PESTICIDES: MECHANISM OF ACTION AND DISTRIBUTION IN THE BIOSPHERE
Main researcher
: REINER, ELSA (40695) Assistants
DREVENKAR, VLASTA (10591)
FINGLER, SANJA (14292)
FROBE, ZLATKO (59066)
KRAUTHACKER, BLANKA (23413)
RADIĆ, ZORAN (100102)
ROZGAJ, RUICA (100135)
SIMEON, VERA (43160)
KRINJARIĆ-POLJAR, MIRA (47456)
VASILIĆ, ELIMIRA (51642)
KOVARIK, ZRINKA (900812)
HERCEG, SNJEANA (900881)
Type of research: basic Duration from: 01/01/91. to 12/31/94. Papers on project (total): 165
Papers on project quoted in Current Contents: 42
Institution name: Institut za medicinska istraivanja i medicinu rada, Zagreb (22) Department/Institute: Laboratory of Biochemistry Laboratory of Organic Analytical Chemistry Address: Ksaverska cesta 2 City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0) 1 434188
Phone: 385 (0) 1 273132
Fax: 385 (0) 1 274572
E-mail: VERA.SIMEON@X400.IRB.HR
E-mail: ZLATKO.FROBE@X400.IRB.HR
Summary: The project has five parts. The mechanism of interaction of
human serum cholinesterase and its genetic variants, as well as of
the native and mutant acetylcholinesterase of T. californica was
studied with substrates and inhibitors. Phenotyping of serum
cholinesterases was done for a group of healthy individuals from
Zagreb, and the reproducibility of phenotyping evaluated. The
specificity of phosphoric triester hydrolases was studied in human sera
from healthy individuals, from individuals with lipid and/or glucose
metabolism disorders, and from elderly demented patients. The number of
enzymes hydrolysing paraoxon, beta-naphthylacetate and phenylacetate
was evaluated, and their calcium requirement established. The kinetics
of excretion of organophosphorus compounds was studied in accidentally
poisoned individuals by measuring levels of the parent compound and
its metabolites in urine and blood. Metabolites in the urine proved
to be a more sensitive indicator of absorption than blood
cholinesterase inhibition. The mechanism of delayed neurotoxicity of
organophosphorus compounds was studied in experimental animals
(hen, rat). Monitoring of organochlorine pesticides and
polychlorinated biphenyls (PCB) in human milk and serum, and
chlorophenols in human urine, was conducted in population groups
from Croatia. Levels were similar to those reported for
west-European countries. The origin and levels of organochlorine and
triazinic pesticides, PCB and chlorophenols were studied in aqueous
media (surface, ground and drinking water, snow and rainwater); some
physico-chemical parameters were investigated which affect their
distribution between the solid and aqueous phase. The biodegradation
of PCB with mixed bacterial cultures isolated from the river Sava
was studied. Scientists from the project organized the "Second
International Meeting on Esterases Hydrolysing Organophosphorus
Compounds" in 1992; the papers in extenso were published in a
special issue of Chemico-Biological Interactions. During the present
war the scientists from the project worked out a field test for
detecting organophosphorus compounds in drinking water; the test
reagents were assembled by "Pliva". The field-kit has been succesfully
used by the Croatian Army and Croatian health service authorities. For
the Croatian Army, samples of soil, water and oil from vehicles were
tested for contamination with pesticides and PCB. The efficiency of
charcoal to remove pesticides from drinking water was tested in
collaboration with the Croatian Army Sanitary Headquarter. The
described results were published in 46 papers in scientific journals
(42 in journals cited in CC), 24 papers in proceedings and books, 9
reports and 53 communications; furthermore, the project theme was
comprised in 2 books, 13 invited lectures and 8 theses.
Keywords: Pesticides, Organophosphorus compounds, Organochlorine compounds, Polychlorinated biphenyls, PCB, Triazinic compounds, Biochemistry, Analytical chemistry, Toxicology, Monitoring of pesticides in water and wet depositions, Monitoring of pesticides in human milk, serum and urine, Serum cholinesterase phenotypes, Human serum phosphoric triester hydrolases, Blood cholinesterases, Inhibition of esterases with organophosphorus compounds, Inhibition of esterases with EDTA, Classification of esterases, Pharmacokinetics of organophosphorus compounds in humans, Sorption behaviour of pesticides in soil and sediments, Biodegradation of PCB by mixed bacterial cultures.
Research goals: The project has five parts. In part one, the aim was
to obtain information on the frequency of serum cholinesterase phenotypes
in population groups from Croatia and to evaluate the catalytic properties
of phenotypes with respect to the enzyme primarystructure. In part two,
the aim was to evaluate the specificity of phosphoric triester hydrolases
with respect to organophosphorus compounds and some carboxylic acid
esters, and to evaluate the enzyme activities as possible markers of
glucose and/or lipid metabolism disorders. In part three, the aim was to
evaluate biological markers for human absorption of organophosphorus
compounds (cholinesterase inhibition, levels of metabolites) and to
investigate the pharmacokinetics of these compounds in accidentally
exposed individuals. In part four, the aim was to measure levels of
organochlorine pesticides and PCB in human milk and serum, to evaluate the
intake of these compounds by breast-fed infants, and to measure
chlorophenols in human urine as further indicators of exposure to
organochlorine compounds. In part five, the aim was to investigate levels
and origins of organochlorine and triazinic pesticides, chlorophenols and
PCB in aqueos media, and to evaluate factors which affect partition of
those compounds between aqueos and solid phase. The elimination of
persistent organochlorine pollutants from water by biodegradation was also
investigated.
COOPERATION - PROJECTS
Name of project
: 3-01-185: KRONOBIOLOGIJA STARAČKE DEMENCIJE Name of institution: Zavod za psihijatrijska istraivanja kliničke
psihijatrijske bolnice Vrapče City: 10000 - Zagreb, Croatia
Name of project
: 3-01-131: OCJENA UKUPNE IZLOENOSTI LJUDI
ONEČIĆENJIMA U OKOLINI Name of institution: Institut za medicinska istraivanja i medicinu
rada City: 10000 - Zagreb, Croatia
Name of project
: 3G0A6A: ESTERASES AND ORGANOPHOSPHORUS
COMPOUNDS Name of institution: Institut fr Biochemie und Molekulare
Zellbiologie Georg-August Universitt Gttingen i Friedrich Ebert
Krankenhaus Neumnster City: Gttingen i Neumnster, Njemačka
Name of project
: ALIS 1995: CATALYTIC PROPERTIES OF HUMAN SERUM
CHOLINESTERASE VARIANTS Name of institution: St. James's University Hospital, Department of
Chemical Pathology City: LS9 7TF - Leeds, Engleska
Name of project
: JF250 i JF251: MONITORING OF ORGANOCHLORINE
COMPOUNDS IN CONIFEROUS TREES AND AMBIENT AIR, AND IN HUMAN MILK Name of institution: US Environmental Protection Agency (EPA) City: NC 27711 - Research Triangle Park,NC, SAD
Name of project
: RZ Alpe-Jadran MONITORING OF ORGANOCHLORINE
COMPOUNDS IN THE BIOSPHERE Name of institution: Intitut za varovanje zdravja Rep. Slovenije,
Centro internazionale per la sicurezza degli antiparassitary i Pannon
agricultural university - Faculty of animal science City: Ljubljana,Milano,Kaposvar, Slovenija,Italija,Mađarsk
Name of project
: WHO-Copenhagen: LEVELS OF PCBs, PCDDs AND PCDFs
IN BREAST MILK Name of institution: WHO - Regional Office for Europe City: Copenhagen, Danska
Name of project
: COST 66: FATE OF PESTICIDES IN THE SOIL AND THE
ENVIRONMENT Name of institution: European Commission, Directorate-General XII,
Science, Research and Developement City: Bruxelles, Belgija
COOPERATION - INSTITUTIONS
Name of institution
: "ZGO" javno poduzeće za gospodarenje
otpadom i zatitu okolia Type of institution: Other Type of cooperation: Systematic exchange of information City: 10000 - Zagreb, Croatia
Name of institution
: Bundesinstitut fr gesundheitlichen
Verbraucherschutz und Veterinrmedizin Type of institution: State institute Type of cooperation: Joint project City: Berlin, Njemačka
Name of institution
: Department of Pharmacology, University of
California San Diego Type of institution: University/Faculty Type of cooperation: Occasional exchange of experts City: San Diego-La Jolla, SAD
Name of institution
: Eidgenssische Anstalt fr
Wasserversorgung, Abwasserreinigung und Gewsserschutz (EAWAG) Type of institution: State institute Type of cooperation: Systematic exchange of information City: Dbendorf, vicarska
Name of institution
: Istituto di Medicina del Lavoro Universita
di Padova Type of institution: University/Faculty Type of cooperation: Occasional exchange of experts City: Padova, Italija
Name of institution
: Medicinski centar Sisak Type of institution: Institution whose primary activities ar Type of cooperation: Occasional exchange of information City: 44000 - Sisak, Croatia
Name of institution
: Medicinski fakultet Sveučilita u Zagrebu Type of institution: University/Faculty Type of cooperation: Occasional exchange of information City: 10000 - Zagreb, Croatia
Name of institution
: Norsk Institutt for Luftforskning Type of institution: State institute Type of cooperation: Systematic exchange of information City: Lillestrom, Norveka
Name of institution
: Prirodoslovno-matematički fakultet
Sveučilita u Zagrebu Type of institution: University/Faculty Type of cooperation: Joint publishing of scientific papers City: 10000 - Zagreb, Croatia
Name of institution
: Rijksinstituut voor Volksgesondheit en
Milieuhygiene Type of institution: State institute Type of cooperation: Joint project City: Bilthoven, Nizozemska
Name of institution
: Agronomski fakultet Sveučilita u Zagrebu Type of institution: University/Faculty Type of cooperation: Joint publishing of scientific papers City: 10000 - Zagreb, Croatia
Name of institution
: Stanica za hitnu medicinsku pomoć Type of institution: Institution whose primary activities ar Type of cooperation: Joint publishing of scientific papers City: 10000 - Zagreb, Croatia
Name of institution
: Toxicology Unit Medical Research Council Type of institution: State institute Type of cooperation: Joint publishing of scientific papers City: Carlshalton, Velika Britanija Other information about the project.