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Description of key information

PAH are absorbed rapidly through the pulmonary tract, the gastrointestinal tract and to a much lesser extent through skin. Metabolism is complex resulting mostly in hydroxylated species which in part may further be conjugated. Excretion is via urine, bile and faeces. Conjugates excreted into bile can be hydrolysed in the gut and be reabsorbed.
Absorption through human skin will be not more than 2 % within and after 8 h of exposure. Permeation through rat skin is much more pronounced (ca. 8 fold) compared to human skin.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - dermal (%):
2

Additional information

Distillates (coal tar), heavy oils (anthracene oil high (> 50 ppm) BaP, AOH) [CAS no. 90640-86-1] is a UVCB and consists of a complex combination of polycyclic aromatic hydrocarbons (PAH).It comprises mainly 3- and 4-ring aromatic compounds and to a much lesser extent PAHs with 5 rings (see Chapter 1.). Main components are phenanthrene, anthracene (3-ring PAH), fluoranthene, pyrene, benz[a]anthracene, and chrysene (4-ringPAH) each accounting for ca. 3 to 10 %.The majority of other components of AOH fall within the molecular size range of these five substances.Benzo[a]pyrene (5-ring PAH) is present at a typical concentration distinctly below 1 % (typical concentration) representing PAH with 5-rings and more.

3- and 4-ring PAH together represent approx. 30 % of total AOH.The accumulated percentage of all substances that can analytically be identified is about 50 - 53 % (average ca. 51%), depending on individual AOH samples and analytical method used. The remainder of AOH is not structurally known. Identification was not possible applying standard analytical methods.

Toxicokinetics

As AOH basically is composed of PAH, toxicokinetics of these substance class will determine the toxicokinetic properties of total AOH.AOH toxicokinetics can largely be characterised based on information determined for its PAH constituents. Toxicokinetic characteristics of PAH are reported based on a Summary from WHO 1998/2003

Absorption

PAH are absorbed through the pulmonary tract, the gastrointestinal tract, and the skin.Degree of absorption may be different for individual substances.The rate of absorption from the lungs depends on the type of PAH, the size of the particles on which they are adsorbed, and the composition of the adsorbent. PAH adsorbed onto particulate matter are cleared from the lungs more slowly than free hydrocarbons.

Gastrointestinal absorption in rodents has been reported to be up to 90 % (Grimmer et al. 1991). Effective absorption by the different routes is also evidenced by observation of systemic toxicity following exposure by the different routes.Absorption from the gastrointestinal tract occurs rapidly in rodents, the majority of metabolites released into the intestine via biliary excretion.

Distribution

PAH are widely distributed throughout the organism after administration by any route and are found in almost all internal organs, but particularly those rich in lipids. Intravenously injected PAH are cleared rapidly from the bloodstream of rodents but can cross the placental barrier and have been detected in foetal tissues.

Studies with 32P-postlabelling for the detection of DNA-adducts after percutaneous absorption of mixtures of PAH in rodents showed that components of the mixtures reach the lungs, where they become bound to DNA.

Metabolism

The metabolism of PAH to more water-soluble derivatives, which is a prerequisite for their excretion, is complex. In general, parent compounds are converted into intermediate epoxides (a reaction catalysed by cytochrome P450-dependent mono-oxygenases), which are further transformed by rearrangement or hydration to yield phenols or diols.In following steps conjugation by glutathione, sulphate or glucuronic acid may occur. Alternatively or in addition, a second oxidation at another position of the aromatic system is possible to yield tetrols, which can themselves be conjugated with sulphuric or glucuronic acids or with glutathione. Most metabolism results in detoxification, but some PAH are activated to DNA-binding species, principally diol epoxides, which may initiate tumours.

For phenanthrene only approx. 3.8 % of the excreted dose were detected as hydroxy-phenanthrenes (1-, 2-position ca. 60 % of total OH-derivatives, 3-, 4-, and 9-position minor). Dihydro-diols were not detected and may have escaped determination (Grimmer et al. 1991). In an experiment with liver microsomes from untreated rats (Jacob et al. 1982), trans 9-,10-dihydro-diol was identified (K-region oxidation) indicating that hydroxy-derivatives of phenanthrene can be formed other than recovered in the study of Grimmer et al. 1991

Excretion

PAH metabolites and their conjugates are excreted via the urine and faeces, but conjugates excreted into the bile can be hydrolysed by enzymes of the gut flora and be reabsorbed. It can be inferred from the available information on the total human body burden that PAH do not persist in the body and that turnover is rapid. This inference excludes those PAH moieties that become covalently bound to tissue constituents, in particular nucleic acids, and are not removed by repair.

References

WHO (1998). Selected non-heterocyclic polycyclic aromatic hydrocarbons. Environmental Health Criteria 202, Geneva, Switzerland, WHO (World Health Organisation) 1998

WHO (2003). HEALTH RISKS OF PERSISTENT ORGANIC POLLUTANTS FROM LONG-RANGE TRANSBOUNDARY AIR POLLUTION, JOINT WHO/CONVENTION TASK FORCE ON THE HEALTH ASPECTS OF AIR POLLUTION. WHO Regional Office for Europe, World Health Organization 2003

Dermal absorption

In synopsis of observations from comparative in-vivo and in-vitro studies (human vs. rodent) on spiked creosote, it is expected that not more than 2 % of a dermal dose will be absorbed through human skin within and after 8 hours of exposure (Fasano 2007a,b). The conversion factor human vs. rat skin was found to be 0.12, which means that the dermal dose absorbable within 8 hours is about 8-fold higher in rat than in human skin.

Studies of Van Rooij et al. 1995 and Sartorelli et al. 1999 show that lower molecular weight PAH are absorbed faster than higher molecular weight PAH. For absorption through pig ear (Van Rooij) and full thickness skin from the abdomen of monkeys (Ceropithecus aetops) (application in artificial sweat) (Sartorelli), differences in absorption rates from 103 ng/(h*cm²) (phenanthrene) to 0.8 ng/(h*cm²) (benzo[a]pyrene) and from 24 ng/(h*cm²) (fluorene) to 0.4 ng/(h*cm²) (benzo[a]pyrene), respectively, were observed.

Taking into account the PAH composition of AOH (more higher size PAH compared to creosote) it can be estimated that human dermal absorption of AOH will at least not be higher than for creosote (Fasano, 2007a,b).