char = A;code = 65 char = ;code = 32 char = p;code = 112 char = h;code = 104 char = y;code = 121 char = s;code = 115 char = i;code = 105 char = o;code = 111 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = b;code = 98 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = o;code = 111 char = k;code = 107 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = (;code = 40 char = P;code = 80 char = B;code = 66 char = B;code = 66 char = K;code = 75 char = );code = 41 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = l;code = 108 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = o;code = 111 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = t;code = 116 char = o;code = 111 char = x;code = 120 char = i;code = 105 char = f;code = 102 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = .;code = 46 result sql = A physiologically based biokinetic (PBBK) model for estragole bioactivation and detoxification in rat.
A physiologically based biokinetic (PBBK) model for estragole bioactivation and detoxification in rat.char = T;code = 84 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = s;code = 115 char = t;code = 116 char = u;code = 117 char = d;code = 100 char = y;code = 121 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = f;code = 102 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = p;code = 112 char = h;code = 104 char = y;code = 121 char = s;code = 115 char = i;code = 105 char = o;code = 111 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = b;code = 98 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = o;code = 111 char = k;code = 107 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = t;code = 116 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = (;code = 40 char = P;code = 80 char = B;code = 66 char = B;code = 66 char = K;code = 75 char = );code = 41 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = l;code = 108 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = l;code = 108 char = k;code = 107 char = e;code = 101 char = n;code = 110 char = y;code = 121 char = l;code = 108 char = b;code = 98 char = e;code = 101 char = n;code = 110 char = z;code = 122 char = e;code = 101 char = n;code = 110 char = e;code = 101 char = ;code = 32 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = b;code = 98 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = v;code = 118 char = i;code = 105 char = t;code = 116 char = r;code = 114 char = o;code = 111 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = a;code = 97 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = s;code = 115 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = m;code = 109 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = u;code = 117 char = s;code = 115 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = l;code = 108 char = e;code = 101 char = v;code = 118 char = a;code = 97 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = i;code = 105 char = s;code = 115 char = s;code = 115 char = u;code = 117 char = e;code = 101 char = ;code = 32 char = f;code = 102 char = r;code = 114 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = s;code = 115 char = i;code = 105 char = l;code = 108 char = i;code = 105 char = c;code = 99 char = o;code = 111 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = t;code = 116 char = i;code = 105 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = e;code = 101 char = f;code = 102 char = f;code = 102 char = i;code = 105 char = c;code = 99 char = i;code = 105 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = p;code = 112 char = h;code = 104 char = y;code = 121 char = s;code = 115 char = i;code = 105 char = o;code = 111 char = l;code = 108 char = o;code = 111 char = g;code = 103 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = a;code = 97 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = s;code = 115 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = f;code = 102 char = r;code = 114 char = o;code = 111 char = m;code = 109 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = u;code = 117 char = r;code = 114 char = e;code = 101 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = l;code = 108 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = i;code = 105 char = s;code = 115 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = e;code = 101 char = i;code = 105 char = g;code = 103 char = h;code = 104 char = t;code = 116 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = t;code = 116 char = m;code = 109 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = l;code = 108 char = u;code = 117 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = l;code = 108 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = r;code = 114 char = ,;code = 44 char = ;code = 32 char = l;code = 108 char = u;code = 117 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = k;code = 107 char = i;code = 105 char = d;code = 100 char = n;code = 110 char = e;code = 101 char = y;code = 121 char = ;code = 32 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = z;code = 122 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = t;code = 116 char = m;code = 109 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = a;code = 97 char = d;code = 100 char = d;code = 100 char = i;code = 105 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = t;code = 116 char = m;code = 109 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = f;code = 102 char = a;code = 97 char = t;code = 116 char = ,;code = 44 char = ;code = 32 char = a;code = 97 char = r;code = 114 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = i;code = 105 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = b;code = 98 char = l;code = 108 char = o;code = 111 char = o;code = 111 char = d;code = 100 char = ,;code = 44 char = ;code = 32 char = v;code = 118 char = e;code = 101 char = n;code = 110 char = o;code = 111 char = u;code = 117 char = s;code = 115 char = ;code = 32 char = b;code = 98 char = l;code = 108 char = o;code = 111 char = o;code = 111 char = d;code = 100 char = ,;code = 44 char = ;code = 32 char = r;code = 114 char = a;code = 97 char = p;code = 112 char = i;code = 105 char = d;code = 100 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = p;code = 112 char = e;code = 101 char = r;code = 114 char = f;code = 102 char = u;code = 117 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = i;code = 105 char = s;code = 115 char = s;code = 115 char = u;code = 117 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = s;code = 115 char = l;code = 108 char = o;code = 111 char = w;code = 119 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = p;code = 112 char = e;code = 101 char = r;code = 114 char = f;code = 102 char = u;code = 117 char = s;code = 115 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = i;code = 105 char = s;code = 115 char = s;code = 115 char = u;code = 117 char = e;code = 101 char = .;code = 46 char = ;code = 32 char = E;code = 69 char = v;code = 118 char = a;code = 97 char = l;code = 108 char = u;code = 117 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = l;code = 108 char = ;code = 32 char = w;code = 119 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = p;code = 112 char = e;code = 101 char = r;code = 114 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = b;code = 98 char = y;code = 121 char = ;code = 32 char = c;code = 99 char = o;code = 111 char = m;code = 109 char = p;code = 112 char = a;code = 97 char = r;code = 114 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = P;code = 80 char = B;code = 66 char = B;code = 66 char = K;code = 75 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = e;code = 101 char = d;code = 100 char = i;code = 105 char = c;code = 99 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = -;code = 45 char = d;code = 100 char = e;code = 101 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = d;code = 100 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = 4;code = 52 char = -;code = 45 char = a;code = 97 char = l;code = 108 char = l;code = 108 char = y;code = 121 char = l;code = 108 char = p;code = 112 char = h;code = 104 char = e;code = 101 char = n;code = 110 char = o;code = 111 char = l;code = 108 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = 1;code = 49 char = ';code = 39 char = -;code = 45 char = h;code = 104 char = y;code = 121 char = d;code = 100 char = r;code = 114 char = o;code = 111 char = x;code = 120 char = y;code = 121 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = g;code = 103 char = l;code = 108 char = u;code = 117 char = c;code = 99 char = u;code = 117 char = r;code = 114 char = o;code = 111 char = n;code = 110 char = i;code = 105 char = d;code = 100 char = e;code = 101 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = u;code = 117 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = p;code = 112 char = o;code = 111 char = r;code = 114 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = l;code = 108 char = e;code = 101 char = v;code = 118 char = e;code = 101 char = l;code = 108 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = e;code = 101 char = s;code = 115 char = ,;code = 44 char = ;code = 32 char = w;code = 119 char = h;code = 104 char = i;code = 105 char = c;code = 99 char = h;code = 104 char = ;code = 32 char = w;code = 119 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = m;code = 109 char = o;code = 111 char = n;code = 110 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = s;code = 115 char = a;code = 97 char = m;code = 109 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = r;code = 114 char = d;code = 100 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = g;code = 103 char = n;code = 110 char = i;code = 105 char = t;code = 116 char = u;code = 117 char = d;code = 100 char = e;code = 101 char = .;code = 46 char = ;code = 32 char = W;code = 87 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = o;code = 111 char = d;code = 100 char = e;code = 101 char = l;code = 108 char = ;code = 32 char = o;code = 111 char = b;code = 98 char = t;code = 116 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = t;code = 116 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = o;code = 111 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = t;code = 116 char = o;code = 111 char = x;code = 120 char = i;code = 105 char = f;code = 102 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = d;code = 100 char = i;code = 105 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = o;code = 111 char = r;code = 114 char = a;code = 97 char = l;code = 108 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = w;code = 119 char = a;code = 97 char = s;code = 115 char = ;code = 32 char = e;code = 101 char = x;code = 120 char = a;code = 97 char = m;code = 109 char = i;code = 105 char = n;code = 110 char = e;code = 101 char = d;code = 100 char = .;code = 46 char = ;code = 32 char = A;code = 65 char = t;code = 116 char = ;code = 32 char = l;code = 108 char = o;code = 111 char = w;code = 119 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = s;code = 115 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = 4;code = 52 char = -;code = 45 char = a;code = 97 char = l;code = 108 char = l;code = 108 char = y;code = 121 char = l;code = 108 char = p;code = 112 char = h;code = 104 char = e;code = 101 char = n;code = 110 char = o;code = 111 char = l;code = 108 char = ,;code = 44 char = ;code = 32 char = l;code = 108 char = e;code = 101 char = a;code = 97 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = d;code = 100 char = e;code = 101 char = t;code = 116 char = o;code = 111 char = x;code = 120 char = i;code = 105 char = f;code = 102 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ,;code = 44 char = ;code = 32 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = b;code = 98 char = s;code = 115 char = e;code = 101 char = r;code = 114 char = v;code = 118 char = e;code = 101 char = d;code = 100 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = j;code = 106 char = o;code = 111 char = r;code = 114 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = t;code = 116 char = h;code = 104 char = w;code = 119 char = a;code = 97 char = y;code = 121 char = ,;code = 44 char = ;code = 32 char = o;code = 111 char = c;code = 99 char = c;code = 99 char = u;code = 117 char = r;code = 114 char = r;code = 114 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = l;code = 108 char = u;code = 117 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = k;code = 107 char = i;code = 105 char = d;code = 100 char = n;code = 110 char = e;code = 101 char = y;code = 121 char = ;code = 32 char = d;code = 100 char = u;code = 117 char = e;code = 101 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = w;code = 119 char = i;code = 105 char = t;code = 116 char = h;code = 104 char = ;code = 32 char = h;code = 104 char = i;code = 105 char = g;code = 103 char = h;code = 104 char = ;code = 32 char = a;code = 97 char = f;code = 102 char = f;code = 102 char = i;code = 105 char = n;code = 110 char = i;code = 105 char = t;code = 116 char = y;code = 121 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = r;code = 114 char = g;code = 103 char = a;code = 97 char = n;code = 110 char = s;code = 115 char = .;code = 46 char = ;code = 32 char = S;code = 83 char = a;code = 97 char = t;code = 116 char = u;code = 117 char = r;code = 114 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = t;code = 116 char = h;code = 104 char = w;code = 119 char = a;code = 97 char = y;code = 121 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = l;code = 108 char = u;code = 117 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = k;code = 107 char = i;code = 105 char = d;code = 100 char = n;code = 110 char = e;code = 101 char = y;code = 121 char = ;code = 32 char = l;code = 108 char = e;code = 101 char = a;code = 97 char = d;code = 100 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = p;code = 112 char = r;code = 114 char = o;code = 111 char = x;code = 120 char = i;code = 105 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = a;code = 97 char = r;code = 114 char = c;code = 99 char = i;code = 105 char = n;code = 110 char = o;code = 111 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = 1;code = 49 char = ';code = 39 char = -;code = 45 char = h;code = 104 char = y;code = 121 char = d;code = 100 char = r;code = 114 char = o;code = 111 char = x;code = 120 char = y;code = 121 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ,;code = 44 char = ;code = 32 char = o;code = 111 char = c;code = 99 char = c;code = 99 char = u;code = 117 char = r;code = 114 char = r;code = 114 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = i;code = 105 char = n;code = 110 char = l;code = 108 char = y;code = 121 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = l;code = 108 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = r;code = 114 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = i;code = 105 char = s;code = 115 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = 1;code = 49 char = ';code = 39 char = -;code = 45 char = h;code = 104 char = y;code = 121 char = d;code = 100 char = r;code = 114 char = o;code = 111 char = x;code = 120 char = y;code = 121 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = l;code = 108 char = e;code = 101 char = a;code = 97 char = d;code = 100 char = s;code = 115 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = f;code = 102 char = o;code = 111 char = r;code = 114 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = 1;code = 49 char = ';code = 39 char = -;code = 45 char = h;code = 104 char = y;code = 121 char = d;code = 100 char = r;code = 114 char = o;code = 111 char = x;code = 120 char = y;code = 121 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = g;code = 103 char = l;code = 108 char = u;code = 117 char = c;code = 99 char = u;code = 117 char = r;code = 114 char = o;code = 111 char = n;code = 110 char = i;code = 105 char = d;code = 100 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = n;code = 110 char = d;code = 100 char = ;code = 32 char = 1;code = 49 char = ';code = 39 char = -;code = 45 char = s;code = 115 char = u;code = 117 char = l;code = 108 char = f;code = 102 char = o;code = 111 char = o;code = 111 char = x;code = 120 char = y;code = 121 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = t;code = 116 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = b;code = 98 char = e;code = 101 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = u;code = 117 char = l;code = 108 char = t;code = 116 char = i;code = 105 char = m;code = 109 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = c;code = 99 char = a;code = 97 char = r;code = 114 char = c;code = 99 char = i;code = 105 char = n;code = 110 char = o;code = 111 char = g;code = 103 char = e;code = 101 char = n;code = 110 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = .;code = 46 char = ;code = 32 char = T;code = 84 char = h;code = 104 char = e;code = 101 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = s;code = 115 char = u;code = 117 char = l;code = 108 char = t;code = 116 char = s;code = 115 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = d;code = 100 char = i;code = 105 char = c;code = 99 char = a;code = 97 char = t;code = 116 char = e;code = 101 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = t;code = 116 char = h;code = 104 char = e;code = 101 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = m;code = 109 char = p;code = 112 char = o;code = 111 char = r;code = 114 char = t;code = 116 char = a;code = 97 char = n;code = 110 char = c;code = 99 char = e;code = 101 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = d;code = 100 char = i;code = 105 char = f;code = 102 char = f;code = 102 char = e;code = 101 char = r;code = 114 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = m;code = 109 char = e;code = 101 char = t;code = 116 char = a;code = 97 char = b;code = 98 char = o;code = 111 char = l;code = 108 char = i;code = 105 char = c;code = 99 char = ;code = 32 char = p;code = 112 char = a;code = 97 char = t;code = 116 char = h;code = 104 char = w;code = 119 char = a;code = 97 char = y;code = 121 char = s;code = 115 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = m;code = 109 char = a;code = 97 char = y;code = 121 char = ;code = 32 char = v;code = 118 char = a;code = 97 char = r;code = 114 char = y;code = 121 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = -;code = 45 char = d;code = 100 char = e;code = 101 char = p;code = 112 char = e;code = 101 char = n;code = 110 char = d;code = 100 char = e;code = 101 char = n;code = 110 char = t;code = 116 char = ;code = 32 char = w;code = 119 char = a;code = 97 char = y;code = 121 char = ,;code = 44 char = ;code = 32 char = l;code = 108 char = e;code = 101 char = a;code = 97 char = d;code = 100 char = i;code = 105 char = n;code = 110 char = g;code = 103 char = ;code = 32 char = t;code = 116 char = o;code = 111 char = ;code = 32 char = a;code = 97 char = ;code = 32 char = r;code = 114 char = e;code = 101 char = l;code = 108 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = c;code = 99 char = r;code = 114 char = e;code = 101 char = a;code = 97 char = s;code = 115 char = e;code = 101 char = ;code = 32 char = i;code = 105 char = n;code = 110 char = ;code = 32 char = b;code = 98 char = i;code = 105 char = o;code = 111 char = a;code = 97 char = c;code = 99 char = t;code = 116 char = i;code = 105 char = v;code = 118 char = i;code = 105 char = a;code = 97 char = t;code = 116 char = i;code = 105 char = o;code = 111 char = n;code = 110 char = ;code = 32 char = o;code = 111 char = f;code = 102 char = ;code = 32 char = e;code = 101 char = s;code = 115 char = t;code = 116 char = r;code = 114 char = a;code = 97 char = g;code = 103 char = o;code = 111 char = l;code = 108 char = e;code = 101 char = ;code = 32 char = a;code = 97 char = t;code = 116 char = ;code = 32 char = h;code = 104 char = i;code = 105 char = g;code = 103 char = h;code = 104 char = e;code = 101 char = r;code = 114 char = ;code = 32 char = d;code = 100 char = o;code = 111 char = s;code = 115 char = e;code = 101 char = s;code = 115 char = .;code = 46 char = <;code = 60 char = b;code = 98 char = r;code = 114 char = /;code = 47 char = >;code = 62 result sql = The present study defines a physiologically based biokinetic (PBBK) model for the alkenylbenzene estragole in rat based on in vitro metabolic parameters determined using relevant tissue fractions, in silico derived partition coefficients, and physiological parameters derived from the literature. The model consists of eight compartments including liver, lung and kidney as metabolizing compartments, and additional compartments for fat, arterial blood, venous blood, rapidly perfused tissue and slowly perfused tissue. Evaluation of the model was performed by comparing the PBBK predicted dose-dependent formation of the estragole metabolites 4-allylphenol and 1'-hydroxyestragole glucuronide to literature reported levels of these metabolites, which were demonstrated to be in the same order of magnitude. With the model obtained the relative extent of bioactivation and detoxification of estragole at different oral doses was examined. At low doses formation of 4-allylphenol, leading to detoxification, is observed to be the major metabolic pathway, occurring mainly in the lung and kidney due to formation of this metabolite with high affinity in these organs. Saturation of this metabolic pathway in the lung and kidney leads to a relative increase in formation of the proximate carcinogenic metabolite 1'-hydroxyestragole, occurring mainly in the liver. This relative increase in formation of 1'-hydroxyestragole leads to a relative increase in formation of 1'-hydroxyestragole glucuronide and 1'-sulfooxyestragole the latter being the ultimate carcinogenic metabolite of estragole. These results indicate that the relative importance of different metabolic pathways of estragole may vary in a dose-dependent way, leading to a relative increase in bioactiviation of estragole at higher doses.
Publication: Toxicol. Appl. Pharmacol. 2008 Sep 1 ;231(2)::248-59. :doi: 10.1016/j.taap.2008.04.011.
Publication Date: 2008 Sep 1
Study Author(s): Punt, Ans;Freidig, Andreas P;Delatour, Thierry;Scholz, Gabriele;Boersma, Marelle G;Schilter, Benoît;van Bladeren, Peter J;Rietjens, Ivonne M C M;
Institution: Division of Toxicology, Wageningen University, Tuinlaan 5, 6703HE Wageningen, The Netherlands.
[email protected]
Shortcut link to this study:
The present study defines a physiologically based biokinetic (PBBK) model for the alkenylbenzene estragole in rat based on in vitro metabolic parameters determined using relevant tissue fractions, in silico derived partition coefficients, and physiological parameters derived from the literature. The model consists of eight compartments including liver, lung and kidney as metabolizing compartments, and additional compartments for fat, arterial blood, venous blood, rapidly perfused tissue and slowly perfused tissue. Evaluation of the model was performed by comparing the PBBK predicted dose-dependent formation of the estragole metabolites 4-allylphenol and 1'-hydroxyestragole glucuronide to literature reported levels of these metabolites, which were demonstrated to be in the same order of magnitude. With the model obtained the relative extent of bioactivation and detoxification of estragole at different oral doses was examined. At low doses formation of 4-allylphenol, leading to detoxification, is observed to be the major metabolic pathway, occurring mainly in the lung and kidney due to formation of this metabolite with high affinity in these organs. Saturation of this metabolic pathway in the lung and kidney leads to a relative increase in formation of the proximate carcinogenic metabolite 1'-hydroxyestragole, occurring mainly in the liver. This relative increase in formation of 1'-hydroxyestragole leads to a relative increase in formation of 1'-hydroxyestragole glucuronide and 1'-sulfooxyestragole the latter being the ultimate carcinogenic metabolite of estragole. These results indicate that the relative importance of different metabolic pathways of estragole may vary in a dose-dependent way, leading to a relative increase in bioactiviation of estragole at higher doses.
PMID: 18539307