Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed.
Key details were compiled in summary tables. Approximate systemic Al exposure, a measure
of bioavailability, was calculated for each exposure, based on the Al percentage in
the dosed Al species, Al bioavailability, and absorption time course reports for the
exposure route. This was limited to laboratory animal studies because no controlled-exposure
human studies were found. Intended Al exposure was compared to unintended dietary
Al exposure. The considerable and variable Al content of laboratory animal diets creates
uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive
toxicity in female mice and rats was evident after exposure to >= 25-fold the amount
of Al consumed in the diet. Generally, the additional daily Al systemic exposure of
studies that reported statistically significant results was greater than 100-fold
above the typical human daily Al dietary consumption equivalent. Male reproductive
endpoints were significantly affected after exposure to lower levels of Al than females.
Increased Al intake increased fetus, placenta, and testes Al concentrations, to a
greater extent in the placenta than fetus, and, in some cases, more in the testes
than placenta. An adverse outcome pathway (AOP) was constructed for males based on
the results of the reviewed studies. The proposed AOP includes oxidative stress as
the molecular initiating event and increased malondialdehyde, DNA and spermatozoal
damage, and decreased blood testosterone and sperm count as subsequent key events.
Recommendations for the design of future studies of reproductive outcomes following
exposure to Al are provided.