Genipin

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Part of pre-clinical research for the medical use of genipin

Justification for type of information:

Acute oral toxicity study on rats performed as part of pre-clinical research on metabolic processes.
Peer-reviewed published research
In view of the observed mortality, the study can be used to support classification.
No further animal testing can be justified to support acute oral toxicity

Data source

Reference

Reference Type:

publication

Title:

Metabolism and pharmacokinetics of genipin and geniposide in rats

Author:

Hou et al

Year:

2008

Bibliographic source:

Food Chem Toxicol. 2008;46:2764–2769

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Principles of method if other than guideline:

Two dose levels administered orally to 9 rats
The purpose of the study was to look for excretion of metabolites, but in view of mortality being observed, the study provides details to allow classification

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Genipin

EC Number:

636-196-5

Cas Number:

6902-77-8

Molecular formula:

C11H14O5

IUPAC Name:

Genipin

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Technical grade obtained from Challenae Bioproducts Co. Ltd

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Administered after 12 hours fasting

Doses:

100 and 200 mg/kg single dose

No. of animals per sex per dose:

9

Control animals:

no

Details on study design:

Testing was to look for metabolic activity of genipin and the crude plant extracts
Blood samples were taken frequently over the period from 5 minutes and up to 7 days dosing, with analysis performed by HLPC to detect the parent compound and probable metabolites.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

approximate LD50

Remarks:

Resulted in death of 7 out of 9 animals

Effect level:

200 mg/kg bw

Based on:

test mat.

Mortality:

7 out of 9 males at 200 mg/kg
No mortality at 100 mg/kg

Clinical signs:

other:

Other findings:

Blood samples taken at time points after administration showed that the sulphate form of genipin emerged rapidly in plasma, whereas the parent form of genipin was not detected. This was a clear indication that rapid and extensive sulphation had occurred during the first pass through intestine and liver

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Although a precise LD50 was not determined, it is noted that this would be between 100 and 200 mg/kg and allowing classification

Conclusions:

A precise discriminating dose or precise LD50 was not possible to determine based on these results.
However, based on the absence of mortality at 100 mg/kg and mortality of > 70% at 200 mg/kg, an LD can be assumed to be in the range leading to Acute Tox 3 for classification purposes.