A study on formation of hemoglobin adduct due to inhalation exposure with 1,3-butadiene in female mice

The purpose of this study is the identification of (N-2-hydroxy-3-butenyl) valine(HBVal adduct) and (N-2,3,4-trihydroxy-butyl)valine(THBVal adduct)with mice inhalation exposure with 1,3-butadiene for 3 weeks($6\;hr/day\;{\times}\;5\;days/week$). Body weights were significantly lower from 4 or 9 exposure post-day in 1000 or 500ppm inhalation group than in control. The levels of HBVal adducts are 1.8, 3.7 and 6.2 pmol/mg globin in $1^{st}$, $2^{nd}$ , and $3^{rd}$ week for 500 ppm 1,3-butadiene(BD), and 5.7, 7.4 and 16.0 pmol/mg globin in $1^{st}$, $2^{nd}$ , and $3^{rd}$ week for 1000 ppm BD inhalation exposure. The levels of THBVal adducts are 32.0, 42.0 and 55.0 pmol/mg globin in $1^{st}$, $2^{nd}$ , and $3^{rd}$ week for 500 ppm BD, and 67.8, 72.7 and 83.5 pmol/mg globin in $1^{st}$, $2^{nd}$ , and $3^{rd}$ week for 1000 ppm BD inhalation exposure. Their ratios of THBVal and HBVal adducts are higher at earlier exposure and lower concentration. They are17.8, 11.4 and 8.87 in $1^{st}$, $2^{nd}$ , and $3^{rd}$ week for 500 ppm BD, and 11.9, 9.8 and 5.2 in $1^{st}$, $2^{nd}$ , and $3^{rd}$ week for 1000 ppm BD inhalation exposure. In conclusion, THBVal and HBVal adducts are a important hemoglobin adduct for monitoring of BD exposure, and the latter is more biomarker than the other.