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

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

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 is cited by CIR, 2011. Decyl Glucoside and Other Alkyl Glucosides as Used in Cosemtics. 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:

Ecology and Toxicology of Alkyl Polyglucosides

Author:

Willing A, Messinger H and Aulmann W

Year:

2004

Bibliographic source:

CIR, 2011. Decyl Glucoside and Other Alkyl Glucosides as Used in Cosemtics. Final Safety Assessment.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

C12/16 Alkyl Polyglucoside

IUPAC Name:

C12/16 Alkyl Polyglucoside

Test material form:

not specified

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Main experiment: 10 males and 10 females.
Control: 5 males and 5 females.

Administration / exposure

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

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
250 mg/kg bw/day
Basis:
no data

Doses / concentrations 2

Remarks:

Doses / Concentrations:
500 mg/kg bw/day
Basis:
no data

Doses / concentrations 3

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

Examinations

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.

Results and discussion

Results of examinations

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

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: irritation and ulcers in the forestomach

2

Key result

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

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

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.