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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EPA OPPTS 870.1200
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MAFF Japan Test Guidelines for Agricultural Chemicals 12-Nousan-8147 (2000)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
D-mannose
EC Number:
222-392-4
EC Name:
D-mannose
Cas Number:
3458-28-4
Molecular formula:
C6H12O6
IUPAC Name:
D-mannose
Test material form:
solid: particulate/powder
Details on test material:
Purity: >99%

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: Mean rat weight: Male - 296.1 g; Female - 219.1 g
- Fasting period before study: not reported
- Housing: housed individually in solid-bottom caging with bedding and appropriate species-specific enrichment
- Diet: PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6-day quarantine period


ENVIRONMENTAL CONDITIONS
- Temperature: 20-26ºC
- Humidity: 30-70%
- Photoperiod: approximate 12-hour light/dark cycle

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
5000 mg/kg body weight
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
5
Details on study design:
TEST SITE
- Area of exposure: The paste was spread evenly, directly on the skin, covering an area of approximately 37 square centimetres.
- % coverage: Thirty-seven square centimeters is equal to approximately 10 percent of the total body surface area of rats in the 200 - 300 g body weight range.
- Type of wrap if used: The test substance was covered with a 2-ply gauze patch. The rats were then wrapped with stretch gauze bandage and self-adhesive bandage.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: Approximately 24 hours after treatment,
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test substance was measured for each animal on the day of treatment at a dose of 5000 mg/kg of body weight. The amount of test substance designated for each animal was calculated based on body weights collected prior to treatment.
- For solids, paste formed: yes
VEHICLE
- Amount(s) applied (volume or weight with unit): The aliquot of test substance designated for an animal was moistened with approximately 1 mL of deionized water to form a thick paste.

- Duration of observation period following administration: 15 days
- Frequency of observations: Daily animal health observations were conducted throughout the study for mortality and signs of illness, injury, and abnormal behaviour. The rats were weighed on test days 1, 8, and 15, and were observed daily for clinical signs of toxicity and dermal irritation (weekends and holidays excluded for dermal irritation)
- Other examinations performed: All rats were euthanized at the end of the 15-day test period and examined to detect grossly observable evidence of organ or tissue damage.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
other: all animals
Time point:
other: 24-hours to 14 days
Score:
1
Reversibility:
fully reversible within: 2 days
Remarks on result:
other:
Remarks:
On test day 1 and 2, erythema was observed in 3/5 male animals, with a score of 1. All erythema was resolved by test day 3.
Irritation parameter:
edema score
Basis:
other: all animals
Time point:
other: 24 hours to 14 days
Remarks on result:
other: no oedema observed
Irritant / corrosive response data:
At the beginning of the observation period (approximately 24 hours after exposure), on test day 2, erythema was observed in 3/5 male animals, with a score of 1. All erythema was resolved by test day 3. There were no instances of edema observed.
Other effects:
Refer to acute dermal toxicity study DI.K1.Derm.R.D-21373-673.KD in IULICD section 7.2.3 (Acute toxicity: dermal) for additonal information.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
At the beginning of the observation period (approximately 24 hours after exposure), on test day 2, erythema was observed in 3/5 male animals, with a score of 1. All erythema was resolved by test day 3. There were no instances of edema observed. These findings do not meet the criteria for classifying for skin irritation.
Executive summary:

A single dose of the test item was applied to the shaved, intact skin of 5 male and 5 female rats at a dose level of 5000 mg/kg of body weight. The application site was covered with a semi-occlusive dressing for 24 hours, after which the test substance was removed. The rats were observed for 14 days following application. The rats were necropsied to detect grossly observable evidence of organ or tissue damage at the end of the 15-day test period.

 

There were no incidents of mortality and no overall body weight losses. One male exhibited scabbing on the right shoulder, between test days 12-15. No other clinical abnormalities were observed. At the beginning of the observation period (approximately 24 hours after exposure), on test day 2, erythema was observed in 3/5 male animals, with a score of 1. All erythema was resolved by test day 3. There were no instances of edema observed. No gross lesions were present in the rats at necropsy.

 

Under the conditions of this study, the dermal LD50 for the test item was greater than 5000 mg/kg of body weight when applied to the skin of male and female rats for 24 hours.

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