Reaction product of D-Glucopyranoside, methyl; esterified with octadecanoic acid, methyl ester

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 January 2015 to 20 January 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Confidential

IUPAC Name:

Confidential

Test material form:

liquid: viscous

Details on test material:

- Appearance/physical state: Clear, light brown, viscous liquid
- Storage conditions: 18 °C to 24 °C protected from light

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST SYSTEM, ANIMAL RECEIPT AND ACCLIMATION
- Crl:CD(SD) rats from Charles River Laboratories, Inc., Raleigh, NC were used as the test system on this study. The animal model, the Crl:CD(SD) albino rat, is generally recognised as appropriate for acute dermal toxicity studies. The number of animalssselected was the minimum required to satisfy regulatory guidelines. The experimentalsdesign used the procedures and standards required by the current federal and internationalstest guidelines.
- The albino rats utilized for this study were received in good health from Charles River Laboratories, Inc., Raleigh, NC, on 30 December 2014 The rats were inspected by a qualified technician upon receipt, weighed, and uniquely identified by a subcutaneous microchip (BMDS) implanted in the dorso-scapular area. The rats were acclimated to laboratory conditions for a minimum of 5 days. During this period, each animal was observed twice daily for mortality and changes in general appearance or behaviour.

ANIMAL HOUSING
- Upon arrival, all animals were housed individually in clean, stainless steel, wire-mesh cages suspended above cage-board. The animals were maintained by the animal husbandry staff of WIL Research in accordance with SOPs. The animal facilities at WIL Research are accredited by AAALAC International.
- Enrichment devices were provided to all animals as appropriate throughout the study for environmental enrichment and to aid in maintaining oral health of the animals, and were sanitised weekly.

DIET, DRINKING WATER AND MAINTENANCE
- The basal diet used in this study, PMI Nutrition International, LLC, Certified Rodent LabDiet 5002, was a certified feed with appropriate analyses performed by the manufacturer and provided to WIL Research.
- Municipal water supplying the facility was analysed for contaminants according to WIL Research SOPs. The results of the diet and water analyses are maintained at Charles River.
- No contaminants were present in animal feed or water at concentrations sufficient to interfere with the objectives of this study.
- The basal diet and municipal water, delivered by an automatic watering system, were provided ad libitum throughout the acclimation period and during the study.

ENVIRONMENTAL CONDITIONS
- All animals were housed throughout the acclimation period and during the study in an environmentally controlled room. The room temperature and humidity controls were set to maintain environmental conditions of 71 ± 5 °F (22 ± 3 °C) and 50 ± 20 %, respectively.
- Room temperature and relative humidity data were monitored continuously and were scheduled for automatic collection on an hourly basis. Actual mean daily temperature ranged from 70.4 °F to 70.5 °F (21.3 °C to 21.4 °C) and mean daily relative humidity ranged from 32.0 % to 43.0 % during
the study.
- Fluorescent lighting provided illumination for a 12-hour light (0600 hours to 1800 hours) and 12-hour dark photoperiod. Lighting conditions were recorded every 15 minutes.
- Air handling units were set to provide a minimum of 10 fresh air changes per hour.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

PREPARATION
- Prior to use, the bulk test substance container was inverted and/or swirled.
- A sufficient amount of test substance was transferred into a storage container for dispensation.

ASSIGNMENT OF ANIMALS TO TREATMENT GROUPS
- Animals used in the study were randomly selected based on health and body weight from available stock and assigned to groups by use of WTDMS.
- The selected animals were approximately 9 weeks old at initiation of dosing; body weight values ranged from 295 g to 302 g for males and from 200 g to 215 g for females (± 20 % of the mean for each sex).

TEST SUBSTANCE ADMINISTRATION
- One group of 5 male and 5 female rats were dermally administered a single dose (24-hour, semi-occluded exposure) at a dose level of 2000 mg/kg (limit dose).
- The test substance was dosed undiluted based on its specific gravity. The dose volume was determined by dividing the dose levels, expressed as g/kg, by the density (0.98 g/mL, as provided by the safety data sheet). Individual doses were calculated based on body weights taken just prior to dosing and a dose volume of 2.04 mL/kg.
- On the day prior to dosing, the hair was removed from the backs and flanks of the rats using a small animal clipper. Individual doses of the test substance were applied to the maximum area possible on the dorsal skin. Doses covered at least 10 % of the total body surface. Each dose was applied to the skin and overwrapped with gauze bandages (< 8 ply) secured with non-irritating tape. Twenty-four hours following test substance application, the bandages were removed, and the sites were wiped with disposable paper towels moistened with tepid tap water.

Duration of exposure:

24 hours

Doses:

Single dose

No. of animals per sex per dose:

Five males and five females

Control animals:

no

Details on study design:

MORTALITY
- The rats were observed at approximately 1, 2, and 4 hours post-application on study day 0 and twice daily, once in the morning and once in the afternoon, thereafter for 14 days.

CLINICAL OBSERVATIONS
- The rats were observed at approximately 1, 2, and 4 hours post-application on study day 0 and once daily thereafter for 14 days.
- Observations included, but were not limited to, evaluation for changes in appearance of skin and fur, eyes, mucous membranes, respiratory and circulatory systems, autonomic effects, and central nervous system effects.

DERMAL OBSERVATIONS
- The application sites were examined for erythema, edema, and other dermal findings (see Appendix C, attached) beginning 30–60 minutes after bandage removal and daily thereafter through Study Day 14.
- The areas of application were clipped free of hair on the day prior to dosing and as needed to facilitate accurate dermal observations.

BODY WEIGHTS
- Body weights were obtained and recorded on Study Days 0 (initiation), 7, and 14 (termination).

NECROPSY
- Upon termination, all rats were euthanized by carbon dioxide inhalation.
- The major organ systems of the cranial, thoracic, and abdominal cavities were examined for all animals.
- Tissues were not collected.

DATA ACQUISITION AND ANALYSIS
- The major computer systems used on this study include, but are not limited to, those listed in the attached table.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- There were no deaths during the study.

Clinical signs:

- Summary data are shown in Table 1 (attached) and individual data are given in Table 5 (attached).
- There were no clinical observations noted during the study.

Body weight:

- Summary data are shown in Tables 2 and 3 (attached) and individual data are given in Tables 7 and 8 (attached).
- There were no remarkable body weight changes noted during the study.

Gross pathology:

- Summary data are shown in Table 4 (attached) and individual data are given in Table 9 (attached).
- There were no macroscopic findings at the scheduled necropsy.

Other findings:

DERMAL OBSERVATIONS
- Summary data are shown in Table 1 (attached) and individual data are given in Table 6 (attached).
- Dermal findings noted during the study consisted of very slight (grade 1) to slight (grade 2) erythema and desquamation for all 5 males and 5 females.
- The erythema subsided by study day 6, and desquamation subsided by study day 11. In addition, female numbers 5126 and 5129 had scabbing within the dose site on study day 2 and 3, respectively.
- There was no oedema observed at any dose site.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item was greater than 2000 mg/kg when administered once for 24 hours to the clipped, unabraded skin of male and female albino rats.

Executive summary:

GUIDELINE

The study was designed to be in general compliance with the EPA OPPTS Guideline 870.1200 (1996):“Acute Dermal Toxicity”and the OECD Guidelines for Testing of Chemicals, Section 402 (1987):“Acute Dermal Toxicity”. The objective was to determine the acute dermal median lethal dose (LD50), evaluate potential systemic toxicity, and evaluate the local irritative effects of the test substance when applied once to the skin of albino rats.

 

METHODS

The test substance was administered once dermally for a 24-hour period under semi-occlusive dressing to Crl:CD(SD) albino rats to perform the limit test. The test substance was administered to one group of 5 male and 5 female rats at a dose level of 2000 mg/kg. Mortality, clinical observations, dermal findings and body weight changes were evaluated over a 14-day observation period. All animals were subjected to a gross necropsy.

 

There were no deaths, clinical observations, remarkable body weight changes, or test substance-related gross necropsy findings. Dermal findings noted during the study consisted of very slight (grade 1) to slight (grade 2) erythema and desquamation for all 5 males and 5 females and scabbing within the dose site for 2 females.

 

CONCLUSION

The LD50 of the test item was greater than 2000 mg/kg when administered once for 24 hours to the clipped, unabraded skin of male and female albino rats.