Prenatal Developmental Toxicity Study in the Han Wistar Rat/MnCl2/OECD 414/Inhalation/GLP
The purpose of this study was to detect effects on the pregnant rat, development of the embryo and fetus consequent to exposure of the pregnant female via inhalation route (by nose-only, flow-past exposure) for risk assessment purposes and for gathering data necessary for modeling work safety scenarios.
A recovery group of non-mated females in all dose groups and the control group were observed for reversibility, persistence or delayed occurrence of systemic toxic effects in the lung- information necessary for establishing workplace task rotation strategies.
Four groups of 22 mated females (main study animals) and 6 non-mated females (recovery animals) were treated with manganese dichloride once daily, for 6 hours per day. Mated females were treated from day 6 post coitum (implantation) to day 20 post coitum (the day prior to Caesarean section) and recovery animals from day 1 to 15 of a concurrent treatment period at target dose levels of:
Group 1: 0 µg/L air (control group)
Group 2: 5 µg/L air
Group 3: 15 µg/L air
Group 4: 25 µg/L air
All mated females were sacrificed on day 21 post coitum and the fetuses were removed by Caesarean section. For the recovery animals, three females per group were sacrificed after four weeks and three females per group were sacrificed after eight weeks of the recovery period.
Based on these results, the NOAEL (No Observed Adverse Effect Level) as well as the NOEL (No Observed Effect Level) for the toxicity in pregnant females were considered to be 5 µg/L air.
In non-pregnant females, the NOEL for systemic toxicity was established at 15 µg/L air, whereas the NOAEL was established at 25 µg/L air.
Although the fetal thyroids increased in size were found at the dose level of 25 µg/L air, which caused adverse maternal toxicity, the causal correlation for these observations was unclear. Also, the outcome of the fetal finding for the postnatal live could not be conclusively established based on the results of this study. Therefore, the NOEL as well as NOAEL for prenatal developmental toxicity was considered to be 15 µg/L air.