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Administrative data

Link to relevant study record(s)

Description of key information

Experimental ADME data are not available for DOWFAX 2A1 surfactant. QSAR programs were used to assess the ADME potential of two major alkylated components of DOWFAX 2A1 in humans.

Based on the systemic bioavailability predictions for DOWFAX 2A1, both oral and dermal bioavailability were conservatively set to 50%, whereas systemic inhalation bioavailability was set to 100%. DOWFAX 2A1 metabolites would be mainly excreted via urine and feces.

On the basis of low volume of distribution, and predicted metabolism and excretion, DOWFAX 2A1 is not expected to bioaccumulate in humans.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
50
Absorption rate - inhalation (%):
100

Additional information

See attached for full discussion of toxicokinetic potential and ADME report of DOWFAX 2A1.

 

Experimental data on absorption, distribution, metabolism and excretion (ADME) are not available for DOWFAX 2A1 surfactant.  To assess the ADME potential of the major monoalky and dialkyl diphenyl ether sulfates components of DOWFAX 2A1 in humans, QSAR programs, ADMET predictor (v7.2, Simulations Plus Inc, Lancaster, CA, USA) and GastroPlus (v9.0, Simulations Plus Inc, Lancaster, CA, USA) were used.  

 

Based on the 90-day repeated exposure scenario at the dose level of 9 mg/kg/day, the predicted oral fractional absorption (Fa%), CYP based metabolism related bioavailability (%), AUC0-2160 (area under curve, µg h/mL) value for the most abundant monoalkyl diphenyl ether sulfate DOWFAX 2A1 component in humans by GastroPlus were 25.7%, 14.9%, and 30800, respectively.  In the same exposure scenario, the predicted oral fractional absorption (Fa%), CYP based metabolism related bioavailability (%), AUC0-2160 (area under curve, µg h/mL) value for the dialkyl diphenyl ether sulfate component in humans by GastroPlus were 94.8%, 55.0%, and 11800, respectively.

 

Based on 90-day repeated exposure scenario at the dose level of 90 mg/kg/day, the predicted dermal fractional absorption (Fa%), CYP based metabolism related bioavailability (%), AUC0-2160 (area under curve, µg h/mL) value for the monoalkyl diphenyl ether sulfate component in humans by GastroPlus were 0.16%, 0.00%, and 0.00%, respectively.  In the same exposure scenario, the predicted dermal fractional absorption (Fa%), CYP based metabolism related bioavailability (%), AUC0-2160 (area under curve, µg h/mL) value for the dialkyl diphenyl ether sulfate component in humans by GastroPlus were 0.00277%, 0.00%, and 0.00%, respectively. Thus, DOWFAX 2A1 is not predicted to be systemically bioavailable in humans via dermal exposure route.

 

Based on the systemic bioavailability predictions for DOWFAX 2A1, both oral and dermal bioavailability were conservatively set to 50%, whereas systemic inhalation bioavailability was adjusted to 100% for DNEL derivation.   

 

The major predicted CYP-dependent DOWFAX 2A1 metabolites were various monohydroxylates on the alkyl side chains and can be further metabolized to water soluble metabolites (such as glucuronides and sulfates). DOWFAX 2A1 metabolites would be mainly excreted via urine and feces.

 

On the basis of low volume of distribution, and predicted metabolism and excretion, DOWFAX 2A1 is not expected to bioaccumulate in humans.