Hop, Humulus lupulus, ext.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

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:

according 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:

Hop, Humulus lupulus, ext.

EC Number:

232-504-3

EC Name:

Hop, Humulus lupulus, ext.

Cas Number:

8060-28-4

Molecular formula:

No simple molecular formula for UVCB

IUPAC Name:

Hop, Humulus lupulus, ext.

Test material form:

liquid: viscous

Remarks:

Depending on the extraction conditions and on the hop variety, the colour of the extract can vary from yellow to dark green. It is a semi-fluid paste at room temperature. The product becomes more fluid when heated.

Test animals

Species:

mouse

Details on test animals or test system and environmental conditions:

Rat and mouse data cited in Handbook

Results and discussion

Effect levels

Key result

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: 1,000 - 2,300 mg/kg bw for beta-acid-enriched hop extract

Applicant's summary and conclusion

Conclusions:

Hop extracts are widely used as ingredients for beer. They are generally regarded as safe (GRAS) according to USA law 21 CFR 182.20. Within the European Union, an assessment report of Humulus lupulus by the European Medicines Agency (EMEA) in 2014 is available on the web. Section 3.3 of that report states: “Hops have been used in the brewing industry for centuries without any known adverse effect to the health of consumers. Thus, given the history of long-term and present use in humans with no significant adverse effects, it is considered that hops are safe (Chadwick et al., 2006).” LD50 values are quoted in Section 3.3.1 of that report as follows:

• Ethanolic hop extract: LD50 3,500 mg/kg/b.w. p.o., 1,200 mg/kg/b.w. s.c. (mice); LD50 2,700 mg/kg/b.w. p.o. (rats).
• Methylisobutylketone-hop extract: LD50 2,700 mg/kg/b.w. p.o. (mice); LD50 415 mg/kg/b.w. p.o. (rats).

This suggests an expected LD50 for oral administration >2,000 mg per kg bw for most hop extracts, i.e. not triggering a hazard classification under Regulation (EC) 1272/2008.

2. β-ACID-ENRICHED HOP EXTRACT

An LD50 of ca. 700 mg per kg bw was estimated for β-acids (see attached report Hop Extract_Data Summary.pdf). Thus a β-acid-enriched hop extract, containing 30 – 70% β-acids, could potentially have an LD50 value of 1,000 – 2,300 mg per kg bw. This would potentially place certain extracts (>35% β-acids) under Category 4 for Acute Toxicity according to Regulation (EC) 1272/2008, section 3.1.2.1, with the Signal Word “Warning”, and the Hazard Statement “H302: Harmful if swallowed”.