α-Bitter acids, hop, hydrogenated, isomerized

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

other: Published LD50 values for iso-alpha acids and rho-iso-alpha acids are cited in a company report and in a recent scientific publication.

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Data source

Reference

Reference 1

Reference Type:

other company data

Title:

Unnamed

Year:

2017

Report date:

2017

Reference 2

Reference Type:

other company data

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Data obtained from closely related molecules, on which from GRAS assessment

GLP compliance:

not specified

Test type:

other: Data obtained from GRAS assessment

Test material

Test material information

Constituent 1

Reference substance name:

3,4-dihydroxy-5-(3-methylbut-2-enyl)-2-(3-methyl-1-oxobutyl)-4-(4-methyl-1-oxopent-3-enyl)cyclopent-2-en-1-one

EC Number:

247-072-1

EC Name:

3,4-dihydroxy-5-(3-methylbut-2-enyl)-2-(3-methyl-1-oxobutyl)-4-(4-methyl-1-oxopent-3-enyl)cyclopent-2-en-1-one

Cas Number:

25522-96-7

Molecular formula:

C21H30O5

Test animals

Species:

other: rat data cited in GRAS assessment

Results and discussion

Effect levels

Key result

Dose descriptor:

LD50

Effect level:

ca. 1 000 mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Notes from attached justification: "Safety assessments of tetrahydroiso-α-acids were discussed in detail in company report BI/YYF/REACH/2007-001.1 In summary:

• The reduced derivatives are approved food additives for beer in the USA, under 21 CFR § 172.560.6 Safety assessments of these compounds have been performed.
• BI/YYF/REACH/2007-0011 provides discussions of acute dermal toxicity, acute inhalation toxicity, sub-acute toxicity studies, animal and human studies, mutagenicity and genotoxicity studies on iso-α-acids, rho-iso-α-acids, and tetrahydroiso-α-acids, which can be considered together using a read-across approach.
• The acute toxicity of tetrahydroiso-α-acids can be read across from LD50 values of 1,000 mg per kg for iso-α-acids and rho-iso-α-acids: see BI/YYF/REACH/2007-0011 and Karabin et al. (2016).

Since LD50 values for the closely-related iso-α-acids and rho-iso-α-acids have been quoted in the scientific literature, further animal studies are not warranted."

In addition: "Interestingly, the potassium salt of tetrahydroisohumulone has been tested as a potential drug for improving metabolism in prediabetic humans in a clinical research centre. .... Key points taken from the safety assessment detailed in the article are as follows:

• No cases of stopping the drug or of altering the dose
• All adverse effects were mild or moderate, and all resolved spontaneously
• The adverse effects were mostly gastrointestinal effects
• No evidence of greater toxicity with higher serum levels of KDT501
• No significant findings in clinical laboratory evaluations
• No evidence of liver, kidney or bone marrow toxicity"