An inhalation exposure assessment of Hexafluoroisobutylene in pregnant rats

Hexafluoroisobutylene (HFIB) is an important compound widely used in semiconductor lithography materials, refrigerants, fluorine coatings, and pharmaceutical intermediates in the fluorination industry. Owing to its toxicity, the occupational exposure in the workplace, especially for pregnant woman is the concern and there is still lack of the data of HFIB toxicity on pregnancy and fetal development. Here, for the first time, we investigated the effects of HFIB on pregnant rats and fetal development. The pregnant rats were exposed to different doses of HFIB (0 ppm, 27.2 ppm, 53.5 ppm, 105.6 ppm) via whole-body inhalation for the period of organogenesis, which from implantation (gestation day 5) to the day prior to scheduled caesarean section (gestation day 19). The results showed that the pregnant rats exposed to 105.6 ppm HFIB displayed systemic toxicity, including a decrease in body weight and food consumption, as well as tracheal inflammation, pulmonary interstitial inflammation and renal tubular swelling. Moreover, reduced fetal and placental weights, delayed ossification, and a reduced number of ossification centers were observed in fetuses delivered by pregnant rats exposed to 105.6 ppm. These effects were attributed to severe maternal weight loss. In addition, it would be useful to note that no whole-body, visceral or skeletal congenital malformations were observed. However, HFIB exposure at 53.5 ppm showed no significant adverse effects on pregnant rats and fetuses. These findings demonstrate that 105.6 ppm HFIB is a toxic concentration, while 53.5 ppm HFIB is the no-observed-adverse-effect concentration (NOAEC) for both pregnancy and fetal development. This study for the first time to provide evidence for the health risk of HFIB exposure on pregnancy and fetal development.