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Administrative data

Endpoint:
reproductive toxicity, other
Remarks:
See experimental details and the weight of evidence data in the background material.
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
90 days
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation

Data source

Referenceopen allclose all

Reference Type:
other company data
Title:
Unnamed
Year:
2008
Report date:
2008
Reference Type:
study report
Title:
Unnamed
Year:
1960
Report date:
1960

Materials and methods

Test guideline
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. Histopathological examinations of tissues including reproductive tissues.
GLP compliance:
not specified

Test material

1
Chemical structure
Reference substance name:
3,4-dihydroxy-5-(3-methylbut-2-enyl)-2-(3-methyl-1-oxobutyl)-4-(4-methyl-1-oxopent-3-enyl)cyclopent-2-en-1-one
EC Number:
247-072-1
EC Name:
3,4-dihydroxy-5-(3-methylbut-2-enyl)-2-(3-methyl-1-oxobutyl)-4-(4-methyl-1-oxopent-3-enyl)cyclopent-2-en-1-one
Cas Number:
25522-96-7
Molecular formula:
C21H30O5
IUPAC Name:
3,4-Dihydroxy-5-(3-methylbut-2-enyl)-2-(3-methyl-1-oxobutyl)-4-(4-methyl-1-oxopent-3-enyl)cyclopent-2-en-1-one
2
Chemical structure
Reference substance name:
3,4-dihydroxy-5-(3-methylbut-2-enyl)-4-(4-methyl-1-oxopent-3-enyl)-2-(2-methyl-1-oxopropyl)cyclopent-2-en-1-one
EC Number:
246-780-8
EC Name:
3,4-dihydroxy-5-(3-methylbut-2-enyl)-4-(4-methyl-1-oxopent-3-enyl)-2-(2-methyl-1-oxopropyl)cyclopent-2-en-1-one
Cas Number:
25269-20-9
Molecular formula:
C20H28O5
IUPAC Name:
3,4-dihydroxy-5-(3-methylbut-2-enyl)-4-(4-methyl-1-oxopent-3-enyl)-2-(2-methyl-1-oxopropyl)cyclopent-2-en-1-one
3
Chemical structure
Reference substance name:
3,4-dihydroxy-5-(3-methylbut-2-enyl)-2-(2-methyl-1-oxobutyl)-4-(4-methyl-1-oxopent-3-enyl)cyclopent-2-en-1-one
EC Number:
246-967-4
EC Name:
3,4-dihydroxy-5-(3-methylbut-2-enyl)-2-(2-methyl-1-oxobutyl)-4-(4-methyl-1-oxopent-3-enyl)cyclopent-2-en-1-one
Cas Number:
25422-83-7
Molecular formula:
C21H30O5
IUPAC Name:
3,4-dihydroxy-5-(3-methylbut-2-enyl)-2-(2-methyl-1-oxobutyl)-4-(4-methyl-1-oxopent-3-enyl)cyclopent-2-en-1-one
Test material form:
liquid
Details on test material:
Isomerized hop extract present as 50% suspension in corn oil
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.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
corn oil
Details on exposure:
Rats provided with test ration and water ad libitum
Duration of treatment / exposure:
90 days
Doses / concentrationsopen allclose all
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

Examinations

Parental animals: Observations and examinations:
Animals weighed and their food consumption measured weekly. Periodic check for abnormal blood elements and urine elements made on high level groups and control.
Postmortem examinations (parental animals):
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)

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

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.

Details on results (P0)

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.

Effect levels (P0)

Key result
Dose descriptor:
dose level: NOAEL can be estimated from effects at highest dose level
Effect level:
ca. 10 000 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
body weight and weight gain

Results: F1 generation

Effect levels (F1)

Key result
Dose descriptor:
other: F1 offspring not tested in this experiment
Remarks:
Histopathological examination of reproductive tissues in parents only
Generation:
other: F1 offspring not tested in this experiment
Effect level:
0 other: Histopathological examination of reproductive tissues in parents only
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: F1 offspring not tested in this experiment
Remarks on result:
other: See the attached background material that gives an analysis of existing data. Further animal studies are not warranted.

Overall reproductive toxicity

Key result
Reproductive effects observed:
not specified
Lowest effective dose / conc.:
10 000 ppm
Treatment related:
yes

Applicant's summary and conclusion

Conclusions:
See the attached background material that gives an analysis of existing data. Further animal studies are not warranted.

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