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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics, other
Remarks:
in vivo and in vitro
Type of information:
experimental study
Remarks:
information comes from a comprehensive report summarising properties, toxicological/ecotoxicological effects, and effects on humans and the environment of a variety of polycyclic aromatic hydrocarbons
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-heterocyclic polycyclic aromatic hydrocarbons - IPCS Environmental Health Criteria 202 (§)
Author:
WHO
Year:
1998
Bibliographic source:
International Programme on Chemical Safety (IPCS), WHO - World Health Organization, Geneva, Switzerland

Materials and methods

Objective of study:
other: various objectives
Principles of method if other than guideline:
Review on PAHs summarising data peer-reviewed by a group of international experts
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Naphthalene
EC Number:
202-049-5
EC Name:
Naphthalene
Cas Number:
91-20-3
Molecular formula:
C10H8
IUPAC Name:
Naphthalene
Constituent 2
Chemical structure
Reference substance name:
1-methylnaphthalene
EC Number:
201-966-8
EC Name:
1-methylnaphthalene
Cas Number:
90-12-0
Molecular formula:
C11H10
IUPAC Name:
1-methylnaphthalene
Constituent 3
Chemical structure
Reference substance name:
Acenaphthene
EC Number:
201-469-6
EC Name:
Acenaphthene
Cas Number:
83-32-9
Molecular formula:
C12H10
IUPAC Name:
1,2-dihydroacenaphthylene
Constituent 4
Chemical structure
Reference substance name:
Fluorene
EC Number:
201-695-5
EC Name:
Fluorene
Cas Number:
86-73-7
Molecular formula:
C13H10
IUPAC Name:
9H-fluorene
Constituent 5
Chemical structure
Reference substance name:
Anthracene
EC Number:
204-371-1
EC Name:
Anthracene
Cas Number:
120-12-7
Molecular formula:
C14H10
IUPAC Name:
anthracene
Constituent 6
Chemical structure
Reference substance name:
Phenanthrene
EC Number:
201-581-5
EC Name:
Phenanthrene
Cas Number:
85-01-8
Molecular formula:
C14H10
IUPAC Name:
phenanthrene
Constituent 7
Chemical structure
Reference substance name:
Fluoranthene
EC Number:
205-912-4
EC Name:
Fluoranthene
Cas Number:
206-44-0
Molecular formula:
C16H10
IUPAC Name:
fluoranthene
Constituent 8
Chemical structure
Reference substance name:
Pyrene
EC Number:
204-927-3
EC Name:
Pyrene
Cas Number:
129-00-0
Molecular formula:
C16H10
IUPAC Name:
pyrene
Constituent 9
Chemical structure
Reference substance name:
Benz[a]anthracene
EC Number:
200-280-6
EC Name:
Benz[a]anthracene
Cas Number:
56-55-3
Molecular formula:
C18H12
IUPAC Name:
tetraphene
Constituent 10
Chemical structure
Reference substance name:
7,12-dimethylbenz[a]anthracene
EC Number:
200-359-5
EC Name:
7,12-dimethylbenz[a]anthracene
Cas Number:
57-97-6
Molecular formula:
C20H16
IUPAC Name:
7,12-dimethyltetraphene
Constituent 11
Chemical structure
Reference substance name:
Chrysene
EC Number:
205-923-4
EC Name:
Chrysene
Cas Number:
218-01-9
Molecular formula:
C18H12
IUPAC Name:
chrysene
Constituent 12
Chemical structure
Reference substance name:
Benzo[e]acephenanthrylene
EC Number:
205-911-9
EC Name:
Benzo[e]acephenanthrylene
Cas Number:
205-99-2
Molecular formula:
C20H12
IUPAC Name:
benzo[e]acephenanthrylene
Constituent 13
Chemical structure
Reference substance name:
Benzo[k]fluoranthene
EC Number:
205-916-6
EC Name:
Benzo[k]fluoranthene
Cas Number:
207-08-9
Molecular formula:
C20H12
IUPAC Name:
benzo[k]fluoranthene
Constituent 14
Chemical structure
Reference substance name:
Benzo[def]chrysene
EC Number:
200-028-5
EC Name:
Benzo[def]chrysene
Cas Number:
50-32-8
Molecular formula:
C20H12
IUPAC Name:
benzo[pqr]tetraphene
Constituent 15
Chemical structure
Reference substance name:
Dibenz[a,h]anthracene
EC Number:
200-181-8
EC Name:
Dibenz[a,h]anthracene
Cas Number:
53-70-3
Molecular formula:
C22H14
IUPAC Name:
benzo[k]tetraphene
Constituent 16
Chemical structure
Reference substance name:
Indeno[1,2,3-cd]pyrene
EC Number:
205-893-2
EC Name:
Indeno[1,2,3-cd]pyrene
Cas Number:
193-39-5
Molecular formula:
C22H12
IUPAC Name:
indeno[1,2,3-cd]pyrene
Constituent 17
Chemical structure
Reference substance name:
Benzo[ghi]perylene
EC Number:
205-883-8
EC Name:
Benzo[ghi]perylene
Cas Number:
191-24-2
Molecular formula:
C22H12
IUPAC Name:
benzo[ghi]perylene
Constituent 18
Chemical structure
Reference substance name:
Benzo(r,s,t)pentaphene
EC Number:
205-877-5
EC Name:
Benzo(r,s,t)pentaphene
Cas Number:
189-55-9
Molecular formula:
C24H14
IUPAC Name:
benzo[rst]pentaphene
Test material form:
solid
Details on test material:
- Individual test substances (PAH) are reported in the specific study records.
- Substances were applied individually or combined as mixtures (for details see study record).
Specific details on test material used for the study:
PAH consisting of four and more condensed aromatic ring systems are relevant components of CTPht. Their properties and toxicokinetic behaviour are used for the characterisation of the toxicokinetic properties of CTPht.

Test animals

Species:
other: various

Administration / exposure

Route of administration:
other: oral, dermal, inhalation

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
PAH are absorbed through the pulmonary tract, the gastrointestinal tract, and the skin. Absorption rate from lung depends on type of PAH. Gastrointestinal absorption is rapid in rodents with metabolites returning to the intestine via biliary excretion.
Type:
distribution
Results:
PAH are widely distributed throughout the organism after administration by any route and are found in almost all internal organs, but particularly in those rich in lipids.
Type:
metabolism
Results:
Metabolism is via intermediary epoxides that are further transformed by rearrangement or hydration to phenols or dihydrodiols. Secondary oxidation yield tetrols. Hydroxylated metabolites can be conjugated with sulphuric or glucuronic acid, or glutathione.
Type:
excretion
Results:
PAH metabolites and their conjugates are excreted via the urine and faeces. Conjugates may be hydrolysed by gut flora after biliary excretion and be reabsorbed. With increasing size, excretion into faeces increases. PAH seem not to persist in the body.

Applicant's summary and conclusion

Executive 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 with 32P-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 varies 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 foetal 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-dependent mono-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 tissue constituents, in particular nucleic acids, and that are not removed by repair.