3,5-dihydroxy-2,6,6-tris(3-methylbuten-2-yl)-4-(3-methyl-1-oxobutyl)cyclohexa-2,4-dien-1-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

other: Published LD50 values for lupulone are reported in the US Library of Medicine Toxnet ChemIDplus entry for lupulone; discussed in EMEA assessment report that cites Hagers Handbuch

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:

secondary source

Title:

Unnamed

Year:

2014

Report date:

2014

Reference 3

Reference Type:

review article or handbook

Title:

Hagers Handbuch der Pharmazeutischen Praxis. Drogen E—O. Chapter H

Author:

F. von Bruchhausen, G. Dannhardt, S. Ebel, A. W. Frahm, E. Hackenthal, R. Hänsel et al.

Year:

1993

Bibliographic source:

https://doi.org/10.1007/978-3-642-57993-6

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Data obtained from Handbook, and cited in EMEA assessment of hop extracts

GLP compliance:

not specified

Test type:

other: Data obtained from Handbook, and cited in EMEA assessment of hop extracts

Test material

Test material information

Constituent 1

Reference substance name:

3,5-dihydroxy-2,6,6-tris(3-methylbuten-2-yl)-4-(3-methyl-1-oxobutyl)cyclohexa-2,4-dien-1-one

EC Number:

207-405-3

EC Name:

3,5-dihydroxy-2,6,6-tris(3-methylbuten-2-yl)-4-(3-methyl-1-oxobutyl)cyclohexa-2,4-dien-1-one

Cas Number:

468-28-0

Molecular formula:

C26-H38-O4

IUPAC Name:

Lupulone

Test animals

Species:

other: rat and mouse data cited in EMEA assessment and in Handbook

Results and discussion

Effect levels

Key result

Dose descriptor:

LD50

Effect level:

> 100 - <= 1 800 mg/kg bw

Remarks on result:

other: LD50 of 700 mg per kg bw is reasonable based on available data and related compounds

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

An assessment report of Humulus lupulus by the European Medicines Agency (EMEA) in 2014 is available on the web. This report also quotes LD50 values for lupulone of 525 mg/kg/bw p.o., 1,200 mg/kg/bw s.c., and 600 mg/kg/bw s.c. for mice. The EMEA report quotes further LD50 values for lupulone of 1,800 mg/kg/bw p.o. and 330 mg/kg/bw i.m. for rats. Similar LD50 values for humulone (one of the hop α-acids, with a closely-related structure to the β-acids) are also quoted: 1,500 mg/kg/bw p.o. and 600 mg/kg/bw i.m. for rats.

Since LD50 values for β-acids have been quoted in the scientific literature, further animal studies are not warranted.

The LD50 values for oral administration of lupulone range from 100 – 1,800 mg per kg bw, with a mean value of 711 mg per kg bw. A read-across value of 1,500 mg per kg bw for the closely-related humulone adds weight to this being the appropriate order of toxicity. An LD50 of ca. 700 mg/kg for β-acids triggers a classification of Category 4 for Acute Toxicity according to Regulation (EC) 1272/2008, section 3.1.2.1, with the Signal Word “Warning”, the Hazard Statement “H302: Harmful if swallowed” (Regulation (EC) 1272/2008, section 3.1.4).