Esterification products of C10-14 (even numbered) alkyl oligomeric glycosides with citric acid, disodium salts

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

other: ReadAcross

Remarks:

The end point is covered by test carried out on another AlkylPolyGlucoside esters considering the similar structure and a number of cross experiments which shown a similar behaviour. A rationale is available on it

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study cited by: CIR, 2011. Decyl Glucoside and Other Alkyl Glucosides as Used in Cosmetics. Final Safety Assessment.

Justification for type of information:

The end point is covered by test carried out on another AlkylPolyGlucoside esters considering the similar structure and a number of cross experiments which shown a similar behaviour. A rationale is available on it

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

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 disodium 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 " Sodium salt of esterification products of C10-C16 (even numbered) alkylpolyglycosides with citric acid" through the inhalation route was considered not significant.

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.

Endpoint conclusion:

no study available

Endpoint conclusion:

no study available

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

180 mg/kg bw/day

Study duration:

subacute

Species:

rabbit

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEL

1.18 mg/cm²

Study duration:

subacute

Species:

rabbit

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 disodium 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 disodium 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 disodium sulfite" pertains to this group.

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""Sodium salt of esterification products of C10-C16 (even numbered) alkylpolyglycosides with citric acid"  for acute effects. Indeed skin irritation resulted to be slight like the irritation of mucose membrane, as for acute eye exposure.

Results of repeated toxicity studies did not lead to the classification of ""Sodium salt of  esterification products of C10-C16 (even numbered) alkylpolyglycosides with citric acid" for long term effects.

 

Specific Target Organ Toxicity after Repeated Exposure:

Classification: not required

Signal word: none

Hazard statement: none

Data source

Reference

Reference Type:

secondary source

Title:

Unnamed

Year:

1992

Materials and methods

Test guideline

Qualifier:

no guideline available

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

Test material

Test material information

Constituent 1

Reference substance name:

caprylyl/capryl glucoside

IUPAC Name:

caprylyl/capryl glucoside

Test material form:

not specified

Test animals

Species:

rabbit

Strain:

not specified

Sex:

male

Administration / exposure

Type of coverage:

other: non-occlusive

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 days

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
60 mg/kg bw/day
Basis:
nominal per unit area

Doses / concentrations 2

Remarks:

Doses / Concentrations:
180 mg/kg bw/day
Basis:
nominal per unit area

Doses / concentrations 3

Remarks:

Doses / Concentrations:
540 mg/kg bw/day
Basis:
nominal per unit area

No. of animals per sex per dose:

6 males per group

Results and discussion

Results of examinations

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.

Effect levels

1

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.

2

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.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

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.