Tar, coal, high-temp.

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in 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:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Experimental photo-toxicity test on humans, objectives: determination of the minimal UVA dose required to induce delayed erythema (minimal phototoxic dose) and the minimal UVA dose required to induce an immediate smarting reaction (minimal smarting dose).

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

8007-45-2

Cas Number:

8007-45-2

IUPAC Name:

8007-45-2

Constituent 2

Reference substance name:

tar, coal

IUPAC Name:

tar, coal

Details on test material:

- Name of test material (as cited in study report): crude coal tar (CCT)
- Molecular formula (if other than submission substance): not applicable, complex mixture
- Molecular weight (if other than submission substance): not applicable, complex mixture
- Substance type: organic- Physical state: liquid, viscous
- Composition of test material, percentage of components: aromatic hydrocarbons, no data

Specific details on test material used for the study:

Crude coal tar (CCT), not further specified:
- Name of test material (as cited in study report): crude coal tar (CCT)
- Molecular formula (if other than submission substance): not applicable, complex mixture
- Molecular weight (if other than submission substance): not applicable, complex mixture
- Substance type: organic- Physical state: liquid, viscous
- Composition of test material, percentage of components: aromatic hydrocarbons, no data

Test animals

Species:

human

Strain:

other: adults, untanned skin (skin type I - III)

Details on test animals or test system and environmental conditions:

volunteers: no history of photosensitivity / not sensitised

Test system

Type of coverage:

open

Preparation of test site:

not specified

Vehicle:

other: petrolatum

Controls:

other:

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): 5 %

VEHICLE
- Amount(s) applied (volume or weight with unit): no data

Duration of treatment / exposure:

Exposure time to tar were 15, 30, 60, 90, 120, and 180 min for the determination of the corresponding MPD (Minimal Phototoxic UV-Dose with related to irradiation time needed) (Report Fig. 2 and 3).
As standard, 1h-exposure to tar was used for determining effective UV-doses (minimal erytjhema, minimal phototoxic, and minimal smarting doses).

Observation period:

24 h post application

Number of animals:

- 8 volunteers examined (out of 32 in total for several test settings) for MPD in relation to tar-exposure time (report, Fig 2 and 3).
- Variable number of volunteers in groups from N = 6 to 19 (report, Fig. 4) for determination of specific latency time intervals after removal of the tar, using the MSD of UV radation.

Details on study design:

TEST SITE
- Area of exposure: 1-cm diameter aperture for light source.
- Number of sites per individual: 6 separate sites on the backs of 8 subjects
- Type of wrap if used: none

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Ivory soap, water
- Time after start of exposure: 15, 30, 60, 90, 120, and 180 min
- Time of UVA exposure: 4 - 60 min - The UV irradiation started after exposure to and removal of tar.

SCORING SYSTEM: no data, probably Draize score (The minimal phototoxic dose was defined as the minimal UVA dose causing 1+ erythema with distinct borders read at 24 h after exposure.)

STATISTICS: Student´s test was used to compare sample means between two samples, and analysios of varience was used to test differences in means between multiple samples. Linear (least squares) regression analysis was used to study the relation between variables.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

minimal phototoxic effect (delayed erythema after 24 h)

Basis:

other: humans

Remarks:

mean of 8 subjects

Time point:

other: 15 min of tar exposure

Score:

1

Max. score:

4

Reversibility:

fully reversible within: ~30 h

Remarks on result:

other: UVA dose 15 +-2 J/cm2

Remarks:

No individual results documented (Report, Fig.2).

Results 2

Irritation parameter:

erythema score

Remarks:

minimal phototoxic effect (delayed erythema after 24 h)

Basis:

other: humans

Remarks:

mean of 8 subjects

Time point:

other: 30 min of tar exposure

Score:

1

Max. score:

4

Reversibility:

fully reversible within: ~30h

Remarks on result:

other: UVA dose 11.2 +- 3.2 J/cm2

Remarks:

No individual results documented (Report, Fig. 2).

Results 3

Irritation parameter:

erythema score

Remarks:

minimal phototoxic effect (delayed erythema after 24 h)

Basis:

other: humans

Remarks:

mean of 8 subjects

Time point:

other: 60 min of tar exposure

Score:

1

Max. score:

4

Reversibility:

fully reversible within: ~30 h

Remarks on result:

other: UVA dose 5.9 +-1.9 J/cm2

Remarks:

No individual results documented (Report, Fig.2).

Irritant / corrosive response data:

The mean minimal phototoxic UVA-dose (1 h) without tar exposure was relatively variable among the volunteers and estimated to be 22.2 +-6.1 J/cm2. The mean effective erythema UVA dose is higher.
Tar application for 30 min followed by 1h-UV-exposure was photosensitising in all 8 subjects. 6/8 showed photosensitisation already after 15 min.(Report, Fig. 2). Coal-tar induced phototoxicity persisted for about 30 h following a 1h application of tar. Phototoxicity measured as minimal phototoxic effect at increasing exposure times to coal-tar followed a log-log response model (Report Fig. 3), which predicts that further increases in the tar exposure time beyond 3 h is unlikely to produce decreases in the minimal effective UV-dose that may be clinically relevant. After a prolonged tar-exposure interval of 2 h, the mean minimal phototoxic UVA-dose (1 h) approximated about 3 J/cm2 (Fig. 2) as lowest value.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

photo-induced skin irritation

Conclusions:

irritating following exposure to UV light