Reaction mass of (3E)-1,1,1,2,2,3,4,5,6,6,7,7,7-tridecafluoro-5-methoxyhept-3-ene and (2E)-1,1,1,2,3,4,5,5,6,6,7,7,7-tridecafluoro-4-methoxyhept-2-ene and (3E)-1,1,1,2,2,4,5,5,6,6,7,7,7-tridecafluoro-3-methoxyhept-3-ene

Endpoint summary

Additional information

Absorption toxicokinetics study of the test substance in SD rats was performed to obtain toxicokinetic information by different doses and routes of administration. Three parts were contained in this study, including a toxicokinetics study by acute intravenous administration (single dose to tail vein at 10 mg/kg), a toxicokinetics study by acute oral administration (1500 and 30000 mg/kg) and a toxicokinetics study by repeated dose 14-day oral administration (1500 mg/kg). Blood was withdrawn (by direct venous puncture) from the jugular vein at 0.5, 2, 4, 6, 8, l0, 12, 14, 16, 20, 24, and 36 hours after the last oral administration and at 1, 5, 15, 30 minutes, and 1, 2, 4, 6, 10, and 24 hours after the intravenous administration. The concentration of the test substance was determined by gas chromatography-mass spectrometry (GC/MS) method. Parameters of C_max (maximal concentration in blood after administration), AUC (area under the plasma concentration-time curve), half-life (t_1/2), T_max (time to reach C_max), V_z (volume of distribution) and bioavailability were compared among different groups.

Seven peaks (A through G) of isomers were detected by GC/MS. The ratio of peak areas of these seven isomers to the total peak area was constant. The summation of peaks A, C and E was more than 85% of the total peak area. Few samples of the other four peaks were higher than the limit of quantitation, which was not suitable for analysis. The measured toxicokinetics characteristics of peaks A, C, and E of the substance are indicated below:

Single intravenous injection (10 mg/kg):

A: AUC(0-t) 66.48 ± 9.91 µg/L*h, Cmax 335.72 ± 68.73 µg/L, Vz 7.68 ± 3.54 L/kg, T1/2z 0.31 ± 0.13 h.

C: AUC(0-t) 337.32 ± 51.53 µg/L*h, Cmax 1492.25 ± 297.84 µg/L, Vz 8.62 ± 3.84 L/kg, T1/2z 0.36 ± 0.12 h.

E: AUC(0-t) 90.72 ± 16.58 µg/L*h, Cmax 471.27 ± 88.04 µg/L, Vz 7.33 ± 1.38 L/kg, T1/2z 0.25 ± 0.07 h.

Single oral administration (1500 mg/kg):

A: AUC(0-t) 210.85 ± 44.40 µg/L*h, Cmax 23.17 ± 5.42 µg/L, Tmax 4.67 ± 1.63 h, T1/2z 20.40 ± 15.59 h, bioavailability 2.11%.

C: AUC(0-t) 1121.56 ± 187.12 µg/L*h, Cmax 106.40 ± 22.40 µg/L, Tmax 5.67 ± 0.82 h, T1/2z 13.09 ± 7.79 h, bioavailability 2.22%.

E: AUC(0-t) 308.50 ± 68.94 µg/L*h, Cmax 31.19 ± 6.62 µg/L, Tmax 5.67 ± 0.82 h, T1/2z 17.53 ± 23.91 h, bioavailability 2.27%.

Single oral administration (30000 mg/kg):

A: AUC(0-t) 2129.26 ± 325.82 µg/L*h, Cmax 517.50 ± 59.93 µg/l, Tmax 2.00 ± 0 h, T1/2z 12.54 ± 4.87 h, bioavailability 1.07%.

C: AUC(0-t) 10226.39 ± 1163.75 µg/L*h, 1:9, Cmax 2331.20 ± 222.82 µg/L, 1:21.9, Tmax 2.00 ± 0 h, T1/2z 11.39 ± 2.65 h, bioavailability 1.01%.

E: AUC(0-t) 3527.55 ± 488.99 µg/L*h, 1:11.4, Cmax 814.97 ± 69.92 µg/L, 1:26.1, Tmax 2.00 ± 0 h, T1/2z 13.81 ± 3.98 h, bioavailability 1.30%.

Repeated dose 14-day oral administration (1500 mg/kg)

A: AUC(0-t) 183.02 ± 39.90 µg/L *h,

C: AUC(0-t) 1631.73 ± 302.66 µg/L *h

E: AUC(0-t) 308.21 ± 51.83 µg/L*h

Activities of rats slightly reduced immediately after single oral exposure to the test substance (30000 mg/kg). No abnormal symptoms of rats treated with the test substance (30000 mg/kg) were found after one hour of treatment. No abnormal symptoms of rats in other groups were found during the test period. When comparing the AUC values of the single versus repeated dose oral studies at the same dose level (1500 mg/kg), the P values (T-test) were 0.28, 0.0056 and 0.99 for peaks A, C and E, respectively. The change in AUC for peak C was significant but the increase was small. This result indicated that the test substance may have limited cumulative effects in rats after repeated exposure.