α-Bitter acids, hop, hydrogenated, isomerized

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Well-documented study from 1995, performed to GLP. This supporting study was performed on a major derivative of hop iso-alpha acids, of very similar structure to hop tetrahydroiso-alpha acids.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Principles of method if other than guideline:

The test article, RHO isoalpha acids; 89.4% concentration, was tested in the CHO/HGPRT Mutation Assay in two phases.

GLP compliance:

yes

Type of assay:

in vitro mammalian cell micronucleus test

Specific details on test material used for the study:

Lot no. 1463-F; purity 89.4%; described as thick golden brown, very viscous liquid

Target gene:

HGPRT

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9

Test concentrations with justification for top dose:

0.5 - 5000 ug per ml.

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

ethylmethanesulphonate

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Conclusions:

Test report shows that all criteria for a valid study were met. The results indicated that the substance did not cause a positive response in the non-activated and activated systems, and was concluded to be negative.
Study performed on major derivative of hop iso-alpha acids.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Well-documented study from 1991, performed to GLP. This supporting study was performed on hop iso-alpha acids, or very similar structure to hop tetrahydroiso-alpha acids.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

The test article, 40% isohumulones (i.e. hop iso-alpha-acids);40% concentration, was tested in the Salmonella Mutagenicity Assay using tester strains TA98, TA100, TA1535, TA1537 and TA1538 in the presence and absence of Aroclor-induced rat liver microsomal enzymes. Three phases, using the plate incorporation method: 1st: a dose range-finding study; 2nd and 3rd: mutagenicity and confirmatory assays.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine mutations hisG46, hisC3076 and hisD3052, and additional mutations: rfa, uvrB

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Test concentrations with justification for top dose:

The maximum dose tested in the dose range-finding study was 100 ug per plate. No precipitate and no appreciable toxicity were observed. The maximum dose in the mutagenicity assay was increased to 1000 ug per plate. No appreciable toxicity was observed at 1000 ug per plate, so the dose was increased to 10,000 ug per plate in the confirmatory assay.

Vehicle / solvent:

Ethanol

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

2-nitrofluorene

sodium azide

other: 2-aminoanthracene, ICR-191

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

No apreciable toxicity observed at 1000 ug per plate. Increased to 10,000 ug per plate in confirmtaory assay to demonstrate reduction in bacterial lawn.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Conclusions:

Test report shows that all criteria for a valid study were met. The results indicated that the substance did not cause a positive response in any of the tester strains in the presence and absence of microsomal enzymes prepared from Aroclor-induced liver.

Reference 3

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Well-documented study from 1995, performed to GLP. This supporting study was performed on hop hexahydroiso-alpha acids, of very similar structure to hop tetrahydroiso-alpha acids.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Principles of method if other than guideline:

The test article, Hexahydro-isoalpha acids; 97.7% concentration, was tested in the CHO/HGPRT Mutation Assay in two phases.

GLP compliance:

yes

Type of assay:

in vitro mammalian cell micronucleus test

Specific details on test material used for the study:

Lot no. 1023-F; purity 97.7%; described as a brown solid

Target gene:

HGPRT

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254-induced rat liver S9

Test concentrations with justification for top dose:

800 ug per ml.

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

ethylmethanesulphonate

Key result

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Conclusions:

Test report shows that all criteria for a valid study were met. The results indicated that the substance did not cause a positive response in the non-activated and activated systems, and was concluded to be negative.
Study performed on major derivative of hop iso-alpha acids, very similar in structure to tetrahydroiso-alpha acids.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)