Relative Subnarcotic Potency of Solvents Predicted by Partition Co-efficients
Emil Frantík, Ludmila Vodièková, Miroslava Hornychová,
Michal Nosek
Centre of Industrial Hygiene and Occupational Diseases, National Institute
of Public Health, Praha, Czech Republic
Corresponding author: E. Frantík
National Institute of Public Health,
robárova 48, 100 42 Praha 10, Czech Republic,
Tel.: (+42) 2 67082628
Fax: (+42) 2 67311236
CEJOEM 1998, Vol.4. No.1.:25-35
Key words:
Chlorinated aliphatic solvents, chemical hazard, CNS effects
Abbreviations:
Ca air concentration
Cb blood concentration
EC effective concentration
ECa iso-effective air concentration at EC30
ECb iso-effective blood concentration
EC30 concentration in air evoking 30% of the maximum possible value
of biological response
PCba partition co-efficient blood/air
PCfa partition co-efficient fat/air
PCfb partition co-efficient fat/blood
PCoa partition co-efficient octanol-air
PCob partition co-efficient octanol-blood
PCow partition co-efficient octanol-water
PCwa partition co-efficient water/air
PCwb partition co-efficient water/blood
PCs partition co-efficients
Abstract:
Airborne concentrations of nine chlorinated aliphatic solvents necessary
to produce the same degree of inhibition of seizure discharge generation
and maintenance (by 30%, ECa) were determined in rats after a single 4-hour
inhalatory exposure. The corresponding blood concentrations of solvents
(ECb) were measured using gas chromatography. Partition co-efficients blood/air,
fat/air and water/air were determined experimentally; partition co-efficients
fat/blood (PCfb) and water/blood (PCwb) were calculated.
The equipotent air concentrations ranged from 2.2
to 6.9 mg · l1 (403 to 1980 ppm), the corresponding blood levels
from 0.08 to 0.8 mmol · 11. The internal relative potency (measured
as reciprocal of iso-effective blood levels, 1/ECb) and less successfully
the external relative potency (reciprocal of iso-effective air concentrations,
1/ECa) were effectively represented by the fat/blood partition co-efficient
or by a linear combination of fat/blood and water/blood PCs. The derived
formula predicted also historical data on aromatic hydrocarbons. The regression
equations based on joint data (9 chlorinated hydrocarbons, 5 aromatics
and acetone) predicted iso-effective blood levels but not iso-effective
air concentrations of additional 6 chlorinated hydrocarbons. PCfb could
be replaced by PCoctanol/blood (PCow x PCwb) but not by PCow in most predictive
equations without substantial loss of efficiency.
The results can be interpreted in terms of constant
target structure concentration and substance specific target structure/blood
partition co-efficients for the acute subnarcotic effect of solvents (and
anaesthetics), and support thus the feasibility of predicting such effects
from partition co-efficients and blood level data.
Received: 20 October, 1997
Accepted: 5 February, 1998
| Back
|
Posted: 15 November 1998