Tissue distribution of styrene, styrene glycol and more polar styrene metabolites in the mouse.

Abstract

LOF A, GULLSTRAND E, BYFALT NORDQVIST M. Tissue distribution of styrene, styrene glycol and more polar styrene metabolites in the mouse. Scand j work environ health 9 (1983) 419-430. A primary objective of the present investigation was to detennine the tissue distribution of styrene, styrene glycol, and more polar metabolites in mice at different times (0.5-5 h) after the intraperitoneal administration of styrene (3.3 mmoll kg). Another aim was to determine the dose dependence of the metabolite pattern of styrene in the different tissues. The dose range chosen was 1.1-4.9 mmol of styrenelkg administered intraperitoneally, and the time delay 2 h after dosing. The highest initial concentrations of unchanged styrene were found in adipose tissue, pancreas, liver, and brain. Styrene glycol reached its maximum concentration within 1 h in most tissues. The levels in the kidneys, lungs, pancreas, and liver far exceeded those in subcutaneous adipose tissue. Only in the liver and kidneys was a notable amount of styrene glycol conjugated. Polar metabolites occurred to a considerable extent in the liver, kidneys, lungs, and plasma. The concentration of unmetabolized styrene seemed to increase exponentially with the dose in subcutaneous adipose tissue, liver, kidneys, lungs, and brain. No tendency towards a decreased relative occurrence of styrene glycol was observed at higher doses. However, when the dose was increased, the more polar metabolites occurred at relatively lower levels in all tissues except brain.

Occurrence of styrene-7,8-oxide and styrene glycol in mouse after the administration of styrene.

“…The accumulation of total radioactivity after the intraperitoneal administration of 7-[I4C]-styrene agreed well with the results of our earlier study (16). The concentrations of styrene are given in figure 2.…”

“…Styrene and its metabolites were rapidly distributed in the tissues as has earlier been discussed in detail (16). A possible explanation of the linear dose-response curve for styrene in the pancreas (figure 3) may be related to the route of administration, whereas the deviation from linearity seen for the other tissues may reflect a diminished metabolism at higher doses.…”

“…Recently we reported the occurrence of styrene-7,8-oxide in human blood ( 3 9 , and in the blood and other tissues of mice (17). After the initial findings of conjugated styrene glycol in rat urine (12, 21) styrene glycol has been determined as an in vivo metabolite of styrene in mouse tissues (16) and in blood from experimentally exposed volunteers and occupationally exposed workers (35,36). The main purpose of the present study was to detect styrene-7,8-oxide and, if possible, quantify this epoxide and its importance in the metabolism of styrene.…”

“…Human exposure to styrene mainly occurs via inhalation (34), and absorbed styrene is, according to animal studies, rapidly distributed in the body (4, 37). A predominant part is distributed in a metabolized form (16).…”

Detection of Styrene and Styrene Oxide‐Induced DNA Damage in Various Organs of Mice Using the Comet Assay

“…The degree of accumulation of the substances in the various organs could also explain this phenomenon. Tissue distribution studies (Lof et al 1983) have shown that mice intraperitoneal administered styrene accumulate the major level of the substance in fat, followed by the pancreas, liver and kidney. Although styrene is suspected to induce leukaemia among workers engaged in styrene industry there is no report of leukaemia from experimental animal studies.…”