Aluminum reproductive toxicity: a summary and interpretation of scientific reports

Abstract

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.

The Effect of Aluminum Exposure on Maternal Health and Fetal Growth in Rats

“…Accordingly, Lin et al [16] observed a dose-dependent relationship between Alu intake and intrauterine growth retardation in mice and suggested that excessive Alu ingestion during pregnancy may be one of the risk factors contributing to congenital neural tube defects and perinatal deaths. Also, in agreement with our findings, many previous studies that used different doses of Alu have shown that Alu was both embryotoxic and fetotoxic, resulting in growth retardation, increased mortality, increased resorptions, multiple congenital malformations, a variety of adverse reproductive outcomes, and alteration in neuromotor maturation in exposed animals [1,2,10,17].…”

“…During the early period of pregnancy, women may use large amounts of Alu-containing antacids as they may have gastric symptoms that may result in increased Alu intake, which in turn considerably increases Alu plasma levels in pregnant females [ 9 ]. It was reported that Alu can pass through the placenta to fetuses [ 10 ].…”

Interactions between Environmental Factors and Glutathione S-Transferase (GST) Genes with Respect to Detectable Blood Aluminum Concentrations in Jamaican Children

“…Even though Al is not required for any biological process in humans and animals, it can be a metallic toxicant at high concentrations after natural or unnatural exposure [ 4 , 5 ]. Exposure to Al has been linked to several adverse health effects, such as asthma [ 6 , 7 ], bone disease [ 8 , 9 , 10 ], immunotoxicity [ 11 , 12 ], congenital malformations [ 13 ], and reproductive toxicity in laboratory animals [ 14 , 15 ]. For example, children with early life exposure to a high level of Al had lower lumbar spine bone mass and lower hip bone mass [ 10 ].…”

Peer review of the pesticide risk assessment of the active substance aluminium ammonium sulfate

“…With regard to adverse effects on spermatogenesis and testes, it was noted that rat is a poor model for effect on spermatogenesis and male fertility; therefore, potential effects (as reported in previous reviews) might not have been detected in these last two studies. In the review by Yokel ( 2020 ), adverse effects on spermatogenesis and testes have also been indicated. However, the experts agreed that there is no concern for a potential reproductive effect following exposure to aluminium ammonium sulfate applied as plant protection product (PPP) because it is not expected to contribute significantly to the general exposure to aluminium via other sources (e.g.…”