Identification of flunixin glucuronide and depletion of flunixin and its marker residue in bovine milk.

Residues of flunixin [and its marker residue 5-hydroxyflunixin (5OHFLU)] were determined in milk from cows that intravenously received therapeutic doses of the drug. The samples were collected during each milking (every 12 h) for six consecutive days, and concentrations of flunixin and its metabolites were determined by the method with and without enzymatic hydrolysis (beta-glucuronidase). The highest flunixin concentration in milk was observed 12 h after dosing (2.4 ± 1.42 µg/kg, mean ± SD). Flunixin concentrations in the samples determined with enzymatic hydrolysis were significantly higher (P < 0.05), which suggests the transfer of flunixin glucuronide to the milk. Additionally, unambiguous identification of flunixin glucuronide in the bovine milk was performed with linear ion-trap mass spectrometry. The 5OHFLU concentrations analyzed without enzymatic hydrolysis (22.3 ± 16.04 µg/kg) were similar to this obtained with enzymatic hydrolysis. Flunixin and 5OHFLU concentrations dropped below the limits of detection at 48 h after last dosing.

Pharmacokinetics of flunixin in mature heifers following multiple intravenous administration.

The pharmacokinetics of flunixin meglumine was determined after its multiple (altogether 4 doses at 24-hours intervals) intravenous administration at a dose of 2.2 mg/kg body weight in six mature clinically healthy heifers. Plasma flunixin and its metabolite 5-hydroxyflunixin concentrations were analyzed with high-pressure liquid chromatography using an assay with a lower limit detection of 0.03 microg/ml for both substances. Plasma concentrations versus time curves were described by a two compartment open model. Mean plasma flunixin concentrations were similar on day 1 and 4, and than rapidly decreased (within 2 hours) from initial concentrations higher than 10 microg/ml to the concentrations lower than 1 microg/ml. The distribution phase of flunixin was short (t0.5 alpha = 0.29 +/- 0.16 and 0.18 +/- 0.04 on day 1 and 4, respectively) and the elimination phase was more prolonged (t0.5 beta = 3.30 +/- 0.60 and 3.26 +/- 0.22 on day 1 and 4, respectively). The mean residence time of flunixin was similar on day 1 (1.83 +/- 0.83) and 4 (1.88 +/- 0.46), and for 5-hydroxyflunixin this parameter was insignificantly (P > 0.05) higher on day 1 (5.49 +/- 2.22) as compared to that found on day 4 (3.99 +/- 2.17). The clearance of flunixin was similar on both examined days (0.23 +/- 0.12 on day 1 and 0.31 +/- 0.15 on day 4), and for 5-hydroxyflunixin was insignificantly (P > 0.05) lower on day 1 (2.37 +/- 1.21) as compared to that determined on day 4 (3.23 +/- 1.06). Our data indicate that multiple administration of flunixin did not alter significantly the parent drug and its metabolite concentrations in plasma, however may cause some small changes in pharmacokinetic parameters.

Studies on the embryotoxic and teratogenic effects of Tolpa Peat Preparation.

Neither embryotoxic nor teratogenic effects were observed in hamsters and rats after administration of Tolpa Peat Preparation (TPP) in doses of 5 and 50 mg/kg daily. Some maternal toxicity in rats and some embryotoxic effect in hamsters were recorded after the highest dose of TPP (250 mg/kg daily).

Occurrence of mycotoxins in animal feeds.

A total of 1120 grain samples of oats, wheat, rye, barley, and maize, delivered for processing of mixed feeds for animals, were collected during the years 1975 to 1979 from commercial feed mills located throughout Poland. In addition, 625 samples of the commercially mixed feeds and protein concentrates were collected during 1976. For the mycotoxin survey, 751 laboratory samples were chosen at random and analyzed. When applying confirmatory tests neither aflatoxins B1, B2, G1, G2 nor sterigmatocystin, zearalenone, or ochratoxin B were found to be present in any of the samples of barley, wheat, rye, or oats. Aflatoxins were detected in about 4% of the maize samples. The presence of ochratoxin A in the range of 2 to 200 micrograms/kg was evident in 9% of the grain samples. The commercially mixed feeds were found to be more contaminated with mycotoxins than were the grains. The aflatoxins were confirmed in about 13% of the samples of mixed feeds. After the preliminary multimycotoxin analysis, out of 42 feed samples that could be suspected of containing ochratoxins, 32 failed to prove their presence. Similarly, out of 27 suspected feed samples, zearalenone was found only in one (0.5%) sample. The lowest percentage of samples contaminated with mycotoxins was found in poultry mixed feeds (4%). The highest contamination occurred among the samples of swine rations, where 17% of the samples contained aflatoxins and 13% ochratoxins. The protein concentrates contained only aflatoxins. Out of 31 analyzed samples, aflatoxins were detected in 19 (61%) in concentrations ranging from 5 micrograms/kg to 500 micrograms/kg. In one sample, aflatoxin concentration (B1 + B2) reached 1140 micrograms/kg. Practical implications of the results are discussed in relation to animal and human safety.

Teratological evaluation of Ukrain in hamsters and rats.

The compound Ukrain, containing thiophosphoric acid alkaloid derivatives from the plant Chelidonium majus L., was given intramusculary (i.m.) on days 6-11 of gestation to hamsters and on days 6-15 of gestation to rats in doses of 0.1, 1.67 and 28 mg/kg daily. No clinical signs of toxicity were found in treated animals and no teratogenic effect could be noted in either species. Such parameters as the number of corpora lutea, implantation sites, pre and post-implantation losses, number of live foetuses per litter, placental weight, foetal weight and crown-rump length were not significantly different between the Ukrain treated rats and the controls. Slight embryotoxic effects (increased post-implantation losses) and in consequence decreased number of average litter size were noted in hamsters exposed to Ukrain at doses which were otherwise not embryotoxic to rats.

Zinc status in women with premature rupture of membranes at term.

Zinc concentrations were measured by atomic absorption spectrometry in whole blood, scalp hair, pubic hair, and colostrum from patients at term with and without premature rupture of membranes (PROM). A maternal zinc index was established for each patient, expressed as an average ranking of the four determinations. The mean +/- SD value of the maternal zinc index in patients with PROM was significantly lower than in patients without this complication (4.33 +/- 1.18 versus 5.97 +/- 1.39, respectively; P = .0002). The inverse relationship between maternal zinc index and parity was statistically significant (r = -0.61; P = .04). These results suggest that the subnormal tissue zinc content in pregnancy may play a role as a causative factor in PROM at term.

Tissue deposition and passage into eggs of ochratoxin A in Japanese quail.

Laying Japanese quail (Coturnix coturnix japonica) were given single oral doses of 0, 1, 5, and 20 mg of ochratoxin A (OA) per kg of the body weight. After 6, 12, and 24 hours and 2, 3, 4, 5, 6, and 7 days an appropriate number of birds was sacrificed and OA in blood, muscles, liver, kidney, abdominal yolks, and collected eggs was measured. The highest concentration of OA was found in kidneys and the lowest in muscles. Four days following the application, OA could still be detected in kidney, liver, muscles, yolk, and eggs, although even after six days traces of OA were found in the muscles of birds given 20 mg/kg.

[Usefulness of male golden hamsters for experimental reproductive pathology]. / Przydatnosc samców chomika zlocistego do badan w zakresie patologii rozrodu.

Seventy two male Golden hamsters were maintained in normal laboratory conditions (12h light-dark cycle, 20 +/- 2 degrees C) for the annual cycle experiment. Every month 6 animals were sacrificed and testis weight, cauda epididymis weight, caudal sperm number, sperm morphology and body weight were determined. The period of high gonadal activity was found to be from March to the end of July. In September reproductive activity decreased and the low activity period, with azoospermia in some animals, lasted till the end of January. This annual reproductive cycle, shown for the male Golden hamsters, should be taken into consideration when designing new experiments and interpreting their results.

Women in dental surgeries: reproductive hazards in occupational exposure to metallic mercury.

Eighty-one women (45 dentists and 36 dental assistants) occupationally exposed to metallic mercury underwent a toxicoclinical examination. Total mercury lebels (TMLs) were determined in scalp and pubic hair by cold vapour AAS. Furthermore a detailed questionnaire study was made concerning adverse reproductive events. TMLs in the hair of the exposed women examined exceeded significantly those determined in the hair of 34 controls not exposed to mercury. All exposed women had continued working during pregnancy. There was a significant, positive association between TMLs in the hair of exposed women and the occurrence of reproductive failures in their history. The relation between TMLs in the scalp hair and the prevalence of menstrual cycle disorders was statistically significant. These findings indicate that dental work could be another occupational hazard with respect to reproductive processes.

Hair trace metal concentration of pregnant women at term in comparison with blood and milk levels.

The concentrations of Fe, Cu, Zn and Pb were determined by means of AAS in the scalp hair (SH) and pubic hair (PH) as well as in maternal blood (MB), breast milk (BM) and cord blood (CB) taken from 104 pregnant women and their neonates. SH values of all studied metals correlated with strong statistical significance with their PH levels. Significant correlations were found between maternal Fe-PH and neonatal body length (r = 0.271) as well as between Fe-SH and placental weight (r = 0.168). The age of examined women was found to correlate negatively with Cu-SH values as well as with Zn-SH (P less than 0.05). The inverse relationship between Zn-PH and the parity of examined women was established to be statistically significant (P less than 0.001). The usefulness of hair analyses in assessing trace metal status of a pregnant woman is discussed.

Mercury in neonatal scalp hair.

Total mercury levels (TML) were determined in 141 samples of maternal head and pubic hair and neonatal scalp hair. The mean mercury contents of maternal head and pubic hair were 1.88 and 1.10 mg kg-1, respectively, while the mean TML of neonatal hair was 0.11 mg kg-1. A statistically significant correlation was found between TMLs in neonatal and maternal hair. Significant inverse correlation was observed between the mercury concentration in the hair of a newborn and its birth weight. Reported findings provide evidence that the neonatal scalp hair mercury level may be a useful indicator of intrauterine exposure to mercury.

Occurrence and formation of nitrosamines in animal feeds.

A total of 465 samples of ingredients of animal feeds (fish meal, antarctic krill meal, experimental silage containing 40% dried animal wastes) and complete mixed feeds and protein concentrates were analysed for nitrate and nitrite content in the period 1973-78. Over 62% of the samples contained nitrates in concentrations ranging from 1 to 1020 mg/kg, and 6% contained 1-15 mg/kg of nitrites. After a preliminary survey, the samples having the highest levels of nitrate, nitrite and amines were selected and analysed for volatile N-nitrosamines. Of 171 selected samples, 40% were found to contain N-nitrosodimethylamine in the range of 0.003 to 0.417 mg/kg. No statistically confirmed correlation between concentrations of nitrates or nitrites and nitrosamines could be demonstrated. Large amounts of dimethylamine, ranging from 110 to 1765 mg/kg, were found in all samples of krill meal. Incubation of krill meal and fish meal with nitrite, under conditions similar to those existing in the animal stomach, resulted in the formation of substantial amounts of NDMA. The occurrence of N-nitrosamines in feeds and their possible formation in vivo from precursors present in feeds seems to be an important problem from the hygienic standpoint, because of possible "carry-over" to tissues, milk and eggs.