Undecyl glucoside

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 Jun 1988 - 17 Jul 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study with acceptable restriction. No ophthalmological examinations were performed prior to treatment. No information on detailed clinical examinations.

Justification for type of information:

refer to category justification provided in IUCLID section 13

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.26 (Sub-Chronic Oral Toxicity Test: Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

No ophthalmological examinations were performed prior to treatment; no information on detailed clinical examinations

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

D-Glucopyranose, oligomeric, C10-16-alkyl glycosides

EC Number:

600-975-8

Cas Number:

110615-47-9

Molecular formula:

not applicable (UVCB)

IUPAC Name:

D-Glucopyranose, oligomeric, C10-16-alkyl glycosides

Test animals

Species:

rat

Strain:

other: Sprague Dawley CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld; Germany
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 169.6 (m) and 140.9 (f) g (control group); 157.0 (m) and 140.7 (f) g (250 mg/kg bw/d test group); 161.5 (m) and 138.4 (f) g (500 mg/kg bw/d test group); 166.5 (m) and 138.2 (f) g (1000 mg/kg bw/d test group)
- Housing: animals were housed in groups of 2-3 per sex in Makrolon type III cages with soft wood bedding (ARWI-Center, Essen, Germany)
- Diet: pelleted maintenance diet Altromin 1324 DK (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 54-68
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 27.06.1988 To: 29/30.09.1988 (main test groups) and 26.10.1988 (satellite control and test group)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: dosing solutions of the test substance in water were prepared daily and just prior to application.

VEHICLE
- Concentration in vehicle: 2.5, 5 and 10% w/v
- Amount of vehicle (if gavage): 10 mL/kg bw

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

90 days

Frequency of treatment:

once daily in the morning, 5 days/week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

250 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

10 (main study), 5 (satellite control and high dose group)

Control animals:

yes, concurrent vehicle

Details on study design:

- Rationale for selecting satellite groups: satellite groups were used to assess the cumulative toxicity and reversibility of effects.
- Post-exposure recovery period in satellite groups: 27 days

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: animals were checked for mortality and clinical signs twice daily.

BODY WEIGHT: Yes
- Time schedule for examinations: animals were weighed at arrival, on the first day of treatment, and then weekly throughout the treatment period and before necropsy.

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Food consumption for each animal cage determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

WATER CONSUMPTION AND COMPOUND INTAKE: Yes
- Time schedule for examinations: Water consumption was calculated at weekly intervals with the exception of days where clinical examinations were performed.

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: 1 day before necropsy
- Dose groups that were examined: control and high dose group

HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 6 weeks (interim examination) and at study termination
- Anaesthetic used for blood collection: Yes (ether)
- Animals fasted: No data
- How many animals: all surviving animals
- Parameters listed in Table 1 under "Any other information on materials and methods incl. tables" were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: : after 6 weeks (interim examination) and at study termination
- Animals fasted: No data
- How many animals: all surviving animals
- Parameters listed in Table 1 under "Any other information on materials and methods incl. tables" were examined.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see Table 2 under "Any other information on materials and methods incl. tables)"

HISTOPATHOLOGY: Yes (see Table 2 under "Any other information on materials and methods incl. tables)"

ORGAN WEIGHTS: Yes (see Table 2 under "Any other information on materials and methods incl. tables)"

Necropsy included the examination of all major organs, tissues and body cavities. Histopathological examinations were performed on all the animals of the control and high dose groups. The histopathological examination of the glandular stomach was also performed in animals of the intermediate dose groups and the satellite high dose group.

Statistics:

The following statistical analyses were performed to compare mean values of control and treatment groups:
- t-test: body weights and blood parameters
- t-test followed by Dunnett’s test: biochemical parameters
- U-test: organ weights

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

250 mg/kg bw/d (males): slightly reduced body weights until Week 5 and in Week 7; 500 mg/kg bw/d (males): slightly reduced body weights between Weeks 1-7

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Description (incidence and severity):

1000 mg/kg bw/d: slightly increased

Ophthalmological findings:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

1000 mg/kg bw/d: edema and ulceration of the forestomach

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

500 and 1000 mg/kg bw/d: inflammatory edema of the submucosa of the forestomach as well as multiple ulcerations; acanthosis and proliferation of forestomach mucosa; 1000 mg/kg bw/d (satellite group): incomplete regeneration of forestomach mucosa

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
No substance-related mortalities occurred during the study period. Due to mistakes in blood sampling, two males of the group 2 (250 mg/kg bw/d) inadvertently died. One female of group 3 (500 mg/kg bw/day) died as a result of incidental gavage errors.

BODY WEIGHT AND WEIGHT GAIN
The total body weight gain was slightly decreased during Weeks 1-7 of applications in males of groups 2 (250 mg/kg bw/d) and 3 (500 mg/kg bw/d) in comparison to control due to lower initial weight of the above test groups.

FOOD CONSUMPTION AND COMPOUND INTAKE
No substance-related effects on food consumption were observed during the study period.

WATER CONSUMPTION AND COMPOUND INTAKE
During test substance administration, the mean water intake was, probably compound related, slightly increased in test animals of the group 4 (1000 mg/kg bw/d).

OPHTHALMOSCOPIC EXAMINATION
There were no treatment-related changes at the ophthalmological examination.

HAEMATOLOGY
No substance-related effects were observed for haematological parameters at study termination. Slight changes in leukocytes, lymphocytes and thrombocytes were observed at the interim examination (after 6 weeks).

CLINICAL CHEMISTRY
No substance-related changes in clinical chemistry parameters were noted during the study.

ORGAN WEIGHTS
Although a slight reduction in the absolute organ weights of gonads, brain and thymus as well as slight increases in the relative organ weights of kidney and liver occurred in the treated groups, these effects were not considered to be treatment-related since no corresponding changes in histopathology were observed.

GROSS PATHOLOGY
Gross section revealed ulcerations and oedema restricted to forestomach in the group 4 (1000 mg/kg bw/d).

HISTOPATHOLOGY: NON-NEOPLASTIC
Histopathogical evaluation revealed inflammatory edema of the submucosa as well as multiple ulcerations associated with acanthosis and proliferation of the mucous membrane of forestomach in animals of groups 3 (500 mg/kg bw/d) and 4 (1000 mg/kg bw/d), but less distinctive in group 3. The test animals of group 2 (250 mg/kg bw/d) did not show substance-related findings in the forestomach. Animals of the 1000 mg/kg bw/d satellite group demonstrated incomplete regeneration of the forestomach mucosa after 27 treatment-free days.

Effect levels

1

Key result

Dose descriptor:

LOEL

Remarks:

local

Effect level:

500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: inflammation and ulcerations of mucous membrane of the forestomach due to bolus administration and irritating potential of the test substance (local effect)

2

Key result

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no systemic or cumulative effects

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

A 90-day repeated dose toxicity study with the test material was performed equivalent to EU Method B.26 and GLP. Administration of the test material up to and including the highest dose tested (1000 mg/kg bw/day) did not results in any substance-related adverse effects. Thus, a NOAEL ≥1000 mg/kg bw/day was derived.