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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Pitch, coal tar, high-temp., < 1% 4- to 5-membered condensed ring aromatic hydrocarbons [EC no. 701-305-8] (CTPhtht) showed a positive response in a bacterial reverse mutation assay (Ames test). Furthermore, the substance is classified as mutagenic Cat. 1B due to its benzo[a]pyrene content of up to 0.10 %.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 Jul. - 03 Sep. 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Principles of method if other than guideline:
Plate incorporation test
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Additional strain / cell type characteristics:
other:
Remarks:
see report, p. 15 for details
Metabolic activation:
with and without
Metabolic activation system:
S9 microsomal fraction was prepared from induced livers of male Wistar rats, induced with phenobarbital (80 mg/kg bw) and ß-naphthoflavone (100 mg/kg bw) orally (3x)
Test concentrations with justification for top dose:
Pre-experiment: 3.16, 10, 31.6, 100, 316, 1000, 2500, and 5000 µg/plate (TA 98, TA 100: +/-S9)
1st experiment: 31.6, 100, 316, 1000, 2500, and 5000 µg/plate (all tester strains, +/-S9)
2nd experiment: 250, 500, 1000, 2000, 2500, and 5000 µg/plate (all tester strains except TA 1537, +/-S9),
in addition: 125 µg/plate only for TA 98, +S9,
20, 80, 200, 800, 2000, and 5000 µg/plate (TA 1537, +S9),
250, 500, 1000, 2000, 3500, and 5000 µg/plate (TA 1537, -S9)
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Test item was suspended in ethanol and diluted prior to use.
- Justification for choice of solvent/vehicle: compatible with survival of bacteria and S9 activity
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: Sodium azide, 4-nitro-o-phenylene-diamine (4-NOPD), methyl methane sulphonate (MMS), 2-aminoanthracene (2-AA); see Report p. 15 for details
Details on test system and experimental conditions:
METHOD OF APPLICATION:
in agar (plate incorporation): Materials were mixed in test tube and poured over the surface of a minimal agar plate
- Test solution (at each dose level, solvent control, negative control, or positive control: 100 µl
- S9 mix (for testing with metabolic activation or S9 mix substitution buffer (for testing without metabolic activation): 500 µl
- Bacteria suspension: 100 µl
- Overlaying agar: 2000 µl

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth/colony formation

Evaluation criteria:
Considered as mutagenic
- if a clear and dose-related increase in the number of revertants occurs in at least one tester with or without metabolic activation
and/or
- if a biologically relevant positive response for at least one of the dose groups occurs in at least one tester with or without metabolic activation.

An increase is considered relevant
- if in TA 100 and TA 102 mutation rate is at least twice as high as the rate of the solvent control;
- if in TA 98, TA 1535, and TA 1537 the mutation rate is at least 3x higher than that of the solvent control.


Statistics:
According to the OECD guidelines, the biological relevance is the criterion for the interpretation of the results: a statistical evaluation was not considered necessary under this premise (report p. 21).
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
positive
Remarks:
reproducible, dose-response relationship in both experiments with metabolic activation. Without S9, weakly positive in one test.
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with
Genotoxicity:
positive
Remarks:
reproducible
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with
Genotoxicity:
positive
Remarks:
reproducible, dose-response relationship
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: in all tester strains at test concentrations of >= 1000 µg/plate (1st experiment);
in all tester strains except tester strain TA 1537 at test concentrations of >= 1000 µg/plate (2nd experiment)
in tester strain TA 1537 at a test concentration of >= 1000 µg/plate (2nd experiment, without metabolic activation) and
at a test concentration of >= 800 µg/plate (2nd experiment, with metabolic activation)


Maximum mutation factor: 14.3 (tester strain TA 98 with metabolic activation at a dose of 3500 µg/plate, 1st experiment)

Conclusions:
Interpretation of results:
positive
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Additional information

Additional information from genetic toxicity in vitro:

Mutagenicity of Pitch, coal tar, high-temp., < 1% 4- to 5-membered condensed ring aromatic hydrocarbons [EC no. 701-305-8] (CTPhtht) was tested in a bacterial reverse mutation assay (Ames test) according to OECD TG 471/EU Method B.13/14. CTPhtht proved to be positive in three of five tester strains. Additional cytotoxicity/mutagenicity tests were not conducted, as CTPhtht has been self-classified as mutagenic (Muta. 1B) and carcinogenic (Carc 1B) due to its content of benzo[a]pyrene (≥ 0.1 %), which itself is classified as carcinogenic and mutagenic (Carc. 1B, Muta.1B).

Justification for classification or non-classification

Pitch, coal tar, high-temp., < 1% 4- to 5-membered condensed ring aromatic hydrocarbons [EC no. 701-305-8] (CTPhtht) may contain up to 0.10 % of benzo[a]pyrene (BaP). BaP is known to be mutagenic and is classified as mutagenic Cat. 1B. In an Ames test, CTPhtht was demonstrated to be mutagenic. Based on BaP content, CTPhtht has been classified as mutagenic Cat. 1B by the registrant.