Pitch, coal tar, high-temp.

Endpoint summary

Description of key information

Pitch, coal tar, high-temp. is considered to be a skin sensitiser, based on a BaP content of 1 - 1.5 %. BaP was shown to be a potent sensitiser in an assay using guinea pigs (Old et al. 1963).

No data is available for respiratory sensitisation. But, there is no evidence of a sensitising potential from occupational experience.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study based on scientific principles, reproducible test method

Qualifier:

no guideline available

Principles of method if other than guideline:

Delayed hypersensitivity/contact sensitisation: Intradermal injection of the agents into the foot pad of guinea pigs for induction in the presence of Freund´s adjuvant, followed by topical/epidermal challenge (method according to: Gell PG and Benacerraf BJ. Exp. Med. 113, 571 (1961)).
Three different PAH were tested: 3-methylcholanthrene (MC), 3,4-benzpyrene (BP), and 9,10-dimethyl-1,2-benzanthracene (DMBA).

GLP compliance:

no

Type of study:

intracutaneous test

Justification for non-LLNA method:

LLNA test method was not available at the time of the study.

Specific details on test material used for the study:

- Name of test material (as cited in study report): 3,4-benzpyrene (BP)
- Analytical purity: "highly purified" (acc. to report)

Species:

guinea pig

Strain:

Hartley

Sex:

female

Route:

other: intradermal into each front food pad

Vehicle:

other: emulsion of complete Freund´s adjuvant with saline

Remarks:

the test substance was dissolved in complete Freund's adjuvant and emulsified with an equal volume of saline

Concentration / amount:

125 µg in 0.1 mL vehicle, total 250 µg; single application

Day(s)/duration:

induction period 2 - 3 wks

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, open

Vehicle:

other: acetone-olive oil mixture (not further specified)

Concentration / amount:

0.001 %

Day(s)/duration:

24 h

Adequacy of challenge:

not specified

No.:

#2

Route:

epicutaneous, open

Vehicle:

other: acetone-olive oil mixture (not further specified)

Concentration / amount:

0.01 %

Day(s)/duration:

24 h

Adequacy of challenge:

not specified

No.:

#3

Route:

epicutaneous, open

Vehicle:

other: acetone-olive oil mixture (not further specified)

Concentration / amount:

0.1 %

Day(s)/duration:

24 h

Adequacy of challenge:

not specified

No.:

#4

Route:

epicutaneous, open

Vehicle:

other: acetone-olive oil mixture (not further specified)

Concentration / amount:

1 %

Day(s)/duration:

24 h

Adequacy of challenge:

not specified

No. of animals per dose:

6, 16, and 10 for MC, BaP, and DMBA, respectively

Details on study design:

RANGE FINDING TESTS: no data

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 (single intradermal application)
- Induction period: 2 - 3 weeks
- Test groups: 4
- Control group: 1
- Site: each front foot pad
- Frequency of applications: 1x
- Concentrations: 250 µg (2 x 125 µg in 0.1 mL vehicle per food pad)
- Auxiliary agent: emulsion in complete Freund´s adjuvant with saline

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (single epicutaneous application)
- Day(s) of challenge: 1
- Exposure period: 24 h
- Test groups: 4
- Control group: 1
- Site: ventral or dorsal shaved skin
- Concentrations: 0.001, 0.01, 0.1,and % (one drop each applied)
- Evaluation (hr after challenge): 24

OTHER:
- Scoring system
according to Gell PG and Benacerraf B J. Exp. Med. 113, 571 (1961): from +++ to 0 (±)

Challenge controls:

PAH known to be contact sensitisers in this test system: MC and DMBA

Positive control substance(s):

yes

Remarks:

MC and DMBA

Positive control results:

MC +++ (≥ 0.1 %); DMBA +++ (1 %).
Dose-related intensity of the responses

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.001%

Clinical observations:

contact reactivity with score +

Remarks on result:

positive indication of skin sensitisation

Remarks:

score + indicates the onset of a sensitising effect

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.01%

Clinical observations:

contact reactivity with score ++

Remarks on result:

positive indication of skin sensitisation

Remarks:

score ++ shows a moderate sensitising response

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1%

Clinical observations:

contact reactivity with score +++

Remarks on result:

positive indication of skin sensitisation

Remarks:

score +++ demonstrates a clear sensitising response

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1 %

Clinical observations:

contact reactivity with score +++

Remarks on result:

positive indication of skin sensitisation

Remarks:

score +++ demonstrates a clear sensitising response

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.001 - 1 %

No. with + reactions:

0

Total no. in group:

4

Clinical observations:

reponse - to ± (negative to slight erythema)

Remarks on result:

no indication of skin sensitisation

Remarks:

negative response on challenge

There was a dose-related increase in the intensity of the delayed contact reactivity. There was also cross-reactivity with MC and DMBA as challenging agent and BaP with previous inducer. The intensity of the response was dose-related but primarily expressed at the higher challenge doses, i.e. weaker than with BaP as challenger.

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Remarks:

dose related intensity of the response with regard to the test substance concentration during challenge

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The source substance benzo[a]pyrene (BaP) is one of the most relevant components of the target substance pitch, coal tar, high-temp. (CTPht). During processing and use of CTPht, BaP may be released into the environment and can be taken up by humans or other living organisms. There the substance can exert adverse toxicological effects.
BaP is the most abundant and with regard to toxicological effects one of the most relevant constituent of CTPht. It is considered to adequately characterise the toxicological effects of CTPht as a whole. Therefore, BaP as source substance can be used as supporting substance. Data resulting from the source substance are considered valid for characterising the toxicological properties of the target substance CTPht.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source test material is benzo[a]pyrene. Analytical purity is not specified, but reported as highly purified. Purity of the substance is considered to be high enough that study results are related to effects caused by BaP.
The target material pitch, coal tar, high-temp. is a UVCB substance. It is the product (residue) of the oxygen free high-temperature distillation of tar, coal, high-temperature (CAS No. 65996-89-6) and consists of a complex mixture of polycyclic aromatic hydrocarbons, predominantly of highly condensed to some extent carbonised aromatic ring systems forming an inert matrix. This matrix is not accessible by common analytical tools. In this matrix, individual PAH with a lower degree of condensation are included. This is demonstrated by the fact that only a fraction of ca. 20 % of the substance will evaporate at a distillation temperature up to 500 °C. The GC-analysable fraction comprises polycyclic aromatic hydrocarbons predominantly with four and five (up to six) condensed ring systems. Fraction of the 16 EPA PAH in GC analysis is up to 7.5 % with up to 1.5 % of them being BaP. Water solubility is very low (ca. 0.24 mg dissolved C/L at a loading of 1000 mg substance/L or 1.3 µg/L sum of EPA PAH at a loading of 100 mg substance /L).

3. ANALOGUE APPROACH JUSTIFICATION
Under environmental conditions or during processing of the substance, environmentally available or volatile components of CTPht may be released. These will be PAH (mainly four and five ring representatives) incorporated into the inert matrix. The most relevant PAH among them under a toxicological point of view is benzo[a]pyrene. This substance is besides benzo[b]fluoranthene the most abundant PAH, determined under the components of CTPht analysable by GC. Toxicity of BaP is comparable to or even higher than the toxicity of the other PAH present in CTPht and thus constitutes the toxicity of CTPht as a whole. As release of PAH from CTPht is very limited, using toxicity data of BaP for CTPht will very likely overestimate risk arising from CTPht.
For these reasons, BaP is selected as marker substance for the toxic effects of the substance CTPht itself. Data determined for BaP will be taken to characterise CTPht in its entirety and will be used in the chemical safety assessment of CTPht. Thus, it is justified to use data arising from the supporting substance BaP as surrogate for read-across to the target substance CTPht.

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Read-across to the preceding entry:
Source substance: benzo[a]pyrene (benzo[def]chrysene), generic (commercial product);
Reference: Old LJ et al. 1993; WHO 1998; ATSDR 1995

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.001 %

Clinical observations:

contact reactivity with score +

Remarks on result:

positive indication of skin sensitisation

Remarks:

score + indicates the onset of a sensitising effect / test result is adopted for the target substance CTPht

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.01 %

Clinical observations:

contact reactivity with score ++

Remarks on result:

positive indication of skin sensitisation

Remarks:

score ++ shows a moderate sensitising response / test result is adopted for the target substance CTPht

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 %

Clinical observations:

contact reactivity with score +++

Remarks on result:

positive indication of skin sensitisation

Remarks:

score +++ demonstrates a clear sensitising response / test result is adopted for the target substance CTPht

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1 %

Clinical observations:

contact reactivity with score +++

Remarks on result:

positive indication of skin sensitisation

Remarks:

test result is adopted for the target substance CTPht

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

No data is available on sensitising effects of CTPht itself. BaP is used as supporting substance to characterise the sensitising potential of CTPht. This is justified as BaP is a constituent of CTPht at a concentration high enough to cause relevant effects with regard to a sensitive toxicological endpoint such as sensitisation.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin Sensitisation

Based on a content of up to 1.5% of benzo[a]pyrene, a strong sensitiser, pitch, coal tar, high-temp., is classified as sensitising Cat. 1 by the registrant.

Respiratory Sensitisation

No experimental data is available on respiratory sensitisation. However, based on long-term occupational experience, no classification required.