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Description of key information

- In a study according to OECD guideline 423, GLP, Reliability 2, the LD50 of the source substance Sophorolipid C18 unsatd. acid in the female Sprague-Dawley CD strain was estimated as being greater than 6645 mg/kg bw (equivalent to 2000 mg active ingredient/kg bw). This LD50 refers to the acid form of the target UVCB substance.

- In the publication by Ikeda et al. (1986), the LD50 of Sophorolipid C16-18 unsatd. lactone was determined in 10 fasted male mice per dose group and calculated to be 12500 mg/kg based on test material. This LD50 refers to the lactone form of the target UVCB substance.

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:
weight of evidence
Study period:
no information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
7 days observation
GLP compliance:
no
Test type:
standard acute method
Species:
mouse
Strain:
ICR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Shizuoka Prefecture Agricultural Cooperative Association for Laboratory Animals
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 25-29 g
- Fasting period before study: yes, 16-18 hours before the administration
- Housing: polycarbonate cages with wood chip floor covering and 5 animals per cage
- Diet: solid feed (CE-2, CLEA Japan, Inc.) ad libitum
- Water: tap water ad libitum
- Acclimation period: not reported
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2 °C
- Humidity (%): 55 ± 10 %,
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): not reported
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 37.5 w/v suspension
- Amount of vehicle (if gavage): not specified
Doses:
7230, 8680, 10420, 12500 and 15000 mg/kg bw
No. of animals per sex per dose:
10 males per dose level
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: yes
Statistics:
LD50 value was calculated with the Litchfield and Wilcoxon method using the mortality rate.
Preliminary study:
not applicable
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 12 500 mg/kg bw
Based on:
test mat.
95% CL:
>= 11 060 - <= 14 130
Mortality:
At the highest dose level of 15000 mg/kg bw, all 10 animals died in between 1 day after administration.
At the dose level of 12500 mg/kg bw, 5 animals died in between 1 day after administration.
At the dose level of 10420 mg/kg bw, 1 animal died in between 1 day after administration.
No other deaths were reported in the 7-day observation period.

Clinical signs:
reduced locomotion, sedation, hyperventilation, weakness of the extremities, loose stool, diarrhoea, piloerection
Body weight:
not reported
Gross pathology:
Individuals which had died showed hyperemia or mild bleeding from the pyloric region of the stomach to the small intestine. No specific abnormalities could be found in the surviving individuals.

Table 1: Deaths of mice and LD50 after oral installation of the test item.

 

Number of dead animals during observation period (day)

 

Dose level [mg/kg bw]

0-1

2-4

5-7

Lethality [%]

LD50 and 95 % CL [mg/kg bw]

7230

0

0

0

0

12500

(11060 – 14130)

8680

0

0

0

0

10420

1

0

0

10

12500

5

0

0

50

15000

10

0

0

100

 

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test item in male mice was determined to be 12500 mg/kg bw.
Executive summary:

The publication by Ikeda et al. (1986) reports the determination of the LD50 value of Sophorolipid in its lactone form. The study has not been conducted according to an OECD guideline, but generally meets the principle for determination of acute oral toxicity and has been described in sufficient detail. The study is therefore considered as acceptable for classification purposes.

In this study, 10 fasted male mice per dose group were administered the test item p.o. via gavage. The dose groups were 7230, 8680, 10420, 12500 and 15000 mg/kg bw. The animals were observed for 7 days. Necropsy was conducted after death or in all surviving animals after the observation period. Clinical signs were reduced locomotion, sedation, hyperventilation, weakness of the extremities, loose stool, diarrhoea and piloerection.

The LD50 of Sophorolipid, lactone form, was calculated to be 12500 mg/kg based on test material. However, the percentage of active ingredient in the test item is not reported. The test item is described as a semi-solid colloid which may indicate rather high content of active ingredient. Taking into account that the Sophorolipid raw material after filtration and decanting is a solution consisting of approximately 50-60 % Sophorolipids mainly in the lactone form, the LD50 would here still be in a range that does not need classification.

 

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties, based on the following underlying similar generic structure and similar metabolism pathways. There are only differences in the ratio of the different structures (differentiation between acid and lactone form). For details, please refer to the justification for read-across.
Reason / purpose:
read-across source
Test type:
standard acute method
Species:
mouse
Strain:
ICR
Sex:
male
Route of administration:
oral: gavage
Vehicle:
water
Doses:
7230, 8680, 10420, 12500 and 15000 mg/kg bw
No. of animals per sex per dose:
10 males per dose level
Control animals:
no
Statistics:
LD50 value was calculated with the Litchfield and Wilcoxon method using the mortality rate.
Preliminary study:
not applicable
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 12 500 mg/kg bw
Based on:
test mat.
95% CL:
>= 11 060 - <= 14 130
Mortality:
At the highest dose level of 15000 mg/kg bw, all 10 animals died in between 1 day after administration.
At the dose level of 12500 mg/kg bw, 5 animals died in between 1 day after administration.
At the dose level of 10420 mg/kg bw, 1 animal died in between 1 day after administration.
No other deaths were reported in the 7-day observation period.

Clinical signs:
reduced locomotion, sedation, hyperventilation, weakness of the extremities, loose stool, diarrhoea, piloerection
Body weight:
not reported
Gross pathology:
Individuals which had died showed hyperemia or mild bleeding from the pyloric region of the stomach to the small intestine. No specific abnormalities could be found in the surviving individuals.

Table 1: Deaths of mice and LD50 after oral installation of the test item.

 

Number of dead animals during observation period (day)

 

Dose level [mg/kg bw]

0-1

2-4

5-7

Lethality [%]

LD50 and 95 % CL [mg/kg bw]

7230

0

0

0

0

12500

(11060 – 14130)

8680

0

0

0

0

10420

1

0

0

10

12500

5

0

0

50

15000

10

0

0

100

 

Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of the test item in male mice was determined to be 12500 mg/kg bw.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2004-11-23 to 2004-11-25
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 216-243 g
- Fasting period before study: overnight
- Housing: polypropylene cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): 30-70 %
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continous light, twelve hours continous dark
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 6645 mg/kg bw (equvalent to 2000 mg active ingredient/kg bw)

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using all available information on the toxicity of the test material
Doses:
6645 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: 1/2, 1, 2, 4 hours after dosing and subsequently once daily for 14 days; weighing: at days 0, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
act. ingr.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 6 645 mg/kg bw
Based on:
test mat.
Mortality:
no mortalty observed
Clinical signs:
no abnormal signs
Body weight:
All animals showed expected gains in body weight over the study period
Gross pathology:
No abnormalities were noted.

Individual body weights and weekly body weight changes

Dose level (mg/kg bw)

Animal number and sex

Body weight (g) at day

Body weight gain during week

0

7

14

1

2

6645*

2-0 Female

241

276

290

35

14

2-1 Female

243

265

288

22

23

2-2 Female

216

235

257

19

16

3-0 Female

240

270

288

30

18

3-1 Female

237

264

274

27

10

3-2 Female

244

270

275

26

5

*: = equivalent to 2000 mg active ingredient/kg bw

Interpretation of results:
GHS criteria not met
Conclusions:
No mortality, signs of systemic toxicity or abnormalities at necropsy were observed. All animals showed expected gains in body weight over the study period.
Executive summary:

The acute oral toxicity of the substance to rats was investigated in a study according to OECD Guideline 423 (Acute oral toxicity - acute toxic class method; adopted 17 December 2001). A group of three fasted females was treated with the test material at a dose level of 6645 mg/kg bw (eqivalent to 2000 mg active ingredient/kg bw). This was followed b a further group of threee fasted females at the same dose level.

The test material was administered undiluted. Clinical signs and body weight development were monitored during the study. All animals were subjected to necropsy. No mortality, signs of systemic toxicity or abnormalities at necropsy were observed. All animals showed expected gains in body weight over the study period.

It can be concluded that the acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain was estimated as being greater than 6645 mg/kg bw (equivalent to 2000 mg active ingredient/kg bw).

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The toxicological profile for systemic endpoints is expected to be similar for target substance Sophorolipids: fermentation products of glucose and fatty acids, C18-unsatd., esters with glycerol with yeast Candida Bombicola, partially hydrolysed when compared to the source substance Sophorolipid, SLH solution. Read-across is expected to be reliable including the data on acute oral toxicity, sensitization and gene toxicity in vitro.
For further information, please see the justification for read-across in chapter 13.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
6645 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
act. ingr.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 6 645 mg/kg bw
Based on:
test mat.
Mortality:
no mortalty observed
Clinical signs:
no abnormal signs
Body weight:
All animals showed expected gains in body weight over the study period
Gross pathology:
No abnormalities were noted.

Individual body weights and weekly body weight changes

Dose level (mg/kg bw)

Animal number and sex

Body weight (g) at day

Body weight gain during week

0

7

14

1

2

6645*

2-0 Female

241

276

290

35

14

2-1 Female

243

265

288

22

23

2-2 Female

216

235

257

19

16

3-0 Female

240

270

288

30

18

3-1 Female

237

264

274

27

10

3-2 Female

244

270

275

26

5

*: = equivalent to 2000 mg active ingredient/kg bw

Interpretation of results:
GHS criteria not met
Conclusions:
No mortality, signs of systemic toxicity or abnormalities at necropsy were observed. All animals showed expected gains in body weight over the study period. It can be concluded that the acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain was estimated as being greater than 6645 mg/kg bw (equivalent to 2000 mg active ingredient/kg bw).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Acute oral toxicity values are derived from a read-across approach based on a scientific publication and a well-documented guideline study. Thus, the database is regarded to be of high quality.

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

In a read-across approach, the acute oral LD50 was determined from a guideline study and a scientific publication.

The toxicological profile for systemic endpoints is expected to be similar for target substance Sophorolipids: fermentation products of glucose and fatty acids,  C18-unsatd., esters with glycerol with yeast Candida Bombicola, partially hydrolysed when compared to the source substances. Read-across is expected to be reliable including the data on acute oral toxicity, sensitization and gene toxicity in vitro.

a. OECD guideline 423 study:

The acute oral toxicity of the substance to rats was investigated in a study according to OECD Guideline 423 (Acute oral toxicity - acute toxic class method; adopted 17 December 2001). A group of three fasted females was treated with the test material at a dose level of 6645 mg/kg bw (eqivalent to 2000 mg active ingredient/kg bw). This was followed b a further group of threee fasted females at the same dose level.

The test material was administered undiluted. Clinical signs and body weight development were monitored during the study. All animals were subjected to necropsy. No mortality, signs of systemic toxicity or abnormalities at necropsy were observed. All animals showed expected gains in body weight over the study period.

It can be concluded that the acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain was estimated as being greater than 6645 mg/kg bw (equivalent to 2000 mg active ingredient/kg bw).

b. scientific publication by Ikeda et al. (1986):

The publication by Ikeda et al. (1986) reports the determination of the LD50 value of Sophorolipid in its lactone form. The study has not been conducted according to an OECD guideline, but generally meets the accepted scientific principle for determination of acute oral toxicity and has been described in sufficient detail. The study is therefore considered as acceptable for classification purposes.

In this study, 10 fasted male mice per dose group were administered the test item p.o. via gavage. The dose groups were 7230, 8680, 10420, 12500 and 15000 mg/kg bw. The animals were observed for 7 days. Necropsy was conducted after death or in all surviving animals after the observation period. Clinical signs were reduced locomotion, sedation, hyperventilation, weakness of the extremities, loose stool, diarrhoea and piloerection.

The LD50 of Sophorolipid, lactone form, was calculated to be 12500 mg/kg based on test material. However, the percentage of active ingredient in the test item is not reported. The test item is described as a semi-solid colloid which may indicate rather high content of active ingredient. Taking into account that the Sophorolipid raw material after filtration and decanting is a solution consisting of approximately 50-60 % Sophorolipids mainly in the lactone form, the LD50 would here still be in a range that does not need classification.

Overall, in this read-across approach, the LD50 of the test item was determined to be > 2000 mg/kg bw based on active ingredient.

There are no studies available on acute toxicity via dermal or inhalation route.

 

Justification for classification or non-classification

The acute oral toxicity of the test item is > 2000 mg/kg bw based on active ingredient and therefore, GHS criteria for acute oral toxicity are not met.