Pitch, coal tar, high-temp.

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Dermal Absorption of Polycyclic Aromatic Hydrocarbons in the Blood-perfused Pig Ear

Author:

VanRooij JGM, Vinke E, De Lange J, Bruijnzeel PLB, Bodelier-Bade MM, Noordhoek J, Jongeneelen FJ

Year:

1995

Bibliographic source:

J. Appl. Toxicol. 15, 193-200

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Skin model/in-vitro blood perfusion model: by de Lange et al. 1991, J. Pharmacol. Toxicol. Methods 27 71-77

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Coal tar

Molecular formula:

not applicalbe

IUPAC Name:

Coal tar

Test material form:

liquid: viscous

Specific details on test material used for the study:

- Name of test material (as cited in study report): coal tar
- Physical state: liquid, viscous

Radiolabelling:

no

Test animals

Species:

pig

Strain:

other: domestic

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Slaughterhouse: no details
- Weight at study initiation: 75 - 100 kg
- Experimental conditions: only skin samples (ear) of the animals were used in the in-vitro dermal absorption experiment

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Duration of exposure:

average perfusion time: 250 min

Doses:

~11 mg coal tar/cm² [100 %]
==============================
Substance: Content in coal tar [%] / Single PAH dose [µg/cm²];
fluorene: 2.1 / 230 ;
phenanthrene: 6.8 / 750 ;
anthracene: 3.7 / 410 ;
fluoranthene: 4.0 / 440 ;
pyrene: 2.1 / 230 ;
benzo[b]fluoranthene: 0.9 / 90 ;
benzo[k]fluoranthene: 0.4 / 44 ;
benzo[a]pyrene: 0.9 / 90 ;
indeno[123-cd]pyrene: 0.6 / 66 ;
dibenz[ah]anthracene: 0.4 / 44 ;

Total: ~22 % / ~2400 µg/cm²
==============================

No. of animals per group:

5 pig ears per treatment

Control animals:

no

Details on study design:

DOSE PREPARATION
not applicable, neat substance tested

APPLICATION OF DOSE: topical to the ear

VEHICLE: not applicable

TEST SITE
- Preparation of test site: no particular action
- Area of exposure: 6 x 4 cm²
- Type of cover / wrap if used: none

REMOVAL OF TEST SUBSTANCE
- Perfusion: until perfusion pressure became too high (> 70 mm Hg), max. 250 min
- Removal of protecting device: not relevant
- Washing procedures and type of cleansing agent: not relevant, termination of test
- Time after start of exposure: max. 250 min

SAMPLE COLLECTION
- Collection of blood: 200 min, for pyrene: complete kinetics with 10 - 11 time intervals up to 200 - 250 min

ANALYSIS
- Blood samples (10 ml): Reversed-phase HPLC after 3-fold extraction with n-hexane, evaporation of the solvent and re-dissolution of the residues in methanol (2 ml)
- The method for analysis of the 10 PAHs has an average coefficient of variation of 14.4 %
- Recovery ranged from 45 % for dibenzo[a]anthracene to 97 % for anthracene
- Limits of detection:
[pmol/ml blood]
===============================
fluorene 53.0
phenanthrene 1.7
anthracene 2.0
fluoranthene 51.0
pyrene 2.7
benzo[b]fluoranthene 7.8
benzo[k]fluoranthene 0.3
benzo[a]pyrene 6.3
indeno[123-cd]pyrene 8.3
dibenzo[ah]anthracene 16.5
===============================

STATISTICS:
Paired t-test to determine whether the dermal absorption of the various PAH was statistically different from pyrene absorption

Details on in vitro test system (if applicable):

In-vitro blood perfusion model:
Five ears from domestic pigs were used to study the uptake of 10 PAH in blood after coal-tar application.
The treatment started after 30 min pre-perfusion with oxygenated blood. Perfusion was carried out at 30 °C with heparinized pig blood collected from the pigs.
Coal tar was applied to a skin area of 6 x 4 cm² with an average dose of 11 mg/cm².
Simultaneously, functional control measurements were conducted to assure the physiological integrity of the organ, including blood pressure, blood flow, and glucose uptake.

Results and discussion

Total recovery:

It is not reasonable to estimate total recovery in relation to an applied dose, because the test material was highly overdosed. But owing to the high dosage, the measured fluxes can be supposed to be maximum absorption rates.
==============================
Initial absorption rates of 10 PAHs from coal tar applied to the perfused pig ear:

(Absorption flux at 200 min p.a.)
----------------------------------------------------
Substance: [pmol/(h*cm²)] / [ng/(h*cm²)];
----------------------------------------------------
fluorene: 430 / approx. 71;
phenanthrene: 580 / approx. 103;
anthracene: 110 / approx. 19.5;
fluoranthene: 105 / approx. 21;
pyrene: 60 / approx. 12;
benzo[b]fluoranthene: 3 / approx. 0.8;
benzo[k]fluoranthene: 1 / -- ;
benzo[a]pyrene: 3 / approx. 0.8;
indeno[123-cd]pyrene: 1 / -- ;
dibenzo[ah]anthracene: 1 / --
==============================

Percutaneous absorption

Percutaneous absorption 1

Key result

Time point:

200 min

Dose:

11 mg coal tar (750 µg phenanthrene)/cm²

Parameter:

rate

Absorption:

ca. 103 other: ng/(h*cm²)

Remarks on result:

other: absorption rate for phenanthrene

Percutaneous absorption 2

Key result

Time point:

200 min

Dose:

11 mg coal tar (230 µg fluorene)/cm²

Parameter:

rate

Absorption:

ca. 71 other: ng/(h*cm²)

Remarks on result:

other: absorption rate for fluorene

Percutaneous absorption 3

Key result

Time point:

200 min

Dose:

11 mg coal tar (440 µg fluoranthene)/cm²

Parameter:

rate

Absorption:

ca. 21 other: ng/(h*cm²)

Remarks on result:

other: absorption rate for fluoranthene

Percutaneous absorption 4

Key result

Time point:

200 min

Dose:

11 mg coal tar (410 µg anthracene)/cm²

Parameter:

rate

Absorption:

ca. 19.5 other: ng/(h*cm²)

Remarks on result:

other: absorption rate for anthracene

Percutaneous absorption 5

Key result

Time point:

200 min

Dose:

11 mg coal tar (230 µg pyrene)/cm²

Parameter:

rate

Absorption:

ca. 12 other: ng/(h*cm²)

Remarks on result:

other: absorption rate for pyrene

Percutaneous absorption 6

Key result

Time point:

200 min

Dose:

11 mg coal tar (90 µg benzo[a]pyrene)/cm²

Parameter:

rate

Absorption:

ca. 0.76 other: ng/(h*cm²)

Remarks on result:

other: absorption rate for benzo[a]pyrene)

Percutaneous absorption 7

Key result

Time point:

200 min

Dose:

11 mg coal tar (44 µg dibenz[ah]anthracene)/cm²

Parameter:

rate

Absorption:

ca. 0.28 other: ng/(h*cm²)

Remarks on result:

other: absorption rate for dibenz[ah]anthracene

Conversion factor human vs. animal skin:

not applicable

Any other information on results incl. tables

Initial absorption rates of 10 PAHs from coal tar applied to the perfused pig ear

 

	Absorption fluxes at 200 min p.a.
	pmol/(h*cm²)	ng/(h*cm²)
Fluorene	430	approx. 71
Phenanthrene	580	approx. 103
Anthracene	110	approx. 19.5
Fluoranthene	105	approx. 21
Pyrene	60	approx. 12
Benzo[b]fluoranthene	3	approx. 0.76
Benzo[k]fluoranthene	1	approx. 0.25
Benzo[a]pyrene	3	approx. 0.76
Indeno[1,2,3-cd]pyrene	1	approx. 0.28
Dibenz[a,h]anthracene	1	approx. 0.28

 

The mean absorption fluxes [pmol/(h*cm²)] at 200 min after application of coal tar varied strongly between the 10 PAH.

Furthermore, variation between ears was high, too: for pyrene, for example, the flux ranged between 6 and 155 pmol/(h*cm²) and the cumulative uptake after 200 min was between 26 and 193 pmol/cm². This was not caused by differences in dosing: applied amounts were high overdoses, because 0.2 % of each PAH was absorbed through the skin after 200 min.

The relative cumulative uptake (in relation to pyrene) was 0.01 for indeno[123-cd]pyrene to 12 for phenanthrene, for each PAH except fluoranthene, statistically different from pyrene uptake (p= 0.01). The inter-ear variation was relatively small when the absorbed amount was related to pyrene, indicating that the relative absorption fluxes of the various PAH were quite constant.