(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-enecarboxylic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted under GLP conditions and in accord. with EEC directive 96/54, part 5.1 tris "acute toxicity-oral, acute toxic class method" and OECD guideline No. 423.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-enecarboxylic acid

EC Number:

205-334-2

EC Name:

(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-enecarboxylic acid

Cas Number:

138-59-0

Molecular formula:

C7H10O5

IUPAC Name:

(3R,4S,5R)-3,4,5-trihydroxycyclohex-1-enecarboxylic acid

Details on test material:

- Physical state : white powder
- Analytical purity : 98,9 %
- Test substance storage : in refrigerator in the dark
- Stability under storage conditions : stable

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals
- Source : Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation : approx. 9 weeks old
- Body weight variation : did not exceed +/- 20% of the sex mean
- Identification : Earmark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1 % aqueous carboxymethyl cellulose

Details on oral exposure:

Dose level (volume) : 2000 mg/kg (10ml/kg) body weight

Doses:

Single dosage, on day 1

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

The toxicity of the test substance was assessed by stepwise treatment of groups of 3 animals. The first group was treated at a dose level of 2000 mg/kg body weight. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were to be taken into account for determination of the time interval between the dose groups.

Obervations

- Mortality/viability : twice daily

- Body weight : days 1 (pre-administration), 8 and 15

- clinical signs : at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded;
Maximum grade 4 : grading slight (1) to very severe (4)
Maximum grade 3 : grading slight (1) to severe (3)
Maximum grade 1 : presence is scored (1).

- Necropsy : at the end of the observation period, all animals were sacrified by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured

Clinical signs:

other: Hunched posture and or piloerection were noted among the animals on days 1 and 2.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of shikimic acid in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off was considered to exceed 5000 mg/kg body weight.

Executive summary:

Assessment of acute oral toxicity with shikimic acid in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in OECD No 423 "Acute Oral Toxicity; Acute Toxic Class Method".

Shikimic acid was administrated by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Macroscopic examination was performed after terminal sacrifice (day 15).

No mortality occured.

Hunched posture and piloerection were noted among the animals on days 1 and 2.

The mean body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic post mortem examination on the animals.

The oral LD50 value of shikimic acid in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results and according to EC criteria for classification and labeling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), shikimic acid does not have to be classified and has no obligatory labeling requirement for oral toxicity.