Constitutional isomers of penta-O-allyl-β-D-fructofuranosylα-D-glucopyranoside; Constitutional isomers of hexa-O-allyl-β-D-fructofuranosylα-D-glucopyranoside; Constitutional isomers of hepta-O-allyl-β-D-fructofuransoylα-D-glucopyranoside

Endpoint summary

Description of key information

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight.
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

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:

19 May 2014 to 11 June 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

The females were nulliparous and non-pregnant.
Acclimatization period of at least five days.
housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food was allowed throughout the study.
The temperature and relative htunidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

used because the test item did not dissolvc/suspend in distilled wate

Details on oral exposure:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing.

Doses:

Preliminary Test
1 female - 2000 mg/kg (corresponding to 1.82 mL/kg as the gravity of the solution is 1.104)
1 female - 300 mg/kg (corresponding to 10 mL of 3g/mL per kilo)

In the absence of toxicity at 300 mg/kg, an additional group of animals was treated as follows: 300 mg/kg (corresponding to 10 mL of 3g/mL per kilo)

No. of animals per sex per dose:

A total of five females were therefore treated at a dose level of 300 mg/kg in the study.

Control animals:

no

Details on study design:

Clinical observations were made 1/2, 1, 2, and 4 hours after dosing and then daily for up to fourteen days. Morbidity and mortality checks were made twice daily.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavitics. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

No statistics

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg: The animal was found dead 1 day after dosing.
300 mg/kg: There were no deaths.

Clinical signs:

other: 2000 mg/kg: Body tremors were noted 4 hours after dosing. 300 mg/kg: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

2000 mg/kg: Abnormalities noted at necropsy were dark liver, dark kidneys and epithelial sloughing of the gastric mucosa.
300 mg/kg: No abnormalities were noted at necropsy.

DOSE LEVEL 2000 mg/kg

- Individual clinical observations and mortality data are given in Table 1 (attached).

- Body weights on Day 0 and at death are provided in Table 2 (attached).

- Necropsy findings are given in Table 3 (attached).

DOSE LEVEL 300 mg/kg

- Individual clinical observations and mortality data are given in Table 4 (attached).

- Individual body weights and body weight changes are given in Table 5 (attached).

- Individual necropsy changes are given in Table 6 (attached).

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight.

Executive summary:

Introduction

The study was performed to assess the acute oral toxicity ofthe test item in the Wistar strain rat.

Methods

Following a sighting test at dose levels of 2000 mg/kg and 300 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a solution in arachis oil BP, at a dose level of 300 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality. The animal treated at a dose level of 2000 mg/kg was found dead 1 day after dosing. There were no deaths at a dose level of 300 mg/kg.

Clinical Observations. Body tremors were noted in the animal treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity at a dose level of 300 mg/kg.

Body Weight. Surviving animals showed expected gains in body weight.

Necropsy. Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were dark liver, dark kidneys and epithelial sloughing of the gastric mucosa. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.

Conclusion

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

Modern GLP studies following OECD test guidelines, both Klimisch grade 1.

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:

experimental study

Adequacy of study:

key study

Study period:

22 May 2014 to 5 June 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: There were no deviations (unplanned changes) from the study plan.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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:

The females were nulliparous and non-pregnant.
Acclimatization period of at least five days the animals.
At the start of the study the animals weighed at least 200 g, and were eight to twelve weeks of age.
Weight variation did not exceed +/- 20% of the mean weight for each sex.
The animals were housed in suspended solid floor polypropylene cages fiimished with Woodflakes. The animals were housed individually during the 24-Hour exposure period and in groups of five, by sex, for the remainder of the study.
Free access to mains drinking water and food was allowed throughout the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (6:00 to 18:00) and twelve hours darkness

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day before treatment the back and flanks of each animal were clipped free of hair.
Applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe.

Duration of exposure:

24 hours contact

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not required

Details on study design:

The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
After removal of the dressings and subsequently once daily for fotuteen days, the test sites were examined for evidence of primary irritation and scored.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Signs of dermal irritation noted at the test sites of three females were very slight erythema, crust formation, scab cracking, small superficial scattered scabs and glossy skin. There were no signs of dermal irritation noted at the test sites ofall males and two females.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Executive summary:

Introduction

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat.

Methods

A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals Were subjected to gross necropsy.

Results

Mortality. There were no deaths.

Clinical Observations.

There were no signs of systemic toxicity.

Dermal Irritation.

Signs of dermal irritation noted at the test sites of three females were very slight erythema, cnist formation, scab cracking, small superficial scattered scabs and glossy skin. There were no signs of dermal irritation noted at the test sites of all males and two females.

Body Weight.

Animals showed expected gains in body weight, except for one female which showed body weight loss during the first week but expected gain in body weight during the second week.

Necropsy.

No abnormalities were noted at necropsy.

Conclusion

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Modern GLP studies following OECD test guidelines, both Klimisch grade 1.

Additional information

Acute Oral Toxicity Study

The study was performed to assess the acute oral toxicity ofthe test item in the Wistar strain rat.

Following a sighting test at dose levels of 2000 mg/kg and 300 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a solution in arachis oil BP, at a dose level of 300 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. The animal treated at a dose level of 2000 mg/kg was found dead 1 day after dosing. There were no deaths at a dose level of 300 mg/kg.

Clinical Observations. Body tremors were noted in the animal treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity at a dose level of 300 mg/kg.

Body Weight. Surviving animals showed expected gains in body weight.

Necropsy. Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were dark liver, dark kidneys and epithelial sloughing of the gastric mucosa. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight.

Acute Dermal Toxicity Study

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat.

A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals Were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations.

There were no signs of systemic toxicity.

Dermal Irritation.

Signs of dermal irritation noted at the test sites of three females were very slight erythema, cnist formation, scab cracking, small superficial scattered scabs and glossy skin. There were no signs of dermal irritation noted at the test sites of all males and two females.

Body Weight.

Animals showed expected gains in body weight, except for one female which showed body weight loss during the first week but expected gain in body weight during the second week.

Necropsy.

No abnormalities were noted at necropsy.

Conclusion

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.

Acute Inhalation Study

Although balance readings were too low and variable to allow direct measurement at 20 °C, the substance is a viscous liquid with a determined vapour pressure of 0.0024 Pa at 38 °C and exposure of humans via the inhalation route is predicted to be low. Furthermore, it is expected that the most likely route of exposure for workers and consumers is the dermal route, and in accordance with REACH Section 8.5.2 column 2, investigation of acute toxicity via the inhalation route is unnecessary.

Justification for classification or non-classification

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight. No adverse effects in athe acute dermal toxicity study and thus the test item will be classified as Harmful by the acute oral route.