1,4-dihydroxyanthraquinone

Endpoint summary

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

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study 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 or test system 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

histopathology: non-neoplastic

organ weights and organ / body weight ratios

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