Cholesterol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to EU/OECD and US EPA guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revision

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cholesterol

EC Number:

200-353-2

EC Name:

Cholesterol

Cas Number:

57-88-5

Molecular formula:

C27H46O

IUPAC Name:

cholest-5-en-3-ol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Cholesterol
- Substance type: powder
- Physical state: white powder
- Storage condition of test material: at room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 12 weeks old
- Weight at study initiation: males: 268 - 299 grams; females: 189 - 207 grams
- Fasting period before study: no
- Housing: individually housed in Makrolon cages (MIII type) with sterilized sawdust as bedding material and paper as cage-enrichment
- Diet: free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: free access to tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 05 June 2012 To: 19 June 2012

Administration / exposure

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: 25 cm2 for males anad 18 cm2 for females
- % coverage: approx. 10
- Type of wrap if used: surgical gauze patch (Surgy 1D) covered with aluminium foil and Coban elastic bandage. In females additionally Micropore tape was used for fixation.

REMOVAL OF TEST SUBSTANCE
- Washing: with tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied (volume or weight with unit): 10 mL/kg bw
- Concentration (if solution): 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: no

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw/day

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality: twice daily; body weights: days 1, 8 and 15; clinical signs: at periodic intervals on Day 1, once daily thereafter
- Necropsy of survivors performed: yes, animals were sacrificed by oxygen/carbon dioxide and subjected to necropsy. All internal macroscopic abnormalities were recorded.

Statistics:

Not performed; not required.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: Day 1: chromodacryorrhoea was shown by most animals; two animals showed ptosis and/or hunched posture. Days 7 and 15: four animals showed scales and/or scabs on the treated skin-area.

Gross pathology:

Three females showed reddish discolouration of the thymus.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 value of Cholesterol in Wistar rats was established to exceed 2000 mg/kg bw/day.

Executive summary:

In an acute dermal toxicity study in Wistar rats performed according to OECD guideline 402, cholesterol was administered to 5 rats of each sex by a single dermal application at 2000 mg/kg bw for 24 hours. No mortality occurred. On Day 1 most animals showed chromodacryorrhoea, and two animals showed ptosis and/or hunched posture. Between Days 7 and 15 scales and/or scabs were seen on the treated skin-area of four animals. Macroscopic examination showed reddish discolouration of the thymus in three females.

Based on the absence of mortality, the LD50 value of Cholesterol in Wistar rats was established to exceed 2000 mg/kg bw. Based on these results, Cholesterol does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the:

-Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),

-Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.