Interaction of chlorpromazine, fluphenazine and trifluoperazine with ocular and synthetic melanin in vitro.

The aim of this study was to examine in vitro the binding capacity of three phenothiazine derivatives--chlorpromazine, fluphenazine and trifluoperazine--causing adverse effects in the eye structures, to natural melanin isolated from pig eyes as well as to synthetic DOPA-melanin used as a model polymer. The amount of drug bound to melanin was determined by UV spectrophotometry. The analysis of results for the kinetics of drug-melanin complex formation showed that the amount of drug bound to melanin increases with increasing initial drug concentration and longer incubation time, attaining an equilibrium state after about 24 h. Binding parameters, i.e. the number of binding sites (n) and association constants (K), were determined on the basis of Scatchard plots. For neuroleptic-ocular melanin and neuroleptic-DOPA-melanin complexes two classes of independent binding sites were found, with association constants K1 approximately 10(4) and K2 approximately 10(2) M (-1) for chlorpromazine and fluphenazine complexes, and K1 approximately 10(5) and K2 approximately 10(3) M(-1) for trifluoperazine complexes. The numbers of strong (n1) and weak (n2) binding sites indicate lower affinity of the drugs examined to ocular melanin compared with DOPA-melanin. The ability of chlorpromazine, fluphenazine and trifluoperazine to interact with melanin, especially the ocular melanin, in vitro is discussed in relation to the ocular toxicity of these drugs in vivo.

Interaction of quinidine, disopyramide and metoprolol with melanin in vitro in relation to drug-induced ocular toxicity.

The aim of this work was to evaluate binding capacity of quinidine, disopyramide and metoprolol to melanin in vitro. The antiarrhythmics studied cause adverse reactions to the eye. Synthetic DOPA-melanin was used in the studies and a UV spectrophotometric method was employed to determine the drugs. The studies of the kinetics of the formation of quinidine-melanin, disopyramide-melanin and metoprolol-melanin complexes indicate that for all the complexes investigated the maximum time to reach reaction equilibrium is 24 h. Binding parameters, i.e., the numbers of independent binding sites and the association constants were determined on the basis of the Scatchard plots. An analysis of the binding curves obtained supports our conclusion that both strong (n1) and weak (n2) binding sites are involved in the formation of the complexes investigated. The total numbers of binding sites in synthetic DOPA-melanin complexes with quinidine, disopyramide and metoprolol were 0.525, 0.493 and 0.387 micromol/mg, respectively. The quinidine-melanin complex is characterized by greater stability (K1 = 3.00 x 10(5) M(-1), K2 = 1.75 x 10(3) M(-1)) in comparison with biopolymer complexes with disopyramide (K1 = 1.12 x 10(4) M(-1), K2 = 6.04 x 10(2) M(-1)) and metoprolol (K1 = 1.42 x 10(4) M(-1), K2 = 7.89 x 10(2) M(-1)). The ability of these drugs to form complexes with melanin in vitro may be one of the reasons for their ocular toxicity in vivo, as a result of their accumulation in melanin in the eye.

A mathematical model for the estimation of nickel internal dose in populations under occupational and environmental exposure.

Using the results of own investigations as well as available literature data an attempt was made to develop a mathematical model for the estimation of nickel internal dose on the basis of nickel concentration in urine.

Identification and evaluation of nickel intake sources.

The level of nickel in a full-day diet, drinking water and complementary liquids was measured in groups of persons occupationally and environmentally exposed to this element. Both adults and children (in preschool and school age) living in industrial and recreation areas were considered. Concentrations of nickel in the occupational and ambient air were also taken into account. Measurement data were used for calculating the intake and uptake of nickel in the investigated groups. It was found that contaminated air at workplaces under occupational exposure, and food under environmental exposure were the main sources of the nickel intake.

Occupational and environmental exposure to nickel in Poland.

Exposure to nickel was evaluated on the base of nickel in urine concentration (Ni-U) in 649 persons both adults and pre-school and school children; 241 persons were occupationally exposed in steel-mill and rolling-mill. Environmentally exposed groups consisted of inhabitants of industrial and rural towns. The occupationally exposed groups showed Ni-U mean concentrations amounted to 25.7, 18.1, 15.9, and 15.7 micrograms/m3. In environmentally exposed groups of adults, Ni-U concentrations were almost equal to those in persons inhabiting industrial and rural areas-7.8 and 7.7.micrograms/dm3, respectively. Ni-U concentrations in children groups were more differentiated 8.5 and 9.2 micrograms/dm3 in rural area and 9.9 and 10.6 micrograms/dm3 in industrial area. The recommended mean group allowable Ni-U concentrations for occupational exposure amounts to 12 micrograms/dm3 and for environmental exposure 2.7 micrograms/dm3. In view of the above mentioned Ni-U allowable values it is evident that there exist significant occupational exposure and elevated environmental exposure in the defined percent of the investigated population.

[Levels of metabolites of selected chemical compounds in the urine of workers in pitch coke plant]. / Poziom metabolitów wybranych zwiazków chemicznych w moczu pracowników koksowni pakowej.

In urine samples collected from pitch coke plant workers just before and after occupational exposure, differentiated concentrations of phenol (20.8-692.8 mg/dm3), p-cresol (51.8-590 mg/dm3), I-naphtol (4.9-63.7 mg/dm3) and benzo(a)pyrene (0.3-18.9 ug/dm3) have been found. The occurrence of enhanced concentrations of phenol in 10.1%, p-cresol in 31.9%, I-naphthol in 13.5% and benzo(a)pyrene in 72.8% of the test urine specimens collected prior to exposure points to a slow excretion of these metabolites of chemical compounds inherent in the work environment. Furthermore, the urinary level of the metabolites in particular coke plant workers points to different individual exposure.

[Choice of the conditions for collecting urine samples for assessing occupational exposure of electric steel plant workers to nickel, chromium, manganese and copper]. / Dobór warunków pobierania próbek moczu dla oceny ekspozycji zawodowej pracowników elektrostalowni na nikiel, chrom, mangan i miedz.

The concentrations of Ni, Cr, Mn and Cu were determined in single urine samples of Electric Steel Works Workers, collected three times during a workshift on the 1st and fourth working days. The obtained results permitted settlement of optimum duration of urine samples collection, i.e. the fourth day after at least four hours. Basing on the determined concentrations of Ni, Cr, Mn and Cu the magnitude of Electric Steel Works workers' exposure was evaluated.