Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
no guideline available
Version / remarks:
The experiment has been cited, discussed and referred to as evidence for low toxicity in Chappel et al. (1998) Food Chem. Toxicol. volume 36, pp. 915-922 and in Gerhauser C (2005) Eur. J. Cancer vol. 41, pp. 1941-1954.
Principles of method if other than guideline:
90-day subactue toxicity feeding study set up using 1, 0.1 and 0.01% of hop iso-alpha acids in corn oil, plus a negative control, fed to 21-day-old Sprague-Dawley rats.
GLP compliance:
not specified
Specific details on test material used for the study:
Isomerized hop extract present as a 50% suspension in corn oil. This will be an extract enriched in hop iso-alpha acids.
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on oral exposure:
Rats provided with test ration and water ad libitum.
Duration of treatment / exposure:
90 days
Dose / conc.:
0 ppm
Remarks:
Iso-alpha acids present at 0, 0.01, 0.1 and 1% in the study design
Dose / conc.:
100 ppm
Remarks:
Iso-alpha acids present at 0, 0.01, 0.1 and 1% in the study design
Dose / conc.:
1 000 ppm
Remarks:
Iso-alpha acids present at 0, 0.01, 0.1 and 1% in the study design
Dose / conc.:
10 000 ppm
Remarks:
Iso-alpha acids present at 0, 0.01, 0.1 and 1% in the study design
No. of animals per sex per dose:
10
Observations and examinations performed and frequency:
Animals weighed and their food consumption measured weekly. Periodic check for abnormal blood elements and urine elements made on high level groups and control.
Sacrifice and pathology:
Certain organs weighed (body, liver, heart, spleen, kidneys, gonads); certain organs examined microscopically (heart, lung, spleen, liver, pancreas, stomach and intestine, mesenteric lymph nodes, salivary glands, thyroid, kidney, urinary bladder, ovary or testis, uterus or prostate, bone and bone marrow)
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Reduced weight gain at the highest level (1%), but no changes in weights of liver, heart, spleen, kidneys or gonads, and no histopathological changes. The reduced weight gain is likely to be due to the unpalatibility of teh bitter iso-alpha acids.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Reduced weight gain at the highest level (1%), but no changes in weights of liver, heart, spleen, kidneys or gonads, and no histopathological changes. The reduced weight gain is likely to be due to the unpalatibility of teh bitter iso-alpha acids
Key result
Dose descriptor:
dose level: Highest dose rate (1%) led to reduced weight gains; no changes observed in weights of liver, heart, spleen, kidneys or gonads were noted, and no histopathological changes noted.
Effect level:
ca. 10 000 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Key result
Critical effects observed:
no
Conclusions:
Discussion in JI Haas proprietary documents for GRAS approval of iso-alpha acids:highest dose rate (1%) led to reduced weight gains; no changes observed in weights of liver, heart, spleen, kidneys or gonads were noted, and no histopathological changes noted. If the reduced weight gain is seen as toxicologically significant, then NOAEL would be equivalent to 50-75 mg per kg bw per day, but if the weight loss was due to the unpalatability of the bitter iso-alpha acids, NOAEL would be 500 - 750 mg per kg bw per day.
Endpoint:
sub-chronic toxicity: oral
Type of information:
other: Summary of weight of evidence for hop extract components
Adequacy of study:
other information
Justification for type of information:
See the attached background material. Company Report BI/YYF/REACH/2018 -006 gives a comprehensive summary of the existing data relating to hop extract toxicity and why further animal studies are not warranted. This document shows that hop extracts and their derivatives have already been assessed as safe for1. food (US FDA),2. medicinal use (EMEA assessment), and3. cosmetic use (Cosmetic Ingredient Review Panel). The other 5 documents are attached for ease of reference since they are cited in BI/YYF/REACH/2018 -006 and provide further relevant information.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Justification for classification or non-classification

Discussion in JI Haas proprietary documents for GRAS approval of iso-alpha acids:highest dose rate (1%) led to reduced weight gains; no changes observed in weights of liver, heart, spleen, kidneys or gonads were noted, and no histopathological changes noted. If the reduced weight gain is seen as toxicologically significant, then NOAEL would be equivalent to 50-75 mg per kg bw per day, but if the weight loss was due to the unpalatability of the bitter iso-alpha acids, NOAEL would be 500 - 750 mg per kg bw per day.