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Administrative data

Description of key information

Available literature data regarding the group of alkyl polyglucosides permitted to evaluate the long-term effects produced by "Sulfonation products of (esterification products of C9-11 (branched and linear) alkyl-(mono-, di- and tri-) glycosides with maleic anhydride) with dipotassium sulfite". More in details, an oral subchronic repeated toxicity study, an oral combined repeated dose toxicity study with reproduction/developmental toxicity screening test and a dermal subacute repeated toxicity study were available and permitted to use the effect level values in the derivation of the no-effect levels (see DNEL Section). No inhalation repeated toxicity study is available because the exposure to "Sulfonation products of (esterification products of C9-11 (branched and linear) alkyl-(mono-, di- and tri-) glycosides with maleic anhydride) with dipotassium sulfite" through the inhalation route was considered not significant.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

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Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study is cited by CIR, 2011. Decyl Glucoside and Other Alkyl Glucosides as Used in Cosemtics. Final Safety Assessment.
Qualifier:
according to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
Deviations:
not specified
GLP compliance:
not specified
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Main experiment: 10 males and 10 females.
Control: 5 males and 5 females.
Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
Daily
Remarks:
Doses / Concentrations:
250 mg/kg bw/day
Basis:
no data
Remarks:
Doses / Concentrations:
500 mg/kg bw/day
Basis:
no data
Remarks:
Doses / Concentrations:
1000 mg/kg bw/day
Basis:
no data
No. of animals per sex per dose:
Main experiment: 10 males and 10 females.
Control: 5 males and 5 females.
Control animals:
yes
Observations and examinations performed and frequency:
Animal were subjected to routine clinical observations. Their body weight and food and water consumption were recorded. Haematologicalm clinicochemical and ophtalmoscopic investigations were performedduring week 7 and 13. At the end of the treatment period, all the animals were subjected to general pathological examination and organ weight analizes. A wide range of tissues was fixed and examineted by microscope.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
2 mortalities.
Mortality:
mortality observed, treatment-related
Description (incidence):
2 mortalities.
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
ulcers and oedema confined to the forestomach of the highest dose level.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
slowly reversible, dose-related irritation and ulceration of the mucous membrane of the forestomach of animals in the highest dose group.
Histopathological findings: neoplastic:
not specified
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Dose descriptor:
other: NOAEC
Effect level:
2.5 other: %
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: irritation and ulcers in the forestomach
Critical effects observed:
not specified
Conclusions:
Systemic toxicity was not observed in any group. The NOAEL for systemic toxicity was 1000 mg/kg bw/day. The NOEC for “local compatibility” (irritation and ulceration of the mucous membrane of the forestomach) was deduced as 2.5% active ingredient.
Executive summary:

Sprague-Dawley rats were dosed by gavage with 0, 250, 500 and 1000 mg/kg bw/day C12/16 APG for 90 days. An additional 5 male and 5 female control and high dose rats were used as a recovery group. There were two fatalities, neither of which was linked to the test material. No treatment-related changes in body weights, organ weights, or biochemistry or hematology parameters were observed. Absolute gonad weights were decreased in all test groups, but the decrease was not considered treatment related by the researchers because of a lack of a dose-response. A dose-dependent, slowly reversible, irritation and ulceration of the forestomach mucosa was observed in animals of the 0.5 and 1 g/kg bw groups. Systemic toxicity was not observed in any group. The NOAEL for systemic toxicity was 1000 mg/kg bw. The NOEC for “local compatibility” (irritation and ulceration of the mucous membrane of the forestomach) was deduced as 2.5% active ingredient.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The combined repeated dose toxicity study with reproduction/developmental toxicity screening test confirms the results of the read-across study.

Repeated dose toxicity: inhalation - systemic effects

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Reference
Endpoint:
repeated dose toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

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Reference
Endpoint:
repeated dose toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
other:
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

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Reference
Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study cited by: CIR, 2011. Decyl Glucoside and Other Alkyl Glucosides as Used in Cosmetics. Final Safety Assessment.
Qualifier:
no guideline available
Deviations:
not applicable
Principles of method if other than guideline:
Using non-occlusive applications, 2 mL of 0, 0.06, 0.18, or 0.54 g a.i./kg caprylyl/capryl glucoside (60% active) in distilled water (corresponding to concentrations of 0, 3, 9, and 27% a.i., respectively) were applied to the intact skin of the backs of 6 male rabbits/group.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Sex:
male
Type of coverage:
other: non-occlusive
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
14 days
Remarks:
Doses / Concentrations:
60 mg/kg bw/day
Basis:
nominal per unit area
Remarks:
Doses / Concentrations:
180 mg/kg bw/day
Basis:
nominal per unit area
Remarks:
Doses / Concentrations:
540 mg/kg bw/day
Basis:
nominal per unit area
No. of animals per sex per dose:
6 males per group
Clinical signs:
not specified
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
slight to moderate
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
decrease
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
not statistically significative decrease in testes weight
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
epithelial hyperplasia, hyperkeratosis, congestion, and eschar formation were observed in the skin of rabbits of the high dose group. No test article-related microscopic changes were observed in the testes or accessory sex glands at any dose.
Dose descriptor:
NOAEL
Effect level:
180 mg/kg bw/day
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: Decrease in body and testes weight, not statistically significative.
Dose descriptor:
LOAEL
Effect level:
60 mg/kg bw/day
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: Slight to moderate dermal irritation.
Critical effects observed:
not specified
Conclusions:
In the main study, treatment-related signs of toxicity were not observed. Slight dermal irritation was observed in all groups after the initiation of dosing; the irritation became moderate in the high dose group after 3 days of dosing. Microscopically, epithelial hyperplasia, hyperkeratosis, congestion, and eschar formation were observed in the skin of rabbits of the high dose group; these changes were not observed in rabbits of the other test groups. Body weights of rabbits of the high dose group were slightly, but significantly, decreased compared to controls. Absolute testes weights were slightly, but not significantly, decreased in the high dose group. Microscopically, no test article-related microscopic changes were observed in the testes or accessory sex glands at any dose. No treatment-related effects on hematology or clinical chemistry values or organ weights were reported. The NOEL for systemic toxicity was 0.18 g a.i./kg caprylyl/capryl glucoside.
Executive summary:

In a 14 -day study, using non-occlusive applications, 2 mL of 0, 60, 180, or 540 g active ingredient/kg caprylyl/capryl

glucoside (60% active) in distilled water were applied to the intact skin of the backs of 6 male rabbits/group. Slight dermal irritation was observed in all groups after the initiation of dosing; the irritation became moderate in the high dose group after 3 days of dosing. Microscopically, epithelial hyperplasia, hyperkeratosis, congestion, and eschar formation were observed in the skin of rabbits of the high dose group; these changes were not observed in rabbits of the other test groups. Body weights of rabbits of the high dose group were slightly, but significantly, decreased compared to controls. Absolute testes weights were slightly, but not significantly, decreased in the high dose group. Microscopically, no test article-related changes were observed in the testes or accessory sex glands at any dose.

No treatment-related effects on hematology or clinical chemistry values or organ weights were reported. The NOEL for systemic toxicity was 0.18 g a.i./kg caprylyl/capryl glucoside.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
180 mg/kg bw/day
Study duration:
subacute
Species:
rabbit

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study cited by: CIR, 2011. Decyl Glucoside and Other Alkyl Glucosides as Used in Cosmetics. Final Safety Assessment.
Qualifier:
no guideline available
Deviations:
not applicable
Principles of method if other than guideline:
Using non-occlusive applications, 2 mL of 0, 0.06, 0.18, or 0.54 g a.i./kg caprylyl/capryl glucoside (60% active) in distilled water (corresponding to concentrations of 0, 3, 9, and 27% a.i., respectively) were applied to the intact skin of the backs of 6 male rabbits/group.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Sex:
male
Type of coverage:
other: non-occlusive
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
14 days
Remarks:
Doses / Concentrations:
60 mg/kg bw/day
Basis:
nominal per unit area
Remarks:
Doses / Concentrations:
180 mg/kg bw/day
Basis:
nominal per unit area
Remarks:
Doses / Concentrations:
540 mg/kg bw/day
Basis:
nominal per unit area
No. of animals per sex per dose:
6 males per group
Clinical signs:
not specified
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
slight to moderate
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
decrease
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
not statistically significative decrease in testes weight
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
epithelial hyperplasia, hyperkeratosis, congestion, and eschar formation were observed in the skin of rabbits of the high dose group. No test article-related microscopic changes were observed in the testes or accessory sex glands at any dose.
Dose descriptor:
NOAEL
Effect level:
180 mg/kg bw/day
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: Decrease in body and testes weight, not statistically significative.
Dose descriptor:
LOAEL
Effect level:
60 mg/kg bw/day
Based on:
act. ingr.
Sex:
male
Basis for effect level:
other: Slight to moderate dermal irritation.
Critical effects observed:
not specified
Conclusions:
In the main study, treatment-related signs of toxicity were not observed. Slight dermal irritation was observed in all groups after the initiation of dosing; the irritation became moderate in the high dose group after 3 days of dosing. Microscopically, epithelial hyperplasia, hyperkeratosis, congestion, and eschar formation were observed in the skin of rabbits of the high dose group; these changes were not observed in rabbits of the other test groups. Body weights of rabbits of the high dose group were slightly, but significantly, decreased compared to controls. Absolute testes weights were slightly, but not significantly, decreased in the high dose group. Microscopically, no test article-related microscopic changes were observed in the testes or accessory sex glands at any dose. No treatment-related effects on hematology or clinical chemistry values or organ weights were reported. The NOEL for systemic toxicity was 0.18 g a.i./kg caprylyl/capryl glucoside.
Executive summary:

In a 14 -day study, using non-occlusive applications, 2 mL of 0, 60, 180, or 540 g active ingredient/kg caprylyl/capryl

glucoside (60% active) in distilled water were applied to the intact skin of the backs of 6 male rabbits/group. Slight dermal irritation was observed in all groups after the initiation of dosing; the irritation became moderate in the high dose group after 3 days of dosing. Microscopically, epithelial hyperplasia, hyperkeratosis, congestion, and eschar formation were observed in the skin of rabbits of the high dose group; these changes were not observed in rabbits of the other test groups. Body weights of rabbits of the high dose group were slightly, but significantly, decreased compared to controls. Absolute testes weights were slightly, but not significantly, decreased in the high dose group. Microscopically, no test article-related changes were observed in the testes or accessory sex glands at any dose.

No treatment-related effects on hematology or clinical chemistry values or organ weights were reported. The NOEL for systemic toxicity was 0.18 g a.i./kg caprylyl/capryl glucoside.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
1.18 mg/cm²
Study duration:
subacute
Species:
rabbit

Additional information

In the oral repeated toxicity studies, no systemic effects were observed after the administration of the substance, therefore the NOAEL was set at the highest dose tested (1000 mg/kg bw/day). Locally, instead, oedema and ulceration of the forestomach were noted in the highest dose group.

In the dermal repeated toxicity study, no significative systemic effects were observed, with the exception of a slight decrease in body weights. The NOAEL for systemic toxicity was set at 180 mg/kg bw/day. Locally, instead, slight dermal irritation was noted in all dosage groups, but it became moderate in the highest dose-group after 3 days treatment. The LOAEL for local effects was evaluated to be 60 mg/kg bw/day (1.18 mg/cm3).


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The study refers to the category of alkyl polyglucosides, and "Sulfonation products of (esterification products of C9-11 (branched and linear) alkyl-(mono-, di- and tri-)glycosides with maleic anhydride) with dipotassium sulfite" pertains to this group.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
The study refers to the category of alkyl polyglucosides, and "Sulfonation products of (esterification products of C9-11 (branched and linear) alkyl-(mono-, di- and tri-)glycosides with maleic anhydride) with dipotassium sulfite" pertains to this group.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
The study refers to the category of alkyl polyglucosides, "Sulfonation products of (esterification products of C9-11 (branched and linear) alkyl-(mono-, di- and tri-)glycosides with maleic anhydride) with dipotassium sulfite" pertains to this group.

Justification for classification or non-classification

No severe systemic effects were observed, neither in the oral repeated toxicity study, nor in the dermal repeated toxicity study.

Local effects produced by group of alkyl polyglucosides were coherent with the classification of "Sulfonation products of (esterification products of C9-11 (branched and linear) alkyl-(mono-, di- and tri-)glycosides with maleic anhydride) with dipotassium sulfite" for acute effects. Indeed skin irritation resulted to be slight, while irritation of mucose membrane produced slowly reversible effects, as for acute eye exposure.

Results of repeated toxicity studies did not lead to the classification of "Sulfonation products of (esterification products of C9-11 (branched and linear) alkyl-(mono-, di- and tri-)glycosides with maleic anhydride) with dipotassium sulfite" for long term effects.

Specific Target Organ Toxicity after Repeated Exposure:

Classification: not required

Signal word: none

Hazard statement: none