[The enteral absorption of iron (II) from humic acid-iron complexes in suckling piglets using radiolabeled iron (59Fe)]. / Untersuchungen zur enteralen Resorption von Eisen (II) aus Huminsäure-Eisen-Komplexen beim Saugferkel mit Hilfe radiomarkierten Eisens (59Fe).

Bioavailability of iron (II) bounded as a chelate to macromolecular humic acids was investigated in two different concentrations using retention rates of 59Fe in piglets (age: 24 h). Investigations period was from 3 hrs. to 21 days following application. 21 days after a single oral application of the humic-acid-iron-complexes, 25% of the total Fe was detected in the animal, distributed in the erythrocytes (80%), muscles and bones (8% respectively) and liver (4%). For the first time in veterinary medicine these results enable a combined therapy of enteric and iron-deficiency syndrome by using only one drug. Recommendation for dosing is provided.

[The herbicide propachlor--14 C synthesis, toxicologic problems and methodology studies on the determination of residues in corn, potatoes, water and soil]. / Zum Herbizid Propachlor--14C-Synthese, toxikologische Fragen sowie methodische Untersuchungen zur Rückstandsbestimmung bei Mais, Kartoffeln, Wasser und Boden.

Using the synthesized agent propachlor (N-isopropyl-2-chloroacetanilid) labelled with 14C, methodical investigations revealed an extremely high steam volatility not being assumed before because of the low vapour pressure. The method of steam distillation basing on this fact is of universal application to the processing of maize, potatoes, water, and soil, in which propachlor could be quantitatively determined by gas chromatography with a detection sensitivity of 0.02 ppm. Furthermore, this methods allows a simple purification of the raw product of synthesis containing impurities up to 20%. Propachlor codistilled with steam had a purity of more than 99%. Possibly, the high steam volatility of propachlor could have economic and toxicological consequences as to its application (volatilization in the open air with a high atmospheric humidity along with high temperatures). Therefore, an investigation of the steam volatility in the general screening programme for new agents is to be recommended in addition to the usual investigations of steam pressure.

A comparative study of guanine N7-alkylation in mice in vivo by the organophosphorus insecticides trichlorphon, dimethoate, phosmet and bromophos.

Following intraperitoneal administration to male mice (strain AB Jena/Halle) of 14C-methyl-labelled trichlorphon, dimethoate, phosmet and bromophos, 10-20 Ci/mol, in dosages of 0.06-0.55 mmol/kg, DNA from liver and kidneys was analyzed for 14C in N-7 methylguanine (7-MeG). The extents of methylation were in the range of 5-10 mumol 7-MeG/mol guanine for trichlorphon and dimethoate and of 0.2-0.4 for phosmet and bromophos, for high doses, respectively Excretion half-lives of 7-MeG were differing between trichlorphon (5 hrs, high dose, and 15-17 hrs, low dose) and dimethoate (23-160 hrs, high dose). The extents of methylation at 0-6 of guanine were estimated to be around 0.01 mumol 0-6 MeG/mol guanine for high doses of organophosphates of sufficient water solubility. Factors associated with the partition of organophosphates in mammalian systems are useful for estimating DNA attack by organophosphates in mammals in vivo.

Activity of organophosphorus insecticides in bacterial tests for mutagenicity and DNA repair--direct alkylation versus metabolic activation and breakdown. II. O,O-dimethyl-O-(1,2-dibromo-2,2-dichloroethyl)-phosphate and two O-ether derivatives of trichlorfon.

The following organophosphates were tested for their ability to induce DNA damage in a rec-type repair test with Proteus mirabilis strains PG713 (rec- hcr-) and PG273 (wild-type) and point mutations in the his- strain TA100 of Salmonella typhimurium: O,O-dimethyl-O-(1,2-dibromo-2,2-dichloroethyl)-phosphate (NALED); trichlorfon-O-methyl ether (TCP-O-ME), O,O-dimethyl-(1-methoxy-2,2,2-trichlorethyl)-phosphonate; trichlorfon-O-methyl ether vinyl derivative (TCP-O-MEVD), O,O-dimethyl-(1-methoxy-2,2-dichlorovinyl)-phosphonate. All compounds were negative in the repair test but induced base pair substitutions in S. typhimurium. The mutagenicity of NALED is due to the direct alkylating ability of the parental molecule and to mutagenic metabolites generated by enzymatic splitting of the side chain. Glutathion-dependent enzymes in the S9-mix eliminate the mutagenic activity of NALED completely. Mutation induction by TCP-O-ME and TCP-O-MEVD is predominantly caused by the reactive O-methyl ether configuration of the side chain and is resistant to metabolic inactivation by NADPH- or glutathion-dependent enzymatic pathways in the S9-mix of mice.

Studies of the persorption of large particles from radio-labelled cation exchangers.

Experiments were carried out in pigs to ascertain to what extent the cation exchangers Ujolyt and Campanyl used in the prevention of urinary stones undergo persorption and appear in the urine. We used two preparations of different grain size and detected them by labelling with 35S. A maximum of 0.5% or 5 X 10(-3) of the dose was found as persorbed particles at 51 h, chiefly in the muscles. The number of persorbed particles from the fine-grained preparation was considerably greater than that from the coarse-grained product. The urine contained the smallest proportion of particles, less than 2 X 10(-5) of the dose. In view of these results there is no reason to believe that solid particles persorbed during treatment with ion exchange resins can act as crystallization centres for stone formation, and it is equally unlikely that ion exchangers have to reach the urine before they can exert their effect.

Activity of organophosphorus insecticides in bacterial tests for mutagenicity and DNA repair--direct alkylation vs. metabolic activation and breakdown. I. Butonate, vinylbutonate, trichlorfon, dichlorvos, demethyl dichlorvos and demethyl vinylbutonate.

The following organophosphates were tested for their ability to induce DNA damage in a rec-type repair test with Proteus mirabilis strains PG713 (rec- hcr-) and PG273 (wild type) and point mutations in his- strain TA100 of Salmonella typhimurium--butonate: O,O-dimethyl-(1-n-butyryloxy-2,2,2-trichloroethyl)-phosphonate; vinylbutonate: O,O-dimethyl-(n-butyryloxy-2,2-dichlorovinyl)-phosphonate; trichlorfon: O,O-dimethyl-(1-hydroxy-2,2,2-trichloroethyl)-phosphonate; dichlorvos: O,O-dimethyl-O-(2,2-dichlorovinyl)-phosphate; the demethylated derivatives--demethyldichlorvos: O-methyl-O-(2,2-dichlorovinyl)-phosphoric acid; demethyl vinylbutonate: O-methyl-(1-n-butyryloxy-2,2-dichlorovinyl)phosphonic acid. Of the six compounds tested, dichlorvos and trichlorfon induced base pair substitutions and DNA damage. No mutagenicity and DNA damage were found in experiments with butonate, vinylbutonate, demethyl vinylbutonate and demethyl dichlorvos. Genotoxic activity for dichlorvos and the absence of both mutagenic and RNA damaging properties for its non-alkylating demethyl derivative favors the hypothesis that alkylation of DNA is the essential step for mutation induction by this organophosphate. Furthermore, the absence of genetic effects after treatment with vinylbutonate and demethyl dichlorvos does not support a crucial role of vinyl or allyl groups in side chains of organophosphates for genetic activity. Microsomal enzymes decreased genetic activity of dichlorvos and trichlorfon in vitro. No evidence for a role of metabolic activation in the mutagenic activity of any of these compounds was found.

[Disintegration and elimination of 32P-naled in milk]. / Abbau und Ausscheidung von 32P-Naled in der Milch.

The organophosphorus insecticide naled (O,O-dimethyl-O,O-(1,2-dibromo-2,2-dichloroethyl)-phosphate, labeled by 32P] is degraded in milk in vitro at 5 degrees C with a half-life of 35 h with dichlorvos as a metabolite, that is also formed at short time heating and UV-irradiation. The recovery in milk powder is 25% (naled + dichlorvos) of the initial concentration. Following spray application of 0,05 mg naled/kg body mass to 2 lactating cows, 5-8 ppb of naled and 7-9 ppb of dichlorvos were found in the milk 5 h p.a., not exceeding the given tolerance level of 0,02 mg/kg in the German Democratic Republic.

Guanine N7-alkylation in mice in vivo by metrifonate - discussion of possible genotoxic risk in mammals.

Following intraperitoneal administration to male mice (strain AB Jena/Halle) of 14CH3-labelled metrifonate, 22 Ci/mol, in dosages of 0.48, 0.40 and 0.065 mmol/kg, DNA from liver and kidneys was analysed for 14C in N-7 methylguanine (7-MeG). The extent of methylation in liver was found to be maximal at 6 hrs after injection in amounts of 6-8 and 0.8 mumol 7-MeG/mol guanine for the high and the low dose, corresponding to a covalent binding index CBI 4-5. The half-life of excretion of 7-MeG was 5 hrs for the high and 15 hrs for the low dose. The extent of methylation at 0-6 of guanine was estimated to be around 0.002-0.01 mumol 0-6 MeG/mol guanine. Data from references concerning methyl methanesulfonate and dimethyl sulfate are compared with those of metrifonate and the genotoxic response of methylating and non-methylating metabolites is discussed.

[Metabolism of 32P-butonate and formation of vinylbutonate metabolite in warm-blooded animals]. / Zum Metabolismus von 32P-Butonat und zur Bildung des Metaboliten Vinylbutonat im Warmblüter.

The metabolic fate of butonate, a 32P-labelled organophosphorus insecticide (0.0-dimethyl-l-n-butyryloxy-2.2.2-trichloro-ethyl phosphonate) was investigated in blood serum of cattle in vitro and in mice in vivo, following intraperitoneal and oral administration of 200 mg/kg. Metabolites were separates by thin-layer chromatography, using two solvent systems, acetonitrile-water = 85:15 and ethyl ether, for polar or non-polar metabolites. The Rf-values as well as the partition coefficients for chloroform and water and ethyl ether to ten per cent H2SO4 and for n-hexane and acetonitrile are given for butonate and the metabolites together with the amounts of metabolite, following in vivo metabolic degradation. The blood level as well as residues in milk are given by the following graduation: trichlorphone greater than vinylbutonate greater than butonate greater than dichlorvos. The formation of the new metabolite vinylbutonate is discussed.

[Metabolism and excretion of 32P-aminophon in lactating cattle]. / Metabolismus und Ausscheidung von 32P-Aminophon am laktierenden Rind.

P-labelled aminophon, 0,0-di-u-butyl- (1-n-butylaminocyclohexyl) -phosphonate, an agricultural defoliant and siccant, was applied orally in oily solution to lactating cows, 5-6 mg/kg bodymass, resp. The halflifes of degradation in blood serum in vitro are 95 min, of the extractable metabolites in blood, milk and urine 17-20 h. The 0-and 0, N-dealkylcompound of aminophon were found as the preferred metabolites.

[Metabolism, residue and excretion of the anthelmintic 131 I-rafoxanide in blood, milk, meat and urine of lactating cows]. / Metabolismus, Rückstände und Ausscheidung des Anthelminithikums 131J-Rafoxanid in Blut, Milch, Fleisch und Urin am laktierenden Rind.

Rafoxanide, labelled by 131J, was applied orally in the formulation "Ursovermit" to 2 lactating cows, 5 mg/kg bodymass, resp. Residues and halflifes in blood, milk and meat and the excretion in urine are given, related to 131J in the chloroform extract. 3,5-diiodosalicyclic acid was found as metabolite in amounts of 1-2,5%, relative to rafoxanide, resp.

[Residue determinations in milk following application of the fasciolicides rafoxanide and hexachloro-p-xylene]. / Rückstandsuntersuchungen bei Milch nach Anwendung der Fasziolizide Rafoxanid und Hexachlor-p-xylol.

The control of Fasciola hepatica in dairy cattle may lead to considerable residue problems in dairying. In the GDR, a hexachloro-p-xylene-based fasciolicide has been approved till recently, and another, rafoxanide-based fasciolicide has been on trial. The investigations have shown that the two active principles are excreted in the milk for a prolonged period, rafoxamide being found more suitable. Their marked lipophil behaviour leads to accumulation in the fat phase and, thus, in high-fat milk products.

[Behavior of selected veterinary preparations during industrial milk processing]. / Uber das Verhalten ausgewählter Tierarzneimittel bei der technologischen Verarbeitung der Milch

Since the extensive veterinary-hygienic treatment of herds with insecticidal veterinary preparations may lead to milk contamination, the authors studied the behaviour of some active agents (butonate, dichlorvos (DDVP), trichlorphon, naled, carbaryl, hexachloro-p-xylene and rafoxanide) during the industrial processing of milk to fluid milk, cream, butter, cheese and milk powder, and during the storage of these products. Small-scale model experiments served to investigate the effects of pasteurization (74 and 95 degrees C.), separation and churning as well as of the processing to milk powder and cheese. Analyses for residues were performed by thin-layer chromatography, colorimetry and with the aid of the isotope technique. From the viewpoint of milk processing, the use of TCP and, in part, that of DDVP may be considered as less critical due to their hydrophilic properties and rapid degradation. In view of their lipophilic behaviour, the use of butonate, carbaryl, rafoxanide and hexachloro-p-xylene as active agents in veterinary preparations for milk cows must be regarded as problematic. The utilization of naled is also problematic due to the fact that the toxicology of its metabolites is not yet sufficiently known.

[Degradation and residue dynamics of the anthelminthic 131J-rafoxanide in cattle blood, milk, meat and fat after various dosages]. / Abbau und Rückstandsdynamik des Anthelminthikums 131J-Rafoxanid in Blut, Milch, Fleisch und Fett bei unterschiedlicher Dosierung am Rind.

Rafoxanide, labelled by 131J, was applied orally in oily solution to cattle, 2,4 and 12 mg/kg bodymass, resp. The halflifes of degradation in blood is depending on the dosage and is 7 days related to the therapeutical dosage of 5 mg/kg bodymass against Fasciola hepatica. Residues and halflifer in blood, milk, meat and fat are given, related to 131J in the chloroform extract. Rafoxanide does not show persistence following oral application to cattle.