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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:
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
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
Species:
mouse
Details on test animals or test system and environmental conditions:
Rat and mouse data cited in Handbook
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
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”.
Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

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.

Further animal studies are not warranted for either the acute dermal toxicity or the acute inhalation toxicity end-points:

1. Hop extract is a UVCB with principal components being hop bitter acids (α- and β-acids) and hop essential oil.

2. Oral LD50 values have been published for hop extract and for hop bitter acids.

3. The weight of evidence does not suggest that the acute dermal toxicity of hop extract would be significantly higher than the acute oral toxicity. Reported values for dermal toxicity show that the LD50 of a hop extract injected under the skin of mice was of the same order of magnitude as that for oral administration.

4. The Cosmetic Ingredient Review Expert Panel and the European Flavour and Fragrances Association (EFFA) did not classify hop extract or hop oils with dermal toxicity.

5. The α- and β-acids are not volatile. The volatile component of hop extract is the essential oil.

6. The volatile hop oils have not been classified as toxic by inhalation.

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