Extract of fava d'anta, obtained from the fruits of Dimorphandra mollis (Leguminosae) by solvent extraction

Toxicity to reproduction

Administrative data

Endpoint:

reproductive toxicity, other

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1947

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Data source

Reference

Reference Type:

publication

Title:

Toxicity Studies on Rutin

Author:

Wilson RH

Year:

1947

Bibliographic source:

Proceedings of the Society for Experimental Biology and Medicine, 1947 64 : 3 , 324-327

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A reproductive toxicity test was conducted for the test item in Albino rats. After 150 days of treatment with 1% test item in diet, 6 males and 6 females, were mated after being caged together for a month

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Rutoside

EC Number:

205-814-1

EC Name:

Rutoside

Cas Number:

153-18-4

Molecular formula:

C27H30O16

IUPAC Name:

2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl 6-O-(6-deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranoside

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

other: Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: about 90 g

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
1.0% (w/w) of the test item was thoroughly mixed into finely ground Purina Dog Chow.

Details on mating procedure:

- M/F ratio per cage:1:1
- Length of cohabitation: 1 month

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

400 days

Frequency of treatment:

daily

Details on study schedule:

After 150 days of treatment, the 6 males and 6 females on the 1 % test item diet were caged together for a month and mated. Afterwards, they were observed periodically until they had been eating the diet for 400 days.

Doses / concentrations

Dose / conc.:

1 other: % in diet

No. of animals per sex per dose:

6 males and 6 females

Control animals:

yes, plain diet

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Cage side observations checked: mortality

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: Daily

FOOD CONSUMPTION AND COMPOUND INTAKE: No
WATER CONSUMPTION AND COMPOUND INTAKE: No

Oestrous cyclicity (parental animals):

The length of the estrous cycle was measured

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
Number of pups, stillbirths, live births, postnatal mortality.

GROSS EXAMINATION OF DEAD PUPS: No
ASSESSMENT OF DEVELOPMENTAL NEUROTOXICITY: No
ASSESSMENT OF DEVELOPMENTAL IMMUNOTOXICITY: No

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals
- Maternal animals: All surviving animals

GROSS NECROPSY
- Gross necropsy consisted of unspecified tissues

HISTOPATHOLOGY / ORGAN WEIGHTS
Tissues from all of the animals (both the 150-day and 400-day rats) were embedded in paraffin and sections were stained with hematoxylin and eosin. Histopathological study of these sections was made by Dr. A. J. Cox, Jr., Stanford University School of Medicine, San Francisco.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Endocrine findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

The animals which received 1% test item in the diet for 400 days showed slight irregularity in vacuolation of the cortical cells of the adrenals, which may signify a little irregularity in lipoid content
of the cells. However, this was not pronounced and is of doubtful significance. In 3 of the 6 female rats which received the 1% test item diet there was distinctly more brown granular pigment in the renal epithelial cells than in the controls. However, since all of the control animals were males, this observation cannot be interpreted. The male rats receiving the same amount of test item did not show this change.

Histopathological findings: neoplastic:

not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Details on results (P0)

From the unions, there resulted 4 litters from 3 of the females.

Effect levels (P0)

Key result

Dose descriptor:

NOAEL

Effect level:

1 other: % in diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

Remarks on result:

other: Equivalent to 500 mg/kg bw

Target system / organ toxicity (P0)

Key result

Critical effects observed:

no

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality / viability:

mortality observed, non-treatment-related

Description (incidence and severity):

One of the 4 litters was born dead

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

3 liiters were small (3 to 5 per litter)

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

not examined

Anogenital distance (AGD):

not examined

Nipple retention in male pups:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

not examined

Histopathological findings:

not examined

Other effects:

not examined

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not examined

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 other: % diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no significant effects observed

Remarks on result:

other: 500 mg/kg bw day

Target system / organ toxicity (F1)

Key result

Critical effects observed:

no

Overall reproductive toxicity

Key result

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

The reproductive toxicity assay of the test item in Albino rats has a NOAEL of 1% in diet for both sexes (500 mg/kg bw day).

Executive summary:

A reproductive toxicity test was conducted for the test item in Albino rats. After 150 days of treatment with 1% test item in diet, 6 males and 6 females, were mated after being caged together for a month. 4 litters from 3 of the females were born and one of them was born dead and the other 3 were small (3 to 5 per litter). As no relevant effects were observed at the highest dose tested, the test item has a NOAEL of 1 % in diet in Albino rats for both sexes (500 mg/kg bw, conversion according to the guidelines for the preparation of working papers for the joint FAO/WHO expert committee on food additives).