Sucrose and glycerol, reaction products with C12-18, C18unsatd. fatty acids

Endpoint summary

Description of key information

The oral LD50 value for Sucroglyceride C12-18, C18unsatd. is > 2000 mg/kg bw . 
This oral LD50 value is supported by the LD50 values > 2000 mg/gkg bw obtained for three read-across substances Sucroglyceride C12,  Stearic acid, esters with methyl α-D-glucoside and Isostearic acid, esters with methyl α-D-glucoside.
The dermal LD50 value, determined for the read-across substance Isostearic acid, esters with methyl α-D-glucoside is > 2000 mg/kg bw.
The dermal LD50 value for Sucroglyceride C12-18, C18unsatd., derived from the read-across data, is also 2000 mg/kg bw. 
An LC50 for inhalation was not determined. 

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:

key study

Study period:

August 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: m: 182 - 201g; f: 167 - 209g
- Fasting period before study: 16 hours
- Housing: collective caging, cage type: Macrolon type IlI./max. 5
- Diet: ad libitum; Ssniff Spezialdiäten GmbH, 4770 Soest/Westfalen
- Water: ad libitum; Macrolon dringking bottles, Becker & Co. 4620 Castrop-Rauxel
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 50 - 80
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours daily, fluorescent light, 120 lux

IN-LIFE DATES:
From: 09.08.1989 To: 24.08.1989

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

20% dispersion

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% dispersion
- Amount of vehicle (if gavage): no data

The test substance wa heated up to about 37°C and diluted with Aqua deion. by using a magnetic stirrer in order to get a 20 % dispersion.
The pH-value was 7.9.

MAXIMUM DOSE VOLUME APPLIED: 2.1 mL

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Range finding study:
Two female rats were employed in a preliminary range finding study. The dosage of the single oral administration was 2000 mg/kg bw. This preliminary study showed no mortalities.

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the body weights were recorded at day 0 (beginning of the experiment), at day 7 and at day 14 (terminal necropsy) on the surviving animals.
- Necropsy of survivors performed: yes
- Clinical signs: the evaluation of the clinical-toxicological signs (a modified Irwin-Screening by Screening methods in pharmacology, R. A. Turner, 1965) was done individually and depends on the nature of the signs. If the symptoms persist to the same degree for a longer period of time, this was noted in the corresponding protocols. Records were made according to the following intervals: approx. 20', 1 h, 2 + 3 h, 6 h, 24 h, thereafter once daily up to day 14.

Observation:
Records were made according to the following intervals: approx. 20', 1 h, 2+3 h, 6 h, 24 h, thereafter once daily up to day 14.

Preliminary study:

Two female rats were employed in a preliminary range finding study. The dosage of the single oral administration was 2000 mg/kg bw. This preliminary study showed no mortalities.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no

Clinical signs:

other: The sampIe induced during the entire observation period of 14 days no clinical-/toxicological symptoms.

Gross pathology:

Necropsies performed on all animals at the end of the 14-day observation period showed no test compound-related macroscopic findings in the cranial-, thoracic- and abdominal cavity.

The LD50 deterrnination showed the following result: 24 h + 14 days, male + female > 2000 mg/kg bw

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008) and DSD (Directive 67/548/EEC)

Conclusions:

The toxicity after a single oral intake of the test sample is above the dose limit 2000 mg/kg bw. The substances does not need to be classified according to CLP, EU GHS (Regulation (EC) No 1272/2008) and according to DSD (Directive 67/548/EEC).

Executive summary:

In an acute oral toxicity study (limit test) performed according to the OECD Guideline 401 (Acute Oral Toxicity), groups of fasted Wistar rats (5/sex)

were given a single oral dose of Sucroglyceride C12-18, C18unsatd. in water at a dose of 2000 mg/kg bw and observed for 14 days.

Oral LD50:

Males > 2000 mg/kg bw

Females > 2000 mg/kg bw

Combined > 2000 mg/kg bw

There were no treatment related clinical signs, necropsy findings or changes in body weight.

Sucroglyceride C12-18, C18unsatd. is practically nontoxic based on the LD50 in males/females. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is a GLP compliant guideline study with Klimisch score 1.
The three supporting studies confirm in all cases the absence of adverse effects, i.e. effect levels for the LD50 are 2000 mg/kg bw. Furthermore, all supporting studies are GLP compliant guideline studies, their Klimisch scores were changed from 1 to 2 to reflect the fact that they were conducted on read-across substances.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2008-08-06 to 2008-08-20

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Guideline study performed on a supporting substance (structural analogue). In accordance with the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines, 2000

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: mean males: 243 g, mean females: 164 g ; variation did not exceed +/- 20 % of the sex mean
- Housing: in a controlled environment, individually housed in Macrolon cages (Mill type, height 18 cm)
- Diet: free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest,Germany)
- Water: ad libitum, tap water
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
- Area of exposure: approx. 10 % of the total body surface, i.e, approx. 25 cm2 for males and 18 cm2 for females.
- % coverage: 10 % of body surface
- Type of wrap if used: dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic
bandage. A piece of Micropore taps was additionally used for fixation of the bandages in females only.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin cleaned of residual test substance using tap water
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (2.02 ml/kg) body weight. Dose volume calculated as dose level (g/kg) / density (g/ml)
- The test substance was dosed undiluted as delivered by the sponsor.

Duration of exposure:

24 h

Doses:

2000 mg/kg (2.02 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / density (g/mL)

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: mortality: twice daily; body weight: days 1 (pre-administration), 8 and 15 and at death; clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

No

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

- One male was found dead on day 2. The death of one male on day 2 after treatment was considered to be spontaneous and not treatment related, no macroscopic abnormalities were found at necropsy.

Clinical signs:

other: - Piloerection was noted in all males and two females on day 1. - Scales were seen in the treated skin-area of two females during the observation period (one female at day 4 and 5, the other at day 15, respectively) .

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008) and DSD (Directive 67/548/EEC)

Conclusions:

The dermal LD50 value of the substance in Wistar rats was established to be > 2000 mg/kg bw. The substances does not need to be classified according to CLP, EU GHS (Regulation (EC) No 1272/2008) and according to DSD (Directive 67/548/EEC).

Executive summary:

In an acute dermal toxicity study according OECD guideline 402, 5 male and 5 female young adult Wistar rats were dermally exposed to Isostearic acid, esters with methyl α-D-glucoside. The test substance was dosed undiluted for 24 hours to 10% of body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 15 days.

Dermal LD₅₀ males/females > 2000 mg/kg bw (limit test)

There were no treatment related clinical signs, necropsy findings or changes in body weight.

The death of one male on day 2 after treatment was considered to be spontaneous and not treatment related, no macroscopic abnormalities were found at necropsy.

The test substance Isostearic acid, esters with methyl α-D-glucoside is practically nontoxic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is a GLP compliant guideline study. Its Klimisch score was changed from 1 to 2 to reflect the fact that it was conducted on a read-across substance.

Additional information

Assessment of acute oral toxicity in the rat

 

Key study on the registration substance Sucroglyceride C12-18, C18unsatd. (Evonik, 1989)

For classification and labelling purposes Sucroglyceride C12-18, C18unsatd. was tested regarding its acute toxic potential following oral application. The substance is a white waxy solid. The study design chosen was a limit test at a dose level of 2000 mg/kg bw.

In an acute oral toxicity study performed according to the OECD Guideline 401 (Acute Oral Toxicity), in an initial preliminary trial 2 female fasted Wistar rats were given a single oral dose of Sucroglyceride C12-18, C18unsatd., formulated as a 20 % dispersion in water, at a dose of 2000 mg/kg bw and no mortalities were reported over a period of 14 days. In the following main experiment 1 group of fasted Wistar rats (5/sex) were treated identically to the animals in thre preliminary trial and were then observed for 14 days. The animals showed a normal weight gain over the observation period, no clinical toxicological symptoms were present and during necropsy, performed on all animals at the end of the 14-day observation period, no test compound-related macroscopic findings were reported for the cranial, thoracic and abdominal cavities.

Thus, the LD50-value for the registration substance Sucroglyceride C12-18, C18unsatd. is higher than 2000 mg/kg bw.

 

Supporting study on the read-across substance Sucroglyceride C12 (Evonik, 1989)

The read-across substance Sucroglyceride C12, a structural analogue of the registration substance, was tested for its acute toxic potential following oral application. The substance is a white waxy solid. The study design chosen was a limit test at a dose level of 2000 mg/kg bw.

The study design and the preparation of the test substance were identical to the key study reported above. No mortalities were reported over a period of 14 days. The body weight gain, the clinical toxicological observations made during the study and the macroscopic observations made at necropsy exhibited no treatment-related effects.

Thus, the LD50-value for the read-across substance Sucroglyceride C12 is higher than 2000 mg/kg bw.

 

Supporting study on the read-across substance Stearic acid, esters with methyl α-D-glucoside (Evonik, 1990)

The read-across substance Stearic acid, esters with methyl α-D-glucoside, a structural analogue of the registration substance, was tested for its acute toxic potential following oral application. The substance is a solid. The study design chosen was a limit test at a dose level of 2000 mg/kg bw.

The study design and the preparation of the test substance was identical to the key study reported above. No mortalities were reported over a period of 14 days and the body weight gain, the clinical toxicological observations made during the study exhibited no treatment-related effects. At necropsy, macroscopic observations were recorded for the lung (lung of one male marbled), the kidney (kidneys of 2 males marbled, of one male deformed with red spot on the surface) and the genital system (2 females with hydrometra in the uterus). These macroscopic changes observed were attributable to the sacrificing procedure or to minor variations which often occur spontaneously in rats of this strain and age and were considered to be spontaneous and not test item dependent.

Thus, the LD50-value for the read-across substance Stearic acid, esters with methyl α-D-glucoside is higher than 2000 mg/kg bw.

 

Supporting study on the read-across substance Isostearic acid, esters with methyl α-D-glucoside (Evonik, 2009)

The read-across substance Isostearic acid, esters with methyl α-D-glucoside, a structural analogue of the registration substance, was tested for its acute toxic potential following oral application. The substance is a yellow paste. The study design chosen was the acute toxic class method.

In an acute oral toxicity study performed according to the OECD Guideline 423 (Acute Oral Toxicity - Acute Toxic Class Method), groups of 3 fasted, young adult female Wistar rats per group were given a single oral dose of test substance Isostearic acid, esters with methyl α-D-glucoside in 1% aq. carboxymethyl cellulose and water. The initial dose was 300 mg/kg bw. Over 15 days of observation no mortalities occurred and the only clinical signs recorded at the initial dose level were hunched posture and/or piloerection in all animals on day 1 and 2. In a stepwise procedure additional groups of females were dosed at 300 and 2000 mg/kg bw. No mortalities occurred and hunched posture and/or piloerection were noted in all animals on day 1. For all animals, the body weight gain was unaffected by treatment and no abnormalities were found at macroscopic post mortem examination performed after terminal sacrifice on day 15.

Thus, the LD50-value for the read-across substance Isostearic acid, esters with methyl α-D-glucoside is higher than 2000 mg/kg bw.

 

 

General evaluation of acute oral toxicity

For acute oral toxicity, the registration substance Sucroglyceride C12-18, C18unsatd. and the three read-across substances Sucroglyceride C12, Stearic acid, esters with methyl α-D-glucoside and Isostearic acid, esters with methyl α-D-glucoside exhibit a comparable toxicological profile and are characterised by experimental results which lead to the same overall evaluation with regard to classification and labelling.

 

For the registration substance Sucroglyceride C12-18, C18unsatd. and for three read-across substances, the toxicity after a single oral intake of the test sample is above the LD50 dose limit of 2000 mg/kg bw.

 

Based on the experimental evidence provided for acute oral toxicity, Sucroglyceride C12-18, C18unsatd. does not need to be classified for acute oral toxicity according to CLP, EU GHS (Regulation (EC) No 1272/2008) and according to DSD (Directive 67/548/EEC) and labelling is not required.

 

 

Assessment of acute dermal toxicity in the rat

 

Key study on the read-across substance Isostearic acid, esters with methyl α-D-glucoside (Evonik, 2009)

For classification and labelling purposes Isostearic acid, esters with methyl α-D-glucoside was tested regarding its acute toxic potential following dermal application. The substance is a yellow paste. The study design chosen was a limit test at a dose level of 2000 mg/kg bw.

In an acute dermal toxicity study performed according to the OECD Guideline 402 (Acute Dermal Toxicity), Isostearic acid, esters with methyl α-D-glucoside was administered undiluted to five Wistar rats of each sex by a single occlusive dermal application at 2000 mg/kg bw for 24 hours. 10% of the body surface were exposed and the observation period after treatment lasted for 15 days.

One male was found dead on day 2. This event was considered to be spontaneous and not treatment related, no macroscopic abnormalities were found at necropsy. Piloerection was noted in all males and two females on day 1. Scales were seen in the treated skin-area of two females during the observation period (one female at day 4 and 5, the other at day 15, respectively). The body weight gain in males and females was not affected by treatment and for all animals in the study at the macroscopic post mortem examination no abnormalities were found.

 

General evaluation of acute dermal toxicity

For the read-across substance Isostearic acid, esters with methyl α-D-glucoside the toxicity after a single dermal treatment is above the LD50 dose limit of 2000 mg/kg bw.

 

The read-across substance Isostearic acid, esters with methyl α-D-glucoside has been shown to be comparable to the registration substance Sucroglyceride C12-18, C18unsatd. for acute oral toxicity.

 

On the basis of this comparability, extrapolating the read-across results for acute dermal toxicity to the registration substance, Sucroglyceride C12-18, C18unsatd. does not need to be classified for acute dermal toxicity according to CLP, EU GHS (Regulation (EC) No 1272/2008) and according to DSD (Directive 67/548/EEC) and labelling is not required.

Justification for selection of acute toxicity – oral endpoint
Only one study on Sucroglyceride C12-18, C18unsatd. is available, the other three studies report read-across data from supporting substances (structural analogues).

Justification for selection of acute toxicity – inhalation endpoint
Sucroglyceride C12-18, C18unsatd. is a waxy solid paste, hence the generation of inhalable particles such as dust or aerosols is not relevant. Furthermore, even though the measurement of the vapour pressure is technically not feasible, it is expected to be low and vapourisation is not likely to occur.
Consequently, inhalation is no relevant route of exposure and testing by inhalation is not appropriate according to REACH-VO Annex VIII 8.5.2 Column 2.

Justification for selection of acute toxicity – dermal endpoint
Only one study available for this endpoint.

Justification for classification or non-classification

For acute oral toxicity, the LD50 is > 2000 mg/kg bw for the test substance and for three chemically closely related substances. Consequently, unambiguous data are available to support that, according to the CLP Regulation (EC) No 1272/2008 and according to DSD (67/548/EEC), there is no need for classification of Sucroglyceride C12 -18, C18unsatd. for acute oral toxicity and no labelling is required.

Furthermore, for acute dermal toxicity in a read-across study with a chemically related substance the LD50 observed was > 2000 mg/kg bw. The read-across approach is considered justified for this endpoint and for the substance tested and, hence, according to the CLP Regulation (EC) No 1272/2008 and according to DSD (67/548/EEC), the registration substance Sucroglyceride C12-18, C18unsatd. does not have to be classified for acute oral toxicity and does not have to be labelled.