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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Remarks:
based on test type
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Studies on the reproductive, cytological and biochemical toxicity of Ginkgo Biloba in Swiss albino mice
Author:
Abdulaziz A. Al-Yahya, Abdulhakeem A. Al-Majed ∗, A.M. Al-Bekairi, O.A. Al-Shabanah, S. Qureshi
Year:
2006
Bibliographic source:
Journal of Ethnopharmacology 107 (2006) 222–228

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Effect of Ginkgo Biloba on reproductive parameters in Swiss albino mice.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source:Experimental Animal Care Center- Age at study initiation:6–8 weeks- Weight at study initiation: 25–28 g- Fasting period before study:Not available- Housing:Details not available- Diet (e.g. ad libitum):Purina chowdiet ad libitum- Water (e.g. ad libitum):ad libitum- Acclimation period:Not availableENVIRONMENTAL CONDITIONS- Temperature (°C):Standard conditions- Humidity (%):Standard conditions- Photoperiod (hrs dark / hrs light):12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:Aqueous suspension of Ginkgo biloba was administered by gastric intubation (oral) daily for a period of 90 days.
Details on mating procedure:
- M/F ratio per cage:1:3- Length of cohabitation:1 week- Proof of pregnancy:Not available- After successful mating each pregnant female was caged (how):individually- Any other deviations from standard protocol:each male mouse in the treated and control groups was caged with three females, which were allowed to stay with the male for 1 week. The female mice were necropsied 13 days following the mid-week of their caging and presumptive mating and the number of pregnant mice was recorded to determine percent fertility
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily
Details on study schedule:
Each male mouse in the treated and control groups was caged with three females, which were allowed to stay with the male for 1 week. The female miewere necropsied 13 days following the mid-week of their caging and presumptive mating and the number of pregnant mice wasrecorded to determine percent fertility.
Doses / concentrations
Remarks:
Doses / Concentrations:0, 25 mg/kg/day,50 mg/kg/day,100 mg/kg/dayBasis:actual ingested
No. of animals per sex per dose:
Study on reproductive parameters of male mice-group 1, control (tap water)-5 male micegroup 2, Ginkgo biloba-25 mg/kg/day-5 male micegroup 3, Ginkgo biloba-50 mg/kg/day-5 male micegroup 4,Ginkgo biloba-100 mg/kg/day-5 male miceStudy rate of pregnancy and mean implants per female-group 1, control (tap water)-5 male micegroup 2, Ginkgo biloba-25 mg/kg/day-10 male mice and 30 female mice matedgroup 3, Ginkgo biloba-50 mg/kg/day-10 male mice and 30 female mice matedgroup 4,Ginkgo biloba-100 mg/kg/day-10 male mice and 30 female mice mated
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale:The dose of Ginkgo biloba was determined by (i) maximum tolerated dose (MTD) and (ii) human therapeutic dose with reference to the surface area rule. On basis of evaluated MTD (1.6 gm/kg), the doses of Ginkgo biloba selected were 25, 50 and 100 mg/kg/day corresponding to 1/64, 1/32 and 1/16, respectively.

Examinations

Parental animals: Observations and examinations:
REPRODUCTIVE ORGAN WEIGHT: Yes- Time schedule for examinations:last day of sub-chronic treatment-Organ weight-testes, caudae epididymis, seminal vesicles and prostate gland
Oestrous cyclicity (parental animals):
Not examined
Sperm parameters (parental animals):
Parameters examined in P male parental generations:spermatozoa motility, count and abnormalities
Litter observations:
Not applicable
Postmortem examinations (parental animals):
REPRODUCTIVE ORGAN WEIGHT: Yes
Postmortem examinations (offspring):
Not applicable

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
not specified

Reproductive function / performance (P0)

Reproductive function: sperm measures:
effects observed, treatment-related
Reproductive performance:
effects observed, treatment-related

Details on results (P0)

Effect on reproductive organ weight, sperm motility and count-significant increase in the mean weight of caudae epididymis at 50 and 100 mg/kg/day and prostate at 100 mg/kg/day of Ginkgo biloba. There was no significant effect of the treatment on either the sperm motility or the count.Effect on spermatozoa morphology-No significant effects observed.Effect on the rate of pregnancy and mean implants per female-decrease the rate of pregnancy and cause embryonic losses implantation.These changes were statistically significant at the higher dose (100 mg/kg/day).

Effect levels (P0)

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Dose descriptor:
NOAEL
Effect level:
25 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No effects reproductive organ weight, sperm motility and count,spermatozoa morphology.
Remarks on result:
other: no other details available
Dose descriptor:
LOAEL
Effect level:
50 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: significant increase in the mean weight of caudae epididymis and prostate.
Remarks on result:
other: no other details available
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: no change in the dead implants per pregnant female mice.
Dose descriptor:
LOAEL
Effect level:
100 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: decrease the rate of pregnancy and cause embryonic losses implantation.

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not specified

Effect levels (P1)

Dose descriptor:
other: not specified
Based on:
not specified
Sex:
not specified
Remarks on result:
other: not specified

Target system / organ toxicity (P1)

Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

Effect levels (F1)

Dose descriptor:
other: not specified
Based on:
not specified
Sex:
not specified
Remarks on result:
other: not specified

Target system / organ toxicity (F1)

Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F2 generation

Effect levels (F2)

Dose descriptor:
other: not specified
Based on:
not specified
Sex:
not specified
Remarks on result:
other: not specified

Target system / organ toxicity (F2)

Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
Based on the subchronic study in mice the following is assessed-NOAEL-P Male-25 mg/kg bw/day.LOAEL-P-Male-50 mg/kg bw/day.NOAEL-P-Female-50 mg/kg bw/day.LOAEL-P-Female-100 mg/kg bw/day.
Executive summary:

In 90 days subchronic study effect of Ginkgo Biloba was studied on reproductive parameters- spermatozoa motility, count and abnormalities and on rate of pregnancy and mean implants per female.Based on effecs observed the following NOAEL and LOAEL values were assessed-

NOAEL-P Male-25 mg/kg bw/day.

LOAEL-P-Male-50 mg/kg bw/day.

NOAEL-P-Female-50 mg/kg bw/day.

LOAEL-P-Female-100 mg/kg bw/day.