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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

Constituent 1
Chemical structure
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.