**6. Reproductive system**

It is well known that boron has negative effects on male and female reproductive system. It causes atrophy in seminifer tubulus, germ cell loss, sperm mobility impairment, altered follicle stimulating hormone and testosterone, reduction of ovulation processes [4]. Exposure to a range of boric acid concentrations between 1000 and 9000 ppm causes serious male fertility problems such as testicular atrophy and decreased sperm motility in experimental animals. With the studies on different species of animals, these toxic effects were confirmed with different doses. Human studies with occupational workers in Turkey and in China did not confirm these results [29, 30]. As a result of a study conducted in Russia, it was determined that sexual activity decreased in boron workers (n = 28). In addition, interestingly, in the study conducted on boron workers in the United States, it was determined that there was an increase in the birth of girls compared with boys [7].

According to animal studies, it was reported that boron, boric acid, and sodium borate compounds could be toxic to reproductive system and also developmental system. For reproductive system, NOAEL levels of boron were 17.5 mg /kg/day and for developmental issue NOAEL levels of boron were 9.6 mg/kg/day. Duydu et al. reported that daily 14.45 ± 6.57 mg/day boron exposure in boron workers did not lead to any change in reproduction-related hormone levels (FSH, LH) and sperm cells morphology and count [31].

In different studies, it was shown that low levels of boron compounds caused developmental problems. Low levels disrupted developmental processes of chicken (400 mg B/L drinking water), rat (640 mg B/L drinking water), and African ostrich (640 mg boric acid/L) experimentally. In another study, boric acid exposure higher than 0.5 mmol/L in male rats' Sertoli cells triggered necrosis and apoptosis and caused a decrease in cell viability rate. At 40 and 80 mmol/L boric acid levels, it was reported that sertoli cell viability was arrested at G0/G1 phase [32].

In one lineage study, male rats were exposed to boron via oral gavage with different concentrations. Then they mated with unexposed female rats. It was observed that fetus viability rate decreased at higher exposure levels (100 mg B/kg/day) and fetus malformations increased at higher concentration. Additionally, testicular enzyme levels (MDH, SDH, G3PDH) and FSH levels changed. These changes were associated with lipid metabolism changes that play a key role in hormone and enzyme activities via metabolomic assays [33].
