. Growth-corrected elimination half lives were 2.1–3.0 days via aqueous exposure and 2.7–2.9 days via dietary exposure. From either uptake route, the tissue distribution of NIP was highest in the head, followed by muscle, viscera, dermis, digestive tract and hepatopancreas, which was highly correlated with the tissue lipid content. We conclude that the uptake route has no influence on tissue distribution of NIP and that the accumulation potential in tissues depends on the lipid content.

The ability of 17α-ethinylestradiol (EE2) to elevate vitellogenin levels were investigated in male flounder Platichthys flesus and vitellogenin concentrations in flounders from the Danish coastal environment were determined. Male flounders were exposed to 17α-ethinylestradiol (EE2) via food or water. Average vitellogenin concentrations in the control fish ranged between 25 and 100 ng mL−1. Exposure to 5.1, 8.1 and 16.8 ng EE2 L−1 in water and 500 and 5000 ng EE2 kg−1 body weight (bw) every second day in the food increased the plasma vitellogenin concentration in a concentration and time dependent manner, whereas exposure to 2.7 ng EE2 L−1 in water for 21 d and 5 and 50 ng EE2 kg−1 bw for 12 days in the food did not. EE2 could be detected in liver and testes (but not in muscle) after exposure to 8.1 and 16.8 ng EE2 L−1 in the water and 5000 ng EE2 kg−1 bw in the food; the highest concentration was 6 ng g−1 wet weight in liver. The majority of the male flounders collected from nine coastal Danish sites from 1999 to 2004 had vitellogenin concentrations below 100 ng mL−1, and only at two sites moderate estrogenic inputs were indicated.

Published studies in which rats were exposed to CdCl2 in standard chow or dnnking water were analyzed to compare the relative bioavailability of cadmium from the two media. Relative bioavailability was assessed from estimates of the rate of accumulation of cadmium in kidney cortex or liver. Data were grouped into tiers based on study design and reponing of data: Tier 1, identical experimental protocols and dosage can be estimated: Tier 2, very similar or identical protocols and dosage can be estimated: Tier 3, protocols may differ and dosage can be estimated; and Tier 4, protocols may differ and dosages cannot be estimated (but concentration of cadmium in food or water is reponed). Tiers were nested, such that Tier 4 contained all relevant studies; Tier 3 included data sets from Tiers 1 and 2: and Tier 2 included the data set from Tier 1. Data within Tiers 1, 2, and 3 were subjected to a linear regression analysis with dosage as the independent variable and tissue accumulation rate as the dependent vanable to determine whether bioavailability of cadmium was significantly different based on medium of administration. The results of this analysis show the following: (1) In rats receiving food and drinking water ad libitum, the bioavailability of cadmium in drinking water is not significantly different (P > 0.05) from the bioavailability of cadmium in food when dosages are less than 4 mg/kg body wt/day. (2) Cadmium decreases food and water consumption: therefore, assessments of relative bioavailability should be made based on actual dosage rather than exposure levels. (3) Diet composition and status of the gastrointestinal tract are probably a more important determinant of the bioavailability of cadmium than is the exposure medium. (4) Studies of the effect of total diet composition on bioavailability of cadmium may be more relevant than are studies of the effect of the exposure medium. It is concluded from this analysis that the bioavailability of cadmium in food is not different from that in water when diet is provided ad llbltum. Therefore, we recommend that distinct RfDs for cadmium in food and dnnking water should not be based on the assumption that the bioavailability of cadmium in drinking water is greater than that of cadmium in food.