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Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 weeks, feeding
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
Peer reviewed work as part of US National Toxicity Program on a hydroxy anthraquinone
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
14 week feeding study in male and female rats.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Sex:
male/female
Details on test animals and environmental conditions:
Groups of 10 male and 10 female rats
Route of administration:
oral: feed
Details on oral exposure:
Diets containing 0, 312.5, 625, 1,250, 2,500, or 5,000 ppm emodin
(equivalent to average daily doses of approximately 20, 40, 80, 170, or 300 mg/kg)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
14 weeks
Frequency of treatment:
Daily
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
20 mg/kg bw/day (nominal)
Dose / conc.:
40 mg/kg bw/day (nominal)
Dose / conc.:
80 mg/kg bw/day (nominal)
Dose / conc.:
170 mg/kg bw/day (nominal)
Dose / conc.:
300 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10
Control animals:
yes, plain diet
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean body weights of males exposed to 170 mg/kg/day or greater and females exposed to 80 mg/kg/day or greater were significantly less than those of the controls
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Rerduced food intake at higher treatment levels for the first week
Food efficiency:
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Total serum protein and albumin concentrations were decreased in females exposed to 170 and 300 mg/kg/day.
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Relative kidney weights of rats exposed to 80 mg/kg/day or greater and relative lung weights of rats exposed to 40 mg/kg/day or greater were significantly increased compared to the control groups
Relative liver weights were increased in females exposed to 40 mg/kg/day or greater.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
The incidences of hyaline droplets in the cortical epithelial cytoplasm were increased in all groups of exposed males and in females exposed to higher dose groups
Histopathological findings: neoplastic:
no effects observed
Other effects:
effects observed, treatment-related
Description (incidence and severity):
All male rats exposed to 80 mg/kg/day or greater and all exposed female rats had pigment in the renal tubules; and the severity of pigmentation generally increased with increasing exposure concentration.
Dose descriptor:
NOAEL
Effect level:
ca. 40 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
clinical biochemistry
organ weights and organ / body weight ratios
histopathology: non-neoplastic
Critical effects observed:
yes
Lowest effective dose / conc.:
170 mg/kg bw/day (nominal)
System:
haematopoietic
Organ:
not specified
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified
Critical effects observed:
yes
Lowest effective dose / conc.:
80 mg/kg bw/day (nominal)
System:
urinary
Organ:
kidney
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified

A NOAEL was not described in the report. The changes in the kidney and relative organ weights are considered to be adaptive.

Reduced food intake in higher groups may have been a taste aversion

The blood paramater changes above 80 mg/kg/day were potentially significant and have been used to set the NOAEL. No spcecific target organ was identified.

In other reviews, kidney effects are noted and the effects seen in this study may be significant

Conclusions:
A NOAEL was not described in the report. The changes in the kidney and relative organ weights are considered to be adaptive.
Reduced food intake in higher groups may have been a taste aversion
The blood paramater changes above 80 mg/kg/day were potentially significant and have been used to set the NOAEL. No spcecific target organ was identified.
In other reviews, kidney effects are noted and the effects seen in this study may be significant
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
40 mg/kg bw/day
Study duration:
subchronic
Species:
rat
System:
urinary
Organ:
kidney

Additional information

Justification for classification or non-classification