Diphenyl carbonate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Assessment based on physico-chemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed

Type of information:

other: Assessment based on physico-chemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The toxicokinetic assessment of diphenyl carbonate is based on physico-chemical properties of the compound and on toxicological data. Experimental toxicokinetic studies were not performed.

Principles of method if other than guideline:

Statement on toxicokinetics

Description of key information

The following remarks on the toxicokinetics of diphenyl carbonate are based on physico-chemical properties of the compound and on toxicological data. Inhalation exposure to the vapour is expected to be negligible. Subsequent to oral ingestion, intestinal absorption is observed. Toxicological experiments did not point to a relevant dermal absorption. Diphenyl carbonate is expected to be widely distributed throughout the body. DNA-reactive metabolites of diphenyl carbonate will most probably not be generated in mammals in the course of hepatic biotransformation.

Key value for chemical safety assessment

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

25

Absorption rate - inhalation (%):

100

Additional information

The following remarks on the toxicokinetics of diphenyl carbonate are based on physico-chemical properties of the compound and on toxicological data (Tegethoff, 2008). Experimental toxicokinetic studies were not performed.

 

Diphenyl carbonate is a solid with a very low vapour pressure under normal ambient conditions (0.014 Pa); therefore inhalation exposure to the vapour is expected to be negligible. Diphenyl carbonate (molecular mass of 214 g/mole) has a moderate to low solubility in water (13 mg/L). Its log Pow of 3.28 and its solubility in organic solvents suggest intestinal absorption subsequent to oral ingestion. This assumption is confirmed by the results of acute and repeated dose oral toxicity studies, indicating bioavailability of the compound by showing dose related toxic effects with an LD50 of 1500 mg/kg bw/day in rats after acute exposure (FitzGerald, 1990) and at doses of ≥ 427 mg/kg bw/day (LOAEL) in male rats and ≥ 219 mg/kg bw/day (LOAEL) in female rats after repeated exposure (Eiben, 2003a).

 

Molecular weight, log Pow and lipophilicity of diphenyl carbonate indicate that absorption through the skin after dermal exposure is likely. However, toxicological experiments did not point to a relevant dermal absorption. After dermal treatment of rats with 2000 mg/kg bw for 24 hours under occlusive conditions no signs of systemic or local toxicity were observed (Krötlinger, 1999), whereas this dose led to marked toxicity via the oral route (FitzGerald, 1990).

 

Diphenyl carbonate is expected to be widely distributed throughout the body. Signs of toxicity became obvious in the liver, adrenals and ovaries of rats after repeated oral exposure (Eiben, 2003a; Eiben, 2003b). Clonic convulsions after oral administration of high diphenyl carbonate doses indicate access to the central nervous system (FitzGerald, 1990 and Eiben, 2002). Based on the results of several in vitro genotoxicity tests (Ames-Tests: Timm, 1989; Loveday, 1991; gene mutation assay: Wollny, 1996; chromosomal aberration assay: Czich, 1996, all performed with and without metabolic activation) it is concluded that DNA-reactive metabolites of diphenyl carbonate will most probably not be generated in mammals in the course of hepatic biotransformation. This conclusion is confirmed in vivo by negative results obtained in two mouse micronucleus tests (Völkner, 2000; Herbold, 1999) and in the in vivo UDS test on rat liver (San, 2002).

In the absence of quantitative experimental data, inhalation absrobtion is set to the default value of 100%, oral absorption to 50%, and dermal absorption to 25% in line with current EFSA guidance on the dermal of absorption of materials in the absence of data.