Pyrocatechol

Endpoint summary

Additional information

Different publications are available to evaluate the toxicokinetics of catechol. Main studies were not performed according to standard guidelines but gave information about distribution, metabolisation, excretion, and enzymatic oxidation of catechol.

Distribution:

In one publication of Hwang (1982) and 2 publications of Greenlee (1981), the distribution of catechol was investigated in in vivo studies which were considered as validity 2, according to Klimish scales.

- [3H] catechol was used to follow the kinetics and metabolic fate of inhaled catechol in cigarette smoke in Mice. 2 to 2.3 µCi [3H] catechol were present in reconstituted cigarette. Catechol is rapidly absorbed, redistributed, and excreted from mice exposed to whole cigarette smoke (Hwang,1982).

- [14C] Catechol in saline solution were administered into the lateral vein of male rats at concentration of 1.2 mg/kg alone or with simultaneous administration with non labelled catechol at dose of 12 mg/kg bw. It was shown that, the radioactivity was concentrated in the bone marrow and lymphoid organs (Greenlee,1981).

- [14C] Catechol was administered for 2 hours into the lateral vein of male rats at concentration of 14 mg/kg in rats pre-treated or not five days prior with 500 mg/kg ip injection of Arochlor 1254 solution in corn oil. The measurement of covalently bound radioactivity indicated that the pre-treatment with Aroclor decrease the amount of radioactivity found in the bone marrow and white blood cell. Catechol did not spontaneously autoxidise but generated the formation of O2. Catechol did not increase NADPH oxidation. (Greenlee,1981).

After inhalation exposure, catechol was rapidly absorbed and found in the blood, lung, and eliminated via urine. Catechol was rapidly eliminated via urine after inhalation exposure (half-life 3 -7h) and seemed to no potentially bioaccumulate in Human.

 

Metabolisation :

In in vitro study of Anderson (1968) of validity 2, catechol was shown to be substrate for the rat liver enzyme named: catechol-o-methytransferase (COMT) which transfers methyl group forming o-methylated products. The catechol could enter in competition with other substrate of this enzyme presents in mammalian tissue.

Metabolisation data on catechol indicated that catechol react with liver metabolic enzyme system (catechol-o-methytransferase (COMT) which transfers methyl group forming o-methylated products).

Catechol did not spontaneously autoxidise but generated the formation of O₂.

 

Excretion:

Five in vivo studies of validity 2 evaluated in different species the excretion of Catechol after inhalation, infusion in renal portal circulation or oral administration.

Hirosawa (1976), analysed the presence of catechol in urines of 13 workers of a factory where phenols were produced. Men were exposed 7-9h per day for 2 years to vapours of catechol at 1.8 ppb and occasionally 70 ppb, and phenol.The biological half-life of catechol measured was 3 -7h, similar than for phenol.

Regarding result obtained in this study, catechol was rapidly eliminated via urine after inhalation exposure (half-life 3 -7h) and seemed to no potentially bioaccumulate in Human.

In another in vivo study of Garton (1949) on Rabbits, excretion of the different metabolites of catechol had been characterized: rabbits were given catechol orally, at the dose of 100 mg catechol/kg and the urine was collected over 24 h. Catechol metabolites where determined by different methods.

70 % of orally administered catechol was excreted in 24 h conjugated with glucuronic acid and 18% conjugated with sulphuric acid. A small amount, ca 2%, is excreted in thefree state. Some catechol is also oxidised to hydroxyquinol, which appears in the urine as ethereal sulphate. The catechol glucuronide has been proved to be a monoglucuronide, by conversion into crystalline o-methoxyphenyltriacetyl glucuronide methyl ester which on hydrolysis yields guaiacol. Evidence was also presented to show that the ethereal sulphate of catechol formed in the rabbit is a monosulphate.

- In a an in vivo study of La Voie (1985), Urine analyses were performed as a part of a carcinogenesis study (see Chapter 5.7) where 0.05% catechol was administered in drinking water for 78 weeks (3.99 gcatechol/animal administered during the bioassay) to a group of 30 rats.

Analysis of the urine of rats, revealed that > 99% of the catechol present was in the form of glucuronide or sulphate conjugates. The amount of conjugated catechol excreted as determined in two separate assays was 2.4-2.5 mg/rat per day. 

In contrast to these results, the level of free catechol detected in these urine samples was 7.1-18.5 µg per rat per day. Rats receiving tap water alone were found to excrete a total of approximately 35.5 µg of catechol per day. In this group less than 7.0 µg of catechol was excreted per day in its free form.

In vivo data on excretion revealed that 70 % of orally administered catechol in rabbit was excreted in 24 h conjugated with glucuronic acid and 18% conjugated with sulphuric acid. A small amount, ca 2%, is excreted in thefree state. Some catechol is also oxidised to hydroxyquinol, which appears in the urine as ethereal sulphate. Same metabolisation was observed in rats.

 

Enzymatic oxidation:

One in vitro study of validity 2, was performed with catechol in the presence of polyphenol oxidase. The oxidation of catechol has been investigated using paper chromatographic methods together with manometric.

Under conditions of very low substrate concentration and optimum oxygen uptake the only intermediate which can be detected is a purple-red pigment.

At higher substrate concentrations the three isometric tetrahydroxy phenyls are formed plus the purple-red pigment plus the non-phenolic yelow component (yellow quinone). These compounds can also be prepared from catechol with inorganic oxidants.

The tetrahydroxydiphenyls only consume half the oxygen per aromatic ring compared to catechol and their production in varying amounts at different concentrations of catechol may explain the divergence in reported oxygen uptakes.

 

Dermal absorption:

The percutaneous penetration of Catechol in an aqueous solution, was determined in vitro using split-thickness skin membranes from human skin (Hassler, 2005) .

The skin membranes were set up in flow-through diffusion cells and [14C] Catechol was applied onto the skin membranes at a concentration of 1 mg/cm³. Catechol penetrated to a very low extent through human skin membranes, only 0.04% and 0.22% penetrated within 10 and 60 minutes respectively. The permeability constant Kp for Catechol was calculated to be 1.430 x10^-3cm/h.