Distribution of benzo[a]pyrene in pregnant rats following inhalation exposure and a comparison with similar data obtained with pyrene

Abstract

Eight pregnant rats were exposed, on the 17th day of gestation, for 95 min to a microcondensation aerosol of benzo[a]pyrene at five different atmospheric concentrations between 200 and 800 mg m-3 in a 'head-only' inhalation chamber. Five rats were killed immediately following the exposure and three were killed at 6 h post-dosing. Concentrations of the radiolabel and 'free' benzo[a]pyrene were measured in the individual fetuses and in the maternal blood, fat, kidney, liver and lung. Distribution to the fetus did not appear to be related to its position on the uterine horn and the uptake of benzo[a]pyrene was non-linear with increasing exposure concentrations, which was similar to the observations previously reported for pyrene. The levels of benzo[a]pyrene were much higher in the fetus and, especially, the lung than those observed in the pyrene study; so also were the levels of total metabolites in these tissues, which might, in part, account for the carcinogenic potency of benzo[a] pyrene.

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

“…This effect is more pronounced for slowly perfused tissues. A typical example of such a tissue is adiposal fat which, despite a very high tissue/blood partition coefficient, contains low concentrations of PAHs shortly after exposure but has the highest relative concentrations longer after exposures (Withey et al, 1993a). For physiologically based pharmacokinetic models to predict better the systemic distribution of PAHs and their metabolites, the delayed equilibration between blood and tissue needs to be taken into account.…”

“…14 C]-labelled benzo [a]pyrene aerosol for 95 min on gestation day 17, radiolabel was detected, as the parent compound and metabolites, in maternal blood samples collected immediately after exposure (Withey et al, 1993a). The detection of high levels of radioactivity in the lung and liver of these rats is consistent with the occurrence of mucociliary clearance from the respiratory tract and ingestion into the oesophagus and gastrointestinal tract, as well as rapid absorption, metabolism and biliary excretion of metabolites (Withey et al, 1994).…”

“…Results from studies in rats indicate that: (i) absorbed PAHs are widely distributed to most organs and tissues; (ii) fatty tissues can serve as storage sites to which PAHs may be gradually absorbed and from which they are then released; and (iii) the gastrointestinal tract can contain high levels of PAHs and their metabolites following exposure (by any route) due to mucociliary clearance from the respiratory tract and hepatobiliary excretion of metabolites (Mitchell & Tu, 1979;Mitchell, 1982Mitchell, , 1983Sun et al, 1984;Withey et al, 1991Withey et al, ,1993a. For example, immediately after a 95-min inhalation exposure of pregnant rats to [ 3 H]-labelled benzo [a]pyrene aerosols, levels of radiolabel associated with parent compound in the tissues decreased in the following order: lung > blood > liver > kidney > fat > fetus; 6 h after cessation of exposure, the order was fat > lung > kidney > liver > blood > fetus (Withey et al, 1993a).…”

“…For example, immediately after a 95-min inhalation exposure of pregnant rats to [ 3 H]-labelled benzo [a]pyrene aerosols, levels of radiolabel associated with parent compound in the tissues decreased in the following order: lung > blood > liver > kidney > fat > fetus; 6 h after cessation of exposure, the order was fat > lung > kidney > liver > blood > fetus (Withey et al, 1993a). Similarly, about 7 h after a 95-min inhalation exposure of male rats to [ , levels of radiolabel associated with parent compound decreased in the following order: fat > kidney > lung > liver > testes > spleen > brain (Withey et al, 1994).…”

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“…O trato gastrointestinal contém quantidades relativamente altas de metabólitos de HPAs como resultado da excreção hepatobiliar (Scheled et al 1970). Alguns HPAs, como no caso do benzo(a)pireno, podem cruzar rapidamente a barreira placentária de ratos e camundongos (Neubert & Tapken 1988, Withey et al 1993) concordando com os dados sobre toxicidade para o feto e seu desenvolvimento.…”