D-Glucopyranose, oligomeric, heptyl glycosides

Endpoint summary

Description of key information

Oral (OECD 423), rat (f): LD50 (cut-off) > 5000 mg/kg bw (limit test)
Dermal (OECD 402), rat (m/f): LD50 > 2000 mg/kg bw (limit test), based on read-across

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:

20 May - 04 Jun 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted in 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

adopted in 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Groupe interministeriel des produits chimiques, Ivry sur Seine, France

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Sprague Dawley-SPF Caw

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Janvier Labs, Le Genest St. Isle, France
- Age at study initiation: eight weeks
- Weight at study initiation: 195.2 (mean)
- Fasting period before study: from Day -1 to 4 h after the test administration
- Housing: in groups of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid; sawdust bedding.
- Diet (e.g. ad libitum): foodstuff (Safe, A04), ad libitum (except during the fasting period)
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30- 70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: in the first and second step of the study, 2.0029 g and 2.0001 g of the test item was weighed and distilled water was added to two 10 mL volumetric flask, respectively. Preparations were magnetically stirred to obtain a yellow solution just before the administration.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (females)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were weighed on day 0 (just before administration), on day 2, 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423 may be considered higher than 5000 mg/kg bw.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

2000 mg/kg bw: a thinning of the forestomach was noted in two animals (2/6) during the macroscopic examination of the animals at the end of the study. This finding is not unusual in this type of study and is not considered a major sign of systemic toxicity.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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 based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP guideline study tested with the source substance D-Glucopyranose, oligomers, decyl octyl glycosides (CAS 68515-73-1). According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (Dec 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Clerco Research Farm
- Weight at study initiation: 2536-2979 g (males), 2528-2847 g (females)
- Housing: individually in wire mesh suspension cages
- Diet: Purina Laboratory Rabbit Chow, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Type of wrap if used: the test material was introduced into the sleeve of a rubber dental dam, which was wrapped around the trunk and secured with staples. An outer layer of gauze was placed on the trunk and fixed with tapes.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for gross signs of systemic toxicity once on the day of treatment and then twice during the 14-day observation period. Body weights were determined on the day of treatment (Day 0), and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal irritation, histopathology of unscheduled death

Statistics:

Mean values and standard deviations of body weights were calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One female died during the observation period (on Day 13).

Clinical signs:

other: Clinical changes associated with the test material were as follows: 1. Faecal stains 2. Yellow area throughout the site 3. Emaciated (2 animals) 4. Nasal discharge (3 animals) 5. Lacrimation (1 animal)

Gross pathology:

A gross necropsy performed on the animal which died revealed the following:
1. Faecal stains
2. Discharge from the nose and mouth
3. Lungs appeared reddened
4. Spleen appeared darkened
5. Stomach appeared white
6. Liver covered with an excessive amount of white spots

In 5 of 9 surviving animals, a spotty area of haemorrhage was observed on the lungs at necropsy.

Other findings:

- Histopathology: microscopic examination of the animal which died on Day 13 confirmed the Tyzzer's disease as cause of death.
- Other observations: the most frequently observed irritative effects were as follows:
1. mild to marked erythema
2. mild to moderate oedema
3. mild to moderate atopy
4. mild to moderate desquamation
5. mild coriaceousness

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties.

Additional information

There are no data available on the acute dermal toxicity of D-Glucopyranose, oligomeric, heptyl glycoside. In order to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from a structurally related substance is conducted following a category approach.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13).

Oral

One acute oral toxicity study in rats is available for D-Glucopyranose, oligomeric, heptyl glycoside. In this GLP-study, six female Sprague Dawley rats were exposed via gavage to a limit dose of 2000 mg/kg bw in a stepwise procedure (three rats per step) according to OECD guideline 423 (Richeux, 2014). No mortality and no adverse effects were observed up to the end of the 14-day observation period. With regard to the gross pathology a thinning of the forestomach was noted in two out of six animals during the macroscopic examination of the animals at the end of the study. This finding is not unusual in this type of study and is not considered a major sign of systemic toxicity. Based on the results, the oral LD50 value for female rats was greater than 2000 mg/kg bw. In accordance with OECD guideline 423, the oral LD50 cut-off of the test substance may be considered to be higher than 5000 mg/kg bw.

Dermal

No data are available on the acute dermal toxicity of D-Glucopyranose, oligomeric, heptyl glycoside, but one reliable study of the structurally related category member D-Glucopyranose, oligomers, decyl octyl glycosides (CAS: 68515-73-1), according to OECD guideline 402 and in compliance with GLP, exists, which is used for read-across based on the category approach.

In the acute dermal toxicity study with the category member D-Glucopyranose, oligomers, decyl octyl glycosides, no substance-related mortalities were observed after dermal application of the test substance at a limit dose of 2000 mg/kg bw in male and female New Zealand White rabbits. Test substance-related clinical changes of emaciation (2/5), nasal discharge (3/5), faecal stains (5/5), yellow area throughout the site of application (5/5) and lacrimation (1/5) occurred in the animals. Irritative effects on the skin in the form of moderate to marked erythema, mild to moderate edema, atonia, desquamation, and mild coriaceousness were most frequently observed within the animals. Based on the result of this study, the dermal LD50 value of the test substance for male and female rabbits was greater than 2000 mg/kg bw (Hill Top Biolabs, 1987).

Inhalation

This information is not available. As the test substance has a low vapour pressure and is marketed in aqueous formulation exposure to vapours or dusts is not to be expected. In addition, aerosol application is excluded by the registrant. Furthermore, reliable data from studies for acute toxicity via the oral route with the substance itself and for acute toxicity via the dermal route performed with a structurally related substance according to Regulation (EC) No. 1907/2006, Annex XI, article 1.5 are available.

Justification for selection of acute toxicity – oral endpoint
There is only one study available.

Justification for selection of acute toxicity – inhalation endpoint
No study required since the substance has a low vapour pressure and is marketed as aqueous solution. The dry substance occurs in granules of a size excluding the possibility of inhalation or as solid block; experience demonstrates that no dust formation occurs upon handling. Therefore, human exposure to vapours or dusts is not to be expected, and aerosol applications are excluded by the registrant.

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across based on a category approach. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on the acute toxicity of D-Glucopyranose, oligomeric, heptyl glycoside and a structurally related substance according to Regulation (EC) No 1907/2006, Annex XI, 1.5 do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC; therefore, D-Glucopyranose, oligomeric, heptyl glycoside does not meet the criteria for classification, either, and the data are thus conclusive but not sufficient for classification.