4-tert-butylphenol

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Dose-dependent shifts in the sulfation and glucoronidation of phenolic compounds in the rat in vivo and in isolated hepatocytes

Author:

Koster H, Halsema I, Scholtens E, Knippers M, Mulder GJ

Year:

1981

Bibliographic source:

Biochem Pharmacol; 30(18):2569-75

Reference 2

Reference Type:

publication

Title:

Ecotoxicological profile analysis

Author:

Freitag D, Geyer H, Kraus A, Viswanathan R, Kotzias D, Attar A, Klein W, Korte F.

Year:

1982

Bibliographic source:

Ecotoxicol Environmental Safety; 6:60-81

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

p-tert.-Butylphenol

IUPAC Name:

p-tert.-Butylphenol

Details on test material:

- Name of test material (as cited in study report): p-tert.-Butylphenol
- Substance type: pure active substance
- Physical state: solid
- Stability under test conditions: no data
- Storage condition of test material: under nitrogen in the dark

Applicant's summary and conclusion

Executive summary:

Based on the physicochemical properties of ptBP alone [i.e., low molecular weight (150.22 g/mol), low Kow value (3.29), and high water solubility (610 mg/L)], the absorption of ptBP from various routes of exposure is expected to be 100%. Consistent with this assumption, ptBP has been demonstrated to be absorbed following oral administration as determined in rats. Signs of toxicity observed in experimental animals following oral exposure to ptBP also are indicative of systemic absorption. An oral absorption percentage of 100% is applied to ptBP based on in vivo animal data showing elimination of a substantial amount of an orally administered dose (147 µg/kg body weight/day for 3 days) via urine and feces at levels of 72.9% and 26.7%, respectively; whether the material detected in fecal samples occurred as unabsorbed ptBP or as ptBP metabolites eliminated via bile was not determined. Although, no systemic toxicity was observed in experimental animals upon acute dermal exposure, the results of human biomonitoring studies have demonstrated that ptBP is systemically absorbed intact following dermal, as well as inhalational exposures. Data specifically addressing the percentage of absorption from inhalational and dermal exposure are lacking, and therefore, a default absorption value of 100% is considered for ptBP. Whether ptBP would be expected to cross the placental barrier cannot be deduced from the reproductive toxicity study conducted in rats.

Following oral absorption, a small amount of the compound is distributed to the liver in rats, but not to adipose tissue or lungs. Biomonitoring of urine samples from workers handling ptBP indicate that ptBP is metabolized to hydrolysed sulphate and glucuronide conjugates, which is consistent within vivo animal data, as well as in vitro data. Elimination of ptBP conjugates occurs predominantly via the urine, but also occurs in the feces as demonstrated in rats. As mentioned, whether the material detected in rat fecal samples occurred as unabsorbed ptBP or as ptBP metabolites eliminated via bile was not determined in that particular study; however, additional data show that ptBP metabolites are eliminated in the bile to some extent in rats. Taking into consideration the high water solubility of the compound and the extent of phase II metabolism, ptBP is not expected to bioaccumulate. Instead, the retention of ptBP in rats has been shown to be negligible at 0.1% 7 days after an oral dose of ptBP (147 µg/kg body weight/day for 3 days). Moreover, urinary ptBP levels detected following occupational exposure were observed to decrease when workers were away from the workplace, with metabolites eliminated from the urine within 24 hours. The biological half-life of ptBP in urine was calculated to be 4 hours.