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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other:
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Review, peer-reviewed data

Data source

Reference
Reference Type:
review article or handbook
Title:
Selected non-hetrocyclic polycyclic aromatic hydrocarbons.
Author:
WHO
Year:
1998
Bibliographic source:
Environmental Health Criteria 202, Geneva, Switzerland, WHO (World Health Organisation) 1998

Materials and methods

Principles of method if other than guideline:
Review on PAHs
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: various

Administration / exposure

Route of administration:
other: oral, dermal, inhalation

Results and discussion

Applicant's summary and conclusion

Executive summary:

SUMMARY

PAH are absorbed through the pulmonary tract, the gastrointestinal tract, and the skin. The rate of absorption from the lungs depends on the type of PAH, the size of the particles on which they are absorbed, and the composition of the adsorbent. PAH adsorbed onto particulate matter are cleared from the lungs more slowly than free hydrocarbons. Absorption from the gastrointestinal tract occurs rapidly in rodents, but metabolites return to the intestine via biliary excretion. Studies with32P-postlabelling of percutaneous absorption of mixtures of PAH in rodents showed that components of the mixtures reach the lungs, where they become bound to DNA. The rate of percutaneous absorption in mice according to the compound.

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 fetal tissues.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-dependentmono-oxygenases), which are further transformed by rearrangement or hydration to yield phenols or diols and – following secondary oxidation - to yield tetrols, which can themselves be conjugated with sulfuric or glucuronic acids or with glutathione. Most metabolism results in detoxification, but some PAH are activated to DNA-binding species, principally diol epoxides, which can initiate tumours.

PAH metabolites and their conjugates are excreted via the urine and faeces, but conjugates excreted in the bile can be hydrolysed by enzymes of the gut flora and 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 tissueconstituents, in particular nucleic acids, and are not removed by repair.