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:

other: Study meets generally accepted scientific standards, well documented, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

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

Author:

Van Rooij JGM, Vinke E, De Lange J, Bruijnzeel PL, 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:

Tar, coal, high-temp.

EC Number:

266-024-0

EC Name:

Tar, coal, high-temp.

Cas Number:

65996-89-6

IUPAC Name:

65996-89-6

Details on test material:

- Name of test material (as cited in study report): Coal tar
- Substance type: organic
- Physical state: liquid, viscous
- Composition and analytical limits

Coal tar, industrial, from ACSZ/NL which contained the test PAH in the following concentrations:

Content Detection limit
in coal tar [%] [pmol/ml blood]
=====================================
fluorene 2.1 53.0
phenanthrene 6.8 1.7
anthracene 3.7 2.0
fluoranthene 4.0 51.0
pyrene 2.1 2.7
benzo[b]fluoranthene 0.9 7.8
benzo[k]fluoranthene 0.4 0.3
BaP 0.9 6.3
indeno[123-cd]pyrene 0.6 8.3
dibenzo[ah]anthracene 0.4 16.5
=====================================

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
-


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):


IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Duration of exposure:

average perfusion time: 250 min

Doses:

~11 mg tar/cm2 [100 %]

Content Single PAH dose
in coal tar [%] [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
BaP 0.9 90
indeno[123-cd]pyrene 0.6 66
dibenzo[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

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)
- Limits of detection and quantification: see above under dose

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.


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 at 30 °C with heparinized pig blood collected from the pigs.
Coal tar was applied to a skin area of 6x4 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:

see also above "Details of Study Design"
- Limit of detection (LOD): see under "Doses"

Conversion factor human vs. animal skin:

no data

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*cm^2)	ng/(h*cm^2)
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	--
BaP	3	approx. 0.8
indeno[123-cd]pyrene	1	--
dibenzo[ah]anthracene	1	--

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.