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Administrative data

Description of key information

L-Cystine was found to be practically non-toxic after oral and dermal application.

Key value for chemical safety assessment

Acute toxicity: via oral route

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Reference
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
Qualifier:
equivalent or similar to
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
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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
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
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:
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.
Body weight:
Although suppression of weight increase was found 1 to 2 days after administration in both males and females, a progressive increase in body
weight was subsequently exhibited.
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
25 000 mg/kg bw

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study performed under GLP conditions
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
dressing: gauze and non-irritating tape
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 male and 5 female
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality
Clinical signs:
No signs of toxicity. Scratches were observed in one male animal.
These signs of irritation were not reversible within the observation period (14 days).
Body weight:
Very slight weight loss in one female animal during the first week but weight gain during the second week.
Gross pathology:
No special findings
Other findings:
None
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the condition of the present study, single dermal application of the test item L-Cystine to rats at a dose of 2000 mg/kg body weight was
associated with neither mortality nor signs of toxicity but slight signs of irritation.
Executive summary:

The dermal LD50 was determined to be > 2000 mg L-Cystine / kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

L-Cystine was tested in an acute oral toxicity study in Wistar rats (10/sex/dose). The administratinon dose was 10000 mg/kg and 25000 mg/kg of bw, administered via a feeding tube. One female specimen died in the cystine 25000 mg/kg group. No change in the animals' symptoms were found during the seven days following administration; no particular findings were observed in the autopsies.

The LD50 value was at least 25000 mg/kg.

Under the condition of a OECD 402 guideline study, single dermal application (24 h, semiocclusive) of the test item L-Cystine to rats (5 male and 5 female animals) at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity but slight signs of irritation (scratches were observed in one male animal). These signs of irritation were not reversible within the observation period (14 days).

The dermal LD50 was determined to be > 2000 mg L-Cystine / kg body weight.


Justification for selection of acute toxicity – oral endpoint
Comparable to guideline study with acceptable restrictions: article in Japanese, has been translated into English.

Justification for selection of acute toxicity – dermal endpoint
Guideline study according to OECD 402.

Justification for classification or non-classification

The oral LD50 in an acute rat study was found to be > 25000 mg/kg and results in non-classification for the endpoint.

The dermal LD50 in an scute rat study was found to be > 2000 mg/kg and results in non-classification for the endpoint.