Cholesterol

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb-May 2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was not performed according to GLP guideline but similar to OECD or EC guideline. No information on the purity is provided. However, the results are considered reliable for this endpoint.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

purity not stated; no details on dosing

Principles of method if other than guideline:

Study performed according to the method described by Hagan, EC (Acute Toxicity, Appraisal of the safety of chemicals in food, drugs and cosmetics; The Association of Food and Drug Officials of the United States, 1959, pp 17-25).

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: suitable licensed dealer, not specified
- Age at study initiation: 7 to 10 weeks
- Weight at study initiation: 202 to 240 grams
- Fasting period before study: 18 hours
- Housing: stainless steel cages with indirect bedding
- Diet: ad libitum, Lab Diet Certified Rodent Diet #5002
- Water: ad libitum
- Acclimation period: at least 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): monitored, not specified
- Air changes (per hr): no information
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28 Feb 2008 (males) or 3 May 2008 (females) To: 14 March 2008 (males) or 17 May 2008 (females)

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing, mortality and clinical signs at 1, 3, 6 and 24 hours after dosing, and at least once daily therafter for a total of 14 days; initial and terminal body weights were recorded.
- Necropsy of survivors performed: yes

Statistics:

not performed, not required.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: No significant clinical signs were observed (mucoid diarrhea in 4 males at 3 hours after administration only).

Gross pathology:

no gross changes were observed

Other findings:

none

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Exposure to 2000 mg/kg bw cholesterol of male and female rats did not result in mortality.

Executive summary:

Sprague Dawley rats (5/sex) were given 2000 mg/kg bw cholesterol by oral gavage. Animals were observed for 14 days for mortality, clinical signs, and body weights were recorded at the start and at the end of the study. All animals survived the 14 day observation period. All animals gained weight, and no clinical signs or gross changes were observed. Based on the absence of mortality at the tested dose of 2000 mg/kg bw, cholesterol does not have to be classified and has no obligatory labelling requirement for acute oral 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 clasification , labelling and packaging of substances and mixtures.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

One reliable study available.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

One reliable study available.

Additional information

oral:

Sprague Dawley rats (5/sex) were given 2000 mg/kg bw cholesterol by oral gavage. Animals were observed for 14 days for mortality, clinical signs, and body weights were recorded at the start and at the end of the study. All animals survived the 14 day observation period. All animals gained weight, and no clinical signs or gross changes were observed.

dermal:

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.

Justification for selection of acute toxicity – oral endpoint
Reliable study for acute oral toxicity.

Justification for selection of acute toxicity – inhalation endpoint
According to REACH

Justification for selection of acute toxicity – dermal endpoint
The study is reliable and was performed according to OECD and US EPA guidelines and according to GLP principles.

Justification for classification or non-classification

Based on the absence of mortality at the tested dose of 2000 mg/kg bw, cholesterol does not have to be classified and has no obligatory labelling requirement for acute oral toxicity and 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 clasification , labelling and packaging of substances and mixtures.