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Effects on fertility

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Reference
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
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
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 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
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)
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.
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: 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
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.
Key result
Reproductive effects observed:
not specified
Lowest effective dose / conc.:
10 000 ppm
Treatment related:
yes
Conclusions:
See the attached background material that gives an analysis of existing data. Further animal studies are not warranted.
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed

Justification for classification or non-classification

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