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Description of key information

Short description of key information on bioaccumulation potential result: 
A GLP-study on metabolism of PPh in rats after oral administration is available for phenoxypropanol

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential

Additional information

Based on the results of a study in male rats, PPh is rapidly absorbed, distributed, and quickly metabolized and eliminated. Virtually all the administered dose is eliminated within 48 hours in the urine and feces. The three major routes of metabolism are 1) cleavage of PPh by O-dealkylation, yielding propylene glycol and phenol, followed by excretion of phenol as a sulfate, or glutathione conjugate in the urine; 2) direct sulfate or glucuronide conjugation of parent PPh and excretion into the urine; and 3) ring hydroxylation of parent PPh or its oxidized propanone metabolite, followed by sulfate conjugation and excretion into the urine. Minor urinary metabolites included the glucuronide conjugate of hydroquinone. PPh is rapidly absorbed, distributed throughout the body, and eliminated, similar to other propylene glycol ethers (PGEs). The major routes of elimination, urine and feces, also are similar to other PGEs. The types of metabolites, parent ether conjugates, hydrolyzed propylene glycol, and hydrolyzed alcohol (phenol) conjugates, also are similar.

Discussion on bioaccumulation potential result:

Adult, male F344 rats were administered a single oral dose of 10 or 100 mg/kg radiolabeled DOWANOL PPh. The major route of elimination of DOWANOL PPh was through urine, accounting for 88 ± 12% of the low and 96 ± 3% of the high dose. Most of the urinary excretion of DOWANOL PPh derived radioactivity occurred within 12 hr after dosing; 81 ± 9% of the low and 90 ± 1% of the high dose. Total fecal elimination remained < 10% during the course of the study. Rats eliminated the entire administered dose within 48 hr after dosing, with total recovery ranging from 100 – 106%. Metabolites tentatively identified in urine were conjugates of phenol (sulfate, glutathione), as well as conjugates of parent compound (glucuronide, sulfate) and a ring-hydroxylated metabolite of parent. There was no free parent compound or phenol detected in non-acid-hydrolyzed urine. In acidhydrolyzed urine, 61% of the dose was identified as phenol and 13% as DOWANOL PPh. Although the parent compound was stable to acid hydrolysis, some of the phenol in acid hydrolyzed urine may have come from degradation of acid-labile metabolite(s) as well as hydrolysis of phenol conjugates.

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