Cystine

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:

other: Comparable to guideline study with acceptable restrictions: article in Japanese, has been translated into English

Data source

Reference

Reference Type:

publication

Title:

Acute toxicity test of Cystenosine and its constituent ingredients inosine and cystine in rats

Author:

Yoichiro Kawai, Masaharu Okai, Shuji Takeshita, Masafumi Tomita, Hidetoshi Nakagawa, Tokio Yoshinaka, Ichisuke Kawahara, Hiromasa Kawai

Year:

1978

Bibliographic source:

Oyo Yakuri Pharmacometrics 15(2), 199-221 (in japanese)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Principles of method if other than guideline:

Two dose groups were tested and the findings recorded.
The oral LD50 could not be detemined.

GLP compliance:

not specified

Test type:

other: two dose groups were tested

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cystine

EC Number:

200-296-3

EC Name:

Cystine

Cas Number:

56-89-3

Molecular formula:

C6H12N2O4S2

IUPAC Name:

cystine

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5 weeks
- Fasting period before study: 16h
- Housing: seperate cages
- Diet: CA-1 pellets
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 5% gum arabic aqueous solution

Details on oral exposure:

Cystine was suspended in 5% gum arabic aqueous solution, which weas adminstered at a dose of 5 mL/100g of bw. The administratinon dose was
10000 mg/kg or 25000 mg/kg of bw, which is the maximum allowable administration quantity, and the administration was given orally,
forcibly and using a feeding tube.

Doses:

5 mL/100g of bw
The administratino dose was 10000 mg/kg or 25000 mg/kg of bw.

No. of animals per sex per dose:

10/sex/group

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
- Other examinations performed: symptom and body weight changes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 25 000 mg/kg bw

Based on:

test mat.

Mortality:

After 48 h one rat died but the remaining rats returned to normal by 72 hours.

Clinical signs:

other: A decrease in spontaneous exercise was seen in two or three of the females 24 to 48 hours after administration, a drop in body temperature and dirtying around the lower abdomen were observed.

Gross pathology:

The results of the autopsy showed punctatebleeding on the stomach fundus and hematuria in the bladder, though there were no particular abnormal findings in the living specimens.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: Japan

Conclusions:

One female specimen died in the cystine 25000 mg/kg group.
The LD50 value was at least 25000 mg/kg.

Executive summary:

One female specimen died in the cystine 25000 mg/kg group.

The LD50 value was at least 25000 mg/kg.