Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
Qualifier:
equivalent or similar to
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
Species:
other: rat data cited in GRAS assessment
Key result
Dose descriptor:
LD50
Effect level:
ca. 1 000 mg/kg bw
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"
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 000 mg/kg bw

Additional information

Justification for classification or non-classification