L-gluco-Octitol, 1,5-anhydro-6,8-dideoxy-, (7.xi.)-

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 September - 04 December 2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Principles of method if other than guideline:

In this GLP study, a group of 10 guinea pigs (5/sex) applied with the test material (0.05 mL), once daily for 14 days and each animal was observed for mortality, clinical signs, body weight change and irritation scores.

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

other: liquid

Details on test material:

- Name of test material: Mexoryl SBB
- Physical state: slightly yellowish liquid
- Lot/batch No.: 0137810
- Date of receipt: 29 August 2008
- Storage condition of test material: Stored at room temperature
- Expiry date: June 2009

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, L'Arbresle, France
- Age at study initiation: 1-2 months
- Weight at study initiation: Males: 355 ± 13 g; females: 363 ± 16 g
- Housing: Housed individually in polycarbonate cages
- Diet: 106 pelleted diet (UAR, Epinay-sur-Orge, France), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 μm), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 50 ± 20 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: Right and left flanks; 2 cm X 2 cm
- Time intervals for shavings or clipplings: Application sites were clipped and shaved on Days -1 (a day before the first treatment), 4, 8, 11 and 14, at least 6 h after treatment (4 h during week-end).
- Undiluted test material was applied once daily to the shaved area of left flank of each animal and the test site was not covered by a dressing. Right flank received applications of purified water under the same experimental conditions.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No rinsing was performed.

TEST MATERIAL
- Amount(s) applied (volume with unit): 0.05 mL
- Constant volume used: Yes

USE OF RESTRAINERS FOR PREVENTING INGESTION: No

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Not applicable

Duration of treatment / exposure:

14 days

Frequency of treatment:

Once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
Undiluted (0.05 mL)
Basis:
other: per application site (2 cm X 2 cm)

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

None

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CLINICAL OBSERVATIONS & MORTALITY: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Days -1, 1, 8 and 15

DERMAL IRRITATION (if dermal study): Yes
- Cutaneous reactions were evaluated on both flanks of each animal daily before treatment and on Day 15 according to OECD Guideline 404.
- Daily Irritation Indices (DI) were calculated for both flanks by adding up the obtained values for erythema and edema in all the animals and dividing this total by the number of animals.
- Weekly Mean Irritation Indices (WI) were obtained by calculating the weekly average of the daily indices.

Sacrifice and pathology:

GROSS PATHOLOGY: No; all the animals were sacrificed by an intraperitoneal injection of sodium pentobarbital and no macroscopic post-mortem examination was performed.
HISTOPATHOLOGY: No; skin samples from both flanks of all animals were fixed in 10 % buffered formalin and no histological examination was performed.

Other examinations:

None

Statistics:

None

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

no effects observed

Description (incidence and severity):

minimal skin irritation

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
- No mortality and no clinical signs of toxicity were recorded during the study.

BODY WEIGHT AND WEIGHT GAIN
- Body weight gains of treated animals were similar to expected values for animals of this strain and age.

CUTANEOUS TOLERANCE
- A very slight erythema was observed on Day 3, on the left flank (treated with the test item) of 1/5 females.
- In almost all the animals, a beige coloration of the skin was observed on the left flank (treated with the test item), from Days 3 or 4 until the end of the observation period (Day 15).
- No cutaneous reactions were observed on the control right flank (purified water).
- Maximum Weekly Mean Irritation Index: 0.014 (Week 1) for the flank treated with the test item and 0.00 for the control flank (purified water)

Effect levels

Dose descriptor:

NOAEL

Effect level:

100 other: %

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects on clinical signs; mortality; body weight and cutaneous reactions

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Under the test conditions, the No Observed Adverse Effect Level (NOAEL) of Mexoryl SBB could be considered as 100 % in Hartley guinea pigs. It is classified as practically non-irritant.

Executive summary:

In a repeated dose dermal toxicity study conducted in compliance with GLP, a group of 10 Hartley Crl: (HA) BR guinea pigs (5/sex) was dermally exposed to 0.05 mL of undiluted Mexoryl SBB, once a day for 14 days consecutively. Undiluted test material was applied once daily to the shaved area of left flank of each animal and the test site was not covered by a dressing. Right flank (control) received applications of purified water under the same experimental conditions. Examinations during the study included: mortality, clinical observation of animals, body weight change and evaluation of cutaneous tolerance.

No mortality and no clinical signs of toxicity were recorded during the study. Body weight gains of treated animals were similar to expected values for animals of this strain and age. A very slight erythema (grade 1) was observed on Day 3, on the left flank (treated with the test item) of 1/5 females. In almost all the animals, a beige coloration of the skin was observed on the left flank (treated with the test item), from Days 3 or 4 until the end of the observation period (Day 15). No cutaneous reactions were observed on the control right flank (purified water). Maximum Weekly Mean Irritation Indexes were 0.014 (Week 1) for the flank treated with the test item and 0.00 for the control flank (purified water)

Under the test conditions, a No Observed Adverse Effect Level (NOAEL) of Mexoryl SBB was not determined. It is classified as practically non-irritant.