Plasma superwarfarin levels and vitamin K1 treatment in dogs with anticoagulant rodenticide poisoning.

The plasma concentration, plasma half-life (t1/2), and mean residence time (MRT) of rodenticide anticoagulants were determined in 21 dogs in which a preliminary diagnosis of anticoagulant rodenticide poisoning had been made. Brodifacoum, difethialone, and difenacoum were detected by high-performance liquid chromatography (HPLC) in the plasma of 13, 3, and 2 dogs, respectively. At presentation the plasma concentration ranged from below the detection limit (10 ng/L) to 851 ng/L. Toxin could not be detected in 3 dogs, despite these animals showing characteristic coagulation disturbances and a positive response to therapy with vitamin K1. In 7 dogs the estimated t1/2 of brodifacoum ranged from 0.9 to 4.7 (median 2.4) days with a MRT of 1.9 to 3.7 (median 2.8) days. In 2 dogs the individual t1/2 of difethialone was 2.2 and 3.2 days and the MRT was 2.3 and 2.8 days, respectively. Two dogs died during emergency treatment. Treatment in the remaining 19 dogs consisted of the administration of vitamin K1 and supportive therapy. The dose of vitamin K1 was reduced in a stepwise manner as long as the prothrombin time remained within physiological limits. The variation in initial plasma concentrations of the anticoagulants combined with the results of treatment support the idea that an individual therapeutic approach is warranted.

[Anticoagulant rodenticide poisoning in dogs in The Netherlands]. / Rodenticide anticoagulans-intoxicatie bij honden in Nederland.

The occurrence, the diagnosis, and the treatment of anticoagulant rodenticide poisoning in dogs in the Netherlands was evaluated by a survey among Dutch veterinarians carried out by the National Poisons Control Center (NPCC). The survey included information on 54 dogs, 32 being treated by veterinarians who consulted the NPCC and 22 that were admitted to the Utrecht University Clinic for Companion Animals (UUCCA). The poisons that were suspected were brodifacoum (n = 19), bromadiolone (n = 14), difenacoum (n = 8), difethialone (n = 6) and chlorophacinone (n = 1). In 6 dogs the identity of the poison was unknown. Of 31 dogs with hemorrhages, 2 died shortly after presentation to practitioners and 2 died shortly after admission to the UUCCA. Signs of bleeding occurred especially in poisoning by brodifacoum (n = 16). In all but one of the dogs without hemorrhages, the intake of poison had taken place within 24 hours before presentation. The method of treatment varied, with the induction of vomiting and the use of vitamin K mentioned most. The choice of therapy was determined by the length of time after intake of the poison, the clinical signs and whether or not an anticoagulant toxicosis was suspected at the time of the initial examination. These findings provide the basis for discussion of several aspects of diagnosis and treatment.

Inhalation exposure in Drosophila mutagenesis assays: experiments with aliphatic halogenated hydrocarbons, with emphasis on the genetic activity profile of 1,2-dichloroethane.

A series of mutation experiments was carried out with Drosophila melanogaster using inhalation exposure. 1,2-Dichloroethane (DCE) and 1,2-dibromoethane (DBE) were active in the sex-linked recessive lethal assay (SLRLT), whereas dichloromethane, dibromomethane, 1,2-dichloropropane and 1,3-dichloropropane were not. Compared to DBE, DCE is a less potent mutagen in the SLRL system. For both compounds, there is no evidence of a clear-cut dose-rate effect. DCE and dichloromethane were also investigated in the somatic mutation and recombination test (SMART), with results similar to those from the SLRLT. For DCE the genetic activity profile was further analyzed by carrying out a sex-chromosome loss assay and a complementation analysis of a series of induced recessive lethal mutations. A review of the use of inhalation in mutagenicity assays with Drosophila shows that this route of exposure is an effective one. Especially with chronic exposure times, rather low exposure concentrations can be detected. With compounds of intermediate volatility inhalation is not superior to other modes of administration; nor is it likely to be sensitive enough for in situ monitoring.

Mutagenic activity of acrylamide in eukaryotic systems but not in bacteria.

The vinyl monomer acrylamide (AA) was studied for its activity in a range of genotoxicity tests, including the Salmonella/microsome test, the fluctuation test using Klebsiella pneumoniae, the test for gene mutations at the TK and HPRT loci in L5178Y mouse lymphoma cells, tests for chromosomal aberrations and SCEs in V79 Chinese hamster cells, the sex-linked recessive lethal (SLRL) and somatic mutation and recombination (SMART) assays in Drosophila melanogaster and the mouse bone marrow micronucleus assay. AA showed genotoxic activity in most systems. The bacterial tests did not respond, in compliance with literature data; also in the Drosophila SLRL test, no significant increase in mutation rate was observed.