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Administrative data

Description of key information

ORAL

LD50 > 2 000 mg/kg, mouse (male/female), OECD 401, Ishida (1997)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
13 October 1997 to 15 December 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
mouse
Strain:
ICR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Crj:CD-1 (ICR)
- Age at study initiation: 6 weeks
- Weight at study initiation: 25.2 to 27.7 g (male) and 20.3 to 23.4 g (female)
- Fasting period before study: Mice were fasted a night before administration, approximately for 16 hours
- Housing: Animals were housed in floored plastic cages (W340xD400xH185mm)
- Diet: Ad libitum; free access to solid food
- Water: Ad libitum; free access to water (mains water)
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature: 23±3 °C
- Humidity: 50±20 % (relative)
- Air changes: 10 to 15 times per hour
- Photoperiod: 12 hours lighting a day (07:00 to 19:00)

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.5 w/v % concentration
- Amount of vehicle: 2000 mg/kg
- Justification for choice of vehicle: Oral route was selected as the administration route because it is widely used as general exposure.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A dose level of 2000mg/kg was selected in order to evaluate the basic toxicity of the test substance.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:

1) Observation of clinical signs
Clinical signs such as external appearance, nutritional status and behavior etc. were observed frequently until 6 hours after administration, and then once a day afterwards for 14 days.

2) Body weight measurement
The body weight was measured on the day of administration (immediately before administration) to determine the value as the basis of calculating dose volume. The body weight was also measured at a certain time (between 08:00~12:30) of day 1, 2, 3, 7, 10 and 14 after administration.

3) Pathological examination
After completion of the observation period of 14 days, animals were killed by exsanguination under ether anesthesia. External appearance and all organs and tissues including the head, the chest and the abdominal parts were observed and recorded.

- Necropsy of survivors performed: yes
Statistics:
Regarding the body weight, the mean body weight and the standard deviation were calculated for each group and the homogeneity of variance in each group was evaluated using F-test. The results were evaluated using Student t-test for the homogeneous variance, Aspin-Welch t-test was used for the non-homogeneous variance. The test was performed at the both end, 5 and 1 % was set as significant standard.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured at dose level of 2000 mg/kg.
Clinical signs:
No abnormality was observed in any animals in the observations of external appearance, nutritional status and behaviour.
Body weight:
The body weight development was almost the same between 2000mg/kg administered group and control group in both male and female.
Gross pathology:
There was no abnormality in any animals in the macroscopical observation of external appearance, organ and tissue of head, chest and abdominal parts.

TABLE 1: BODY WEIGHT (Male)

 

                                   Day after administration                                             GAIN

Dose

mg/kg

 

0

1

2

3

7

10

14

0-14

0

No.

Mean

S.D.

5

26.6

0.9

5

30.1

1.3

5

30.5

1.2

5

31.0

1.1

5

32.6

1.8

5

32.6

2.0

5

34.4

1.8

5

7.8

1.4

2000

No.

Mean

S.D

5

26.5

0.7

5

30.3

1.0

5

30.8

1.0

5

31.0

1.0

5

32.8

0.7

5

32.8

0.7

5

35.0

0.7

5

8.4

0.3

TABLE 2: BODY WEIGHT (Female)

 

                                                         Day after administration                                         GAIN

Dose

mg/kg

 

0

1

2

3

7

10

14

0-14

0

No.

Mean

S.D.

5

21.2

0.7

5

24.6

0.9

5

24.8

0.5

5

24.1

0.9

5

26.0

0.9

5

26.8

1.4

5

27.4

1.4

5

6.2

0.9

2000

No.

Mean

S.D

5

21.3

1.2

5

23.7

1.5

5

24.5

1.2

5

24.6

1.2

5

25.2

1.1

5

25.5

1.5

5

26.5

1.9

5

5.2

0.9

unit: g

No significant difference between treated group and control.

Interpretation of results:
not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, no change was observed by the single oral administration of 2000 mg/kg; therefore, the LD50 is above 2000 mg/kg.
Executive summary:

The acute oral toxicity of the test material was investigated in a study which was performed following similar or equivalent methodology to the standardised guideline OECD 401.

During the study, 5 male and 5 female (ICR) mice received a test material dose of 2000 mg/kg administered in a 0.5 w/v % carboxymethylcellulose sodium solution via gavage. 

The observation period was 14 days in which external appearance, nutritional value and behaviour were examined.

After completion of the observation period of 14 days, animals were killed by exsanguination under ether anaesthesia. External appearance and all organs and tissues including the head, the chest and the abdominal parts were observed and recorded.

No deaths were observed in animals administered 2000 mg/kg and the lethal dose level was estimated to exceed 2000 mg/kg in both male and female.

No effect related to the test material administration was observed in clinical signs, body weight and gross pathology.

Under the conditions of this study, the acute oral LD50 of the test material in male and female (ICR) mice was greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Study conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

One study on the test material is available (Ishida, 1997) and there are two more studies available as read-across (Ichimura & Kirimura, 1969 and Kiss, 2012a, respectively). The studies collectively have a weight of evidence approach.

 

Ishida, 1997 awarded a reliability score of 2, in accordance with the criteria set out in Klimisch 1997; the study was conducted to GLP in accordance and was performed following similar or equivalent methodology to the standardised guideline OECD 401with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results. During the study, 5 male and 5 female (ICR) mice received a test material dose of 2 000 mg/kg administered in a 0.5 w/v % carboxymethylcellulose sodium solution via gavage. 

The observation period was 14 days in which external appearance, nutritional value and behaviour were examined. After completion of the observation period of 14 days, animals were killed by exsanguination under ether anaesthesia. External appearance and all organs and tissues including the head, the chest and the abdominal parts were observed and recorded.

No deaths were observed in animals administered 2 000 mg/kg and the lethal dose level was estimated to exceed 2 000 mg/kg in both male and female. No effect related to the test material administration was observed in clinical signs, body weight and gross pathology. Under the conditions of this study, the acute oral LD50 of the test material in male and female (ICR) mice was greater than 2000 mg/kg.

 

Kiss, 2012a is the second study in this weight of evidence approach. The study was performed using read across substance, sodium 5-oxo-L-prolinate. The study was conducted under GLP conditions and in line with OECD 423 and EU Method B. 1 tris, according to the acute toxic class method. The study was assigned a reliability score of 2 in line with the principles for assessing data quality as defined by Klimisch (1997). Two groups of three females were dosed with the test material, formulated in distilled water, at 2000 mg/kg bw via oral gavage. Animals were observed for 14 days post treatment for mortality, clinical signs of toxicity, changes in body weight and macroscopic changes at necropsy.

Under the conditions of the study, no mortalities or signs of toxicity were observed in treated animals. The LD50 was therefore considered to be greater than 2000 mg/kg bw. As this study has been used for read across, and performed to standardised guidelines and under GLP conditions, it was awarded a reliability score of 2 in accordance with the criteria for assessing data quality as set forth by Klimisch et al. (1997).

 

Ichimura & Kirimura, 1969 is the third study in this weight of evidence approach, and was performed using read across substance, sodium 5-oxo-DL-prolinate. Read across is considered to be suitable based on structural similarities between the two substances. The study was performed following similar or equivalent methodology to the standardised guideline OECD 401. Acute oral toxicity of the material was assessed using optional test groups of dd-line mice, which consisted of 10 mice in each group. In the case of the control group, solvent alone was administered in accordance with the case of the test groups. The dose levels administered are as follows: 7.02, 8.19, 9.36, 10.8, 12.3 and 14.0 g/kg. These concentrations were administered to each mouse in a constant volume per 10 g of mouse body weight by a stomach tube. The animals were under observation for 7 days and any mortality was recorded.

Under the conditions of the study, the LD50 was found to be 10.4 g/kg (95 % confidence limit between 9.08 and 11.8 g/kg). The study has been translated into English, however the full the study report is not available; therefore there is insufficient information to how the study was performed, hence this study has been designated a reliability score of 4, in accordance with the criteria for assessing data quality as set forth by Klimisch et al. (1997).

Justification for selection of acute toxicity – oral endpoint

Only one study available on this substance.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to acute toxicity.