Reaction mass of Benzene sulfonic acid, hexadecyl(sulfophenoxy)-,disodium salt and Benzene sulfonic acid, - oxibis[hexadecyl]-, disodium salt

Endpoint summary

Description of key information

To assess the ADME characteristics of DOWFAX™ 8390, QSAR predictions and data from the structurally similar linear alkylbenzene sulfonates (LAS) surfactants were utilized. The pharmacokinetic parameters for LAS from in vivo studies and QSAR predictions indicate substantial oral absorption. QSAR predictions for oral DOWFAX™ 8390 absorption in humans indicated lower absorption compared to LAS.  Dermal absorption of DOWFAX™ 8390 and LAS would be negligible, based on QSAR predictions and in vivo LAS data.  The ionic nature of the DOWFAX™ 8390 molecules indicates potential interactions with human plasma proteins upon absorption and hence low penetration into human tissues.  Based on the metabolism data of LAS, DOWFAX™ 8390 would be expected to be mainly metabolized to 4-[2-sulfo-3-(2-sulfophenoxy)phenyl]pentanoic acid and 3-[2-sulfo-3-(2-sulfophenoxy)phenyl] butanoic acid or their isomers and conjugated with sulfates or glucuronides.  Metabolites would be more water-soluble than the parent and would be expected to excrete in urine and feces. DOWFAX™ 8390 is not expected to be bioaccumulative. 
QSAR predictions for oral absorption of the two DOWFAX™ 8390 isomers indicate significantly lower absorption in human (< 0.001%).  

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

5

Absorption rate - inhalation (%):

100

Additional information

To assess the ADME characteristics of DOWFAX™ 8390, QSAR predictions and data from the structurally similar linear alkylbenzene sulfonates (LAS) surfactants were utilized.

The pharmacokinetic parameters for LAS from in vivo studies and QSAR predictions indicate substantial oral absorption. QSAR predictions for oral DOWFAX™ 8390 absorption in humans indicated lower absorption compared to LAS, with predicted values of 0.001% vs. 5%, respectively. Predicted permeability rates of two assessed DOWFAX™ 8390 structural isomers were 0.010 x 10^-4and 0.04 x 10^-4cm/s through jejunum. The corresponding absorption half-lives (t_1/2) are about 192 and 48 hours. The Caco-2 cell permeabilities were estimated to be 0.0 x 10^-6 cm/s for both DOWFAX^TM8390 isomers. The Log Kow values predicted with EPISUITE 4.1 for DOWFAX™ 8390 isomers were 4.4 and 5.2, wheras for LAS it was 3. Combined with higher MW of DOWFAX™ 8390, the lower oral absorption in humans in predicted compared to LAS.

Dermal absorption of DOWFAX™ 8390 and LAS would be negligible, based on QSAR predictions and in vivo LAS data.

The ionic nature of the DOWFAX™ 8390 indicates potential interactions with human plasma proteins (>99%) upon absorption. The volume of tissue distribution in humans is estimated to be low (0.4 L/kg). Consistent with high plasma protein binding affinity and low volume of tissue distribution, DOWFAX™ 8390 is estimated to have very low penetration into human tissues.

Based on the structural similarity between LAS and DOWFAX^TM 8390, the main metabolites would be expected to be 4-[2-sulfo-3-(2-sulfophenoxy)phenyl]pentanoic acid and 3-[2-sulfo-3-(2-sulfophenoxy)phenyl] butanoic acid or their isomers. These metabolites were predicted to be formed by degradation via ω-oxidation, followed by catabolism through a ß-oxidation mechanism. These metabolites would be conjugated with sulfates or glucuronides. Metabolites would be more water-soluble than the parent and would be expected to excrete in urine and feces.

DOWFAX™ 8390 is not expected to bioaccumulate.