Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

The registered substance is rapidly absorbed via skin and the gastrointestinal tract and widely distributed within the body. OPP is completely metabolised and predominantly excreted via the urine and, to a minor degree, via faeces. There was a low bioaccumulation potential noted in rodents, however, human data indicate that there is no bioaccumulation potential.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
43

Additional information

Data are available, investigating percutaneous absorption, metabolism and excretion of 14C/13C-2-phenylphenol (14C/13C-OPP) in male volunteers (Bartels, M. J. et al., 1997; Selim, S., 1996 and Bomhard, E. M. et al., 2002). The absorption, distribution, excretion and metabolism of [14C]-OPP was further investigated in young adult male B6C3F1 mice after oral intake. In addition the extent of metabolism was investigated in male and female Fischer 344 rats after oral intake (McNett et al., 1997 and Bomhard, E. M. et al., 2002).

Following 8 h of exposure OPP is rapidly absorbed via human skin with an absorption rate of approximately 43% (Selim, S., 1996 and Bomhard, E. M. et al., 2002). The vast majority of absorbed material is excreted within the first 24 h after application via the renal pathway. The entire absorbed dose is recovered in excreta, thus leaving no potential for systemic or dermal accumulation (Bartels, M. J. et al., 1997; Selim, S., 1996 and Bomhard, E. M. et al., 2002). The major metabolite identified in all urine samples analysed was the sulphate conjugate of OPP. This metabolite accounted for 68.33% of the absorbed dose. Conjugation of OPP with glucuronic acid was less significant, accounting for only 3.46% of the absorbed dose. Hydroxylation of the phenol or phenyl ring, followed by conjugation was shown to be significant, with the glucuronide conjugate of phenyl-hydroquinone (PHQ-Gluc) and 2, 4´ dihydroxy biphenyl-sulfate (2, 4´-DHB-Sulf) representing 14.34% and 12.35% of the absorbed dose, respectively. No sulphate conjugates of PHQ was observed in any of the urine samples analysed, contrary to metabolism of OPP in rat and mouse, in which comparable amounts of both PHQ-conjugates are found, independent from the applied dose. Low levels of free OPP (0.5% of absorbed dose) and the glucuronide conjugate (OPP-Gluc) were observed in the early time intervals. Free OPP was not observed in any of the analysed samples.

In tests with rats and mice after oral dosing (McNett et al., 1997 and Bomhard, E. M. et al., 2002), 97 and 105% of the administered OP (radiolabeld) were recovered after 24 and 48 h, respectively, indicating a fast and complete absorption of OPP via the gastrointestinal tract. Thus, OPP is rapidly bioavailable after oral dosing. Following oral uptake, OPP was shown to be completely metabolised and rapidly eliminated via the renal pathway, predominantly as a sulphate and glucuronide conjugate of OPP. Qualitatively the extent of metabolism was comparable between mice and rats, although quantitative differences in the extent of OPP sulfation and glucuronidation were seen between these species. Only 1% of the administered radioactivity was found in the tissues and carcass of rats, suggesting a low potential for bioaccumulation.

In summary, OPP is rapidly absorbed via skin and the gastrointestinal tract and widely distributed within the body. The bioavailability after oral intake is very high. OPP is completely metabolised and predominantly excreted via the urine and, to a minor degree, via faeces. There was a low bioaccumulation potential noted in rodents, however, human data indicate that there is no bioaccumulation potential.