Registration Dossier

Administrative data

Description of key information

ORAL

Key study (Read-across from structurally similar substance): LD50 > 2000 mg/kg bw, rat (female), OECD 423, Kiss (2012a)

Supporting studies:

- Registered substance: LD50 > 2000 mg/kg bw, mouse (male/female), equivalent to OECD 401, Ishida (1997)

- Read-across from structurally similar substance: LD50 10400 mg/kg bw, mouse (male), equivalent to OECD 401, Ichimura & Kirimura (1969)

INHALATION

In accordance with point 8.5.2, Column 2 (Specific rules for adaptation from Column 1), Annex VIII of Regulation (EC) No. 1907/2006, an acute inhalation study does not need to be performed as use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. The acute toxicity endpoint has been addressed by assessing the toxicity via the oral and dermal routes, which are more appropriate when considering the use pattern of this substance.

DERMAL (Read-across from structurally similar substance)

Under the conditions of the study on the read-across substance, no mortalities, systemic or local signs of toxicity were observed in animals treated at 2 000 mg/kg bw. The LD50 was therefore considered to be greater than 2 000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07 March 2012 to 22 March 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Reason / purpose:
other: read-across target
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: CRL: (WI)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10 to 11 weeks old.
- Weight at study initiation: 220 to 235 g
- Fasting period before study: Animals were fasted the night before treatment, and then returned three hours after treatment.
- Housing: In groups of three, in polypropylene/polycarbonate cages.
- Diet: Complete diet for rats and mice, ad libitum.
- Water: tap water from the municipal supply ad libitum.
- Acclimation period: At least 20 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15 - 20 per hour.
- Photoperiod (hrs dark / hrs light): 12 hours per day, between 06:00 and 18:00 hours.

IN-LIFE DATES: From: 07 March 2012 To: 21/22 March 2012
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Distilled
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test amterial was freshly formulated at a concentration of 200 mg/mL in the vehicle, on the day of administration. The formulation container was stirred continuously up to finishing the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: The initial dose level was selected by the study director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

DOSING
- Method: A group of three females were tested at the dose level initially, based on the findings a second group was dosed to confirm the results.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Three females per group.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
> Weighing: Body weights were recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
> Clinical: Observations were recorded at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: Yes, and macroscopic examination was performed on all animals. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities were observed in either group dosed at 2000 mg/kg bw.
Clinical signs:
No treatment related observations were made during the 14 day observation period.
Body weight:
Body weight gains of treated animals were within the expected range, and showed no indication of treatment related effects. The mean bodyweight gain for animls from groups 1 and 2 was 20.7 ± 8.0 g.
Gross pathology:
No treatment related effects were observed.
Interpretation of results:
other: Not classified according to EU criteria.
Conclusions:
Under the conditions of the study, no mortalities or signs of toxicity were observed in animals treated at 2000 mg/kg bw. The LD50 was therefore considered to be greater than 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test material was determined in a study conducted under GLP conditions and in line with OECD 423 and EU Method B. 1 tris, according to the acute toxic class method. 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.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read-across material
Justification for type of information:
Read-across from a structurally similar substance. Please refer to the RAAF report (section 13) for further information/ justification.
Reason / purpose:
read-across source
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
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.
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
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:
other: Not classified according to EU criteria
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:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
12 March 1969
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study has been awarded a reliability score of 4, in accordance with the criteria set out in Klimisch, 1997. The study report has been translated into English; however, the full translation of the study report is not available. Therefore there is simply not enough information regarding how the study was performed to be able to give the study a higher reliability score.
Reason / purpose:
other: read-across target
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Remarks:
- the translation does not appear to be the full study report. Therefore it is not clear whether certain parameters were not examined or not included in the translated report.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
other: dd-line
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 13.5 to 16.4 g
- Fasting period before study: 13 to 15 hours



Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.5 w/v % concentration sodium carboxymethyl cellulose

MAXIMUM DOSE VOLUME APPLIED: 14.0 g/kg

DOSAGE PREPARATION (if unusual):
Among the samples, those soluble in water were dissolved in ion-exchanged water or in distilled water to the concentrations required and those not sufficiently soluble in water were ground in an agate mortar previously and then suspended in an 0.5 % aqueous solution of sodium carboxymethyl cellulose to the concentrations required and they they were orally administered in accordance with the case of the test groups.


Doses:
7.02, 8.19, 9.36, 10.8, 12.3 and 14.0 g/kg
No. of animals per sex per dose:
10 males/group (Total 70 animals)
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Observations were made at 0 hour, 6-7 hours then every 24 hours there after.
Statistics:
Litchfield-Wilcoxon method was used for calculation of the LD50 value.
Sex:
male
Dose descriptor:
LD50
Effect level:
10 400 mg/kg bw
Based on:
test mat.
95% CL:
>= 9 080 - <= 11 800
Mortality:
No mortalities were observed in the control group or those dosed at the lowest dose of 7.02 g/kg. At the dose levels of 8.19, 9.36, 10.8, 12.3 and 14.0 g/kg there were 2, 3, 6, 7 and 9 mortalities recorded, respectively.

Table 1: Relation between the amount of DL-PCA-Na administered and the mortality of mouse

Administration Amount

(g/kg)

Elapsed time after administration and

number of surviving animals

At 168 hours after administration

0

6-7

24

48

72

96

120

144

168

Number of dead animals

Mortality

(%)

0

10

10

10

10

10

10

10

10

10

0

0

7.02

10

10

10

10

10

10

10

10

10

0

0

8.19

10

10

10

9

8

8

8

8

8

2

20

9.36

10

9

9

9

9

9

9

8

7

3

30

10.8

10

9

4

4

4

4

4

4

4

6

60

12.3

10

9

3

3

3

3

3

3

3

7

70

14.0

10

4

1

1

1

1

1

1

1

9

90

From the above results, the LD50 and the 95 confidence limit of DL-PCA-Na were determined as follows:

LD50: 10.4 g/kg (95 % confidence limit between 9.08 and 11.8 g/kg).

Interpretation of results:
other: Not classified according to EU criteria.
Conclusions:
Under the conditions of the study, the LD50 was 10.4 g/kg (95 % confidence limit between 9.08 and 11.8 g/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.

The acute oral toxicity of the test 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.

No mortalities were observed in the control group or those dosed at the lowest dose of 7.02 g/kg.

At the dose levels of 8.19, 9.36, 10.8, 12.3 and 14.0 g/kg there were 2, 3, 6, 7 and 9 mortalities recorded, respectively.

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).

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read-across material
Justification for type of information:
Read-across from a structurally similar substance. Please refer to the RAAF report (section 13) for further information/ justification.
Reason / purpose:
read-across source
Sex:
male
Dose descriptor:
LD50
Effect level:
10 400 mg/kg bw
Based on:
test mat.
95% CL:
>= 9 080 - <= 11 800
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
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

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 April 2012 to 18 April 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Reason / purpose:
other: Read-across target
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CRL: (WI)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young rats
- Weight at study initiation: 214 - 266g
- Housing: Individually in polypropylene/polycarbonate cages.
- Diet: Complete diet for rats and mice, ad libitum.
- Water: Municipal tap water, ad libitum.
- Acclimation period: 6 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15 - 20 per hour.
- Photoperiod (hrs dark / hrs light): 12 hours from 06:00 to 18:00 hours daily.

IN-LIFE DATES: From: 04 April 2012 To: 18 April 2012.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: On the back of each animal.
- % coverage: Approximately 10 % of the whole body surface area.
- Type of wrap if used: The test material was placed onto a gauze pad. The gauze pad was fixed with a hypoallergenic plaster and the entire trunk of the animal was then wrapped with semi occlusive plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With body temperature water.
- Time after start of exposure: 24 hours.

TEST MATERIAL
Sufficient water to damp the material was used to ensure good contact with the skin.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> Clinical: Observations were performed on the day of treatment at 1 and 5 hours after application of the test material and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
> Bodyweight: Recorded on Day 0 (before exposure) and on Days 7 and 14.
- Necropsy of survivors performed: Yes, after examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities were observed in either males or females dosed at 2000 mg/kg bw.
Clinical signs:
No treatment related systemic or local signs of toxicity observed during the 14 day observation period.
Body weight:
Body weight gains of treated animals were within the expected range, and showed no indication of treatment related effects. The mean bodyweight gain for males was 106.6 ± 21.0 g and 26.4 ± 7.7 g for females.
Gross pathology:
No treatment related effects were observed. Bilateral uterine dilatation with clear fluid seen in 2/5 females was regarded as common background.
Interpretation of results:
other: Not classified according to EU criteria
Conclusions:
Under the conditions of the study, no mortalities, systemic or local signs of toxicity were observed in animals treated at 2000 mg/kg bw. The LD50 was therefore considered to be greater than 2000 mg/kg bw.
Executive summary:

The acute dermal toxicity of the test material was determined in a study conducted under GLP conditions and in line with OECD 402, EU Method B. 3 and EPA OPPTS 870.1200, according to the standard acute method. Five male and five female rats were exposed to the test material in a limit test at 2000 mg/kg bw for 24 hours under an occlusive dressing.

Under the conditions of the study, no mortalities or treatment related systemic or local signs of toxicity were observed in animals treated at 2000 mg/kg bw. The LD50 was therefore considered to be greater than 2000 mg/kg bw.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read-across material.
Justification for type of information:
Read-across from a structurally similar substance. Please refer to the RAAF report (section 13) for further information/ justification.
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

ORAL

Key study (Read-across from structurally similar substance), Kiss (2012a)

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 1 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.

Supporting studies:

- Ishida (1997)

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 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.

- Ichimura & Kirimura (1969) (Read-across from structurally similar substance)

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).

INHALATION

In accordance with point 8.5.2, Column 2 (Specific rules for adaptation from Column 1), Annex VIII of Regulation (EC) No. 1907/2006, an acute inhalation study does not need to be performed as use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. The acute toxicity endpoint has been addressed by assessing the toxicity via the oral and dermal routes, which are more appropriate when considering the use pattern of this substance.

DERMAL (Read-across from structurally similar substance)

The acute dermal toxicity of the test material was determined in a study conducted under GLP conditions and in line with OECD 402, EU Method B. 3 and EPA OPPTS 870.1200, according to the standard acute method. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Five male and five female rats were exposed to the test material in a limit test at 2000 mg/kg bw for 24 hours under an occlusive dressing.

Under the conditions of the study, no mortalities or treatment related systemic or local signs of toxicity were observed in animals treated at 2000 mg/kg bw. The LD50 was therefore considered to be greater than 2000 mg/kg bw.

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.