4-Decenal, 9-hydroxy-5,9-dimethyl-

Endpoint summary

Description of key information

Oral

Oral LD50 > 2000 mg/kg bw (OECD 420, K, Rel.1, Fixed dose Method adopted in December 2001)

Inhalation

No data

Dermal

Dermal LD50 > 2000 mg/kg bw (OECD 402, K, Rel.1, Acute Dermal Toxicity adopted in February 1987)

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:

Between 25 June 2013 and 23 July 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study performed according to OECD test guideline No. 420 and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

No. 440/2008

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: 10 July 2012/Signed on 30/11/12

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS (RccHanTM:WIST)
- Source: Harlan Laboratories UK Ltd, Oxon UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 152-179 g
- Fasting period before study: overnight. Food will be returned approximately 3 to 4 hours after dosing.
- Housing: grouped in group of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Rodent 2014C Teklad Global Rodent Diet ad libitum. Not contaminated.
- Water (e.g. ad libitum): Tap water ad libitum. Not contaminated.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30-70 %
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): the test item was formulated within two hours of being applied in the test system. It is assumed that the formulation was stable for this duration.

Doses:

Sighting test: 300 mg/kg bw and 2000 mg/kg bw
Main test: 2000 mg/kg bw

No. of animals per sex per dose:

Sighting test: 1 female/dose
Main test: 4 additional females

Control animals:

no

Details on study design:

SIGHTING TEST
A single animal was treated as the dose level of 300 mg/kg bw. In the absence of toxicity at 300 mg/kg bw, an additional animal was treated at the dose level of 2000 mg/kg bw.

MAIN TEST
In the absence of toxicity at 2000 mg/kg bw, an additional group of four animals was treated at the dose level of 2000 mg/kg bw.

- Duration of observation period following administration: 14 days
- Frequency of mortality / morbidity inspection: twice daily, early and late, during normal working dates, once daily at weekends and public holidays.
- Frequency of clinical observations: 30 min, 1, 2 and 4 hours after dosing, then at least once daily.
- Weighing: recorded on Day 0 (prior to dosing), Day 7 and 14, or at death.
- Necropsy of survivors performed: yes, gross necropsy on all animals (external examination and opening of the abdominal and thoracic cavities.

Statistics:

None

Preliminary study:

In the absence of mortality at a dose level of 300 and 2000 mg/kg bw, an additional group of animals (4 rats) was treated at the high dose level.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Oral LD50 Females > 2000 mg kg bw.

Executive summary:

In an acute oral toxicity study performed according to the OECD test guideline No. 420 and in compliance with GLP, groups of fasted, eight to twelve weeks of age Wistar (RccHan^TM:WIST) female rats were given a single oral dose of the test item as a solution in Arachis oil BP. Following a sighting test using two animals at the dose level of 300 and 2000 mg/kg bw, an additional four fasted female animals were given a single oral dose of test item, at 2000 mg/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

 

There were no deaths during the study and no abnormalities noted at necropsy. No signs of systemic toxicity were noted during the observation period and all animals showed expected gains in bodyweight.

 

Oral LD₅₀ Females > 2000 mg/kg bw

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Under the test conditions, the test item is not classified as toxic if swallowed and did not meet the criteria for classification according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS. This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP compliant and of high quality (Klimisch score = 1)

Acute toxicity: via inhalation route

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:

From 26 June to 17 july 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 402 without any deviation.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

No. 440/2008

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on July 10, 2012/ signed on November 30, 2012)

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: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 225-248 g (males); 200-220 g (females)
- Housing: Animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. Animals were housed individually during the 24 hour exposure period and in groups of five by sex for the remainder of the study.
- Diet: Food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 15 changes/h
- Photoperiod: 12 h dark / 12 h light

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Pretreatment: On the day before treatment the back and flanks of each animal were clipped free of hair.
- Area of exposure: Back and flank area
- % coverage: Approximately 10 % of the total body surface area.
- Application of test item: Test item was used as supplied. The test item was applied as evenly as possible to an area of shorn skin using a graduated syringe.
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually for the 24 hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item. The animals were returned to group housing for the remainder of the study period.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Specific gravity of test item: 0.932
- Constant volume or concentration used: Yes; 2.15 mL/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

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: Animals were observed for mortality or clinical signs of toxicity at 0.5, 1, 2 and 4 h after dosing and subsequently once daily for 14 days. After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored according to Draize scale.
- Frequency of weighing: Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes; at the end of the study animals were killed by cervical dislocation and subjected to gross necropsy.

Statistics:

None

Preliminary study:

No mortality was noted.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed

Mortality:

No mortality was observed.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Very slight erythema was noted at the test sites of four females up to six days after treatment. There were no signs of dermal irritation noted at the test sites of the remaining animals.

None

Interpretation of results:

GHS criteria not met

Conclusions:

Dermal LD50 Combined > 2000 mg/kg bw. Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

Executive summary:

In an acute dermal toxicity study (limit test) performed according to OECD Guideline No. 402 and in compliance with GLP, a single dermal application of the undiluted test item at 2000 mg/kg bw was administered to the intact skin of the back and flank area of a group of Wistar (RccHan™:WIST) rats (5/sex) at the dose volume of 2.15 mL/kg bw. Test sites were covered with a semi-occlusive dressing for 24 h.

Animals were observed for mortality, clinical signs and body weights for 14 days. At the end of the study, the surviving animals were sacrificed for macroscopic examination. Skin irritation was assessed and scored according to the Draize scale at 24 h after removal of the dressings and then daily for 14 days.

 

No mortality or systemic toxicity was observed. Very slight erythema was noted at the test sites of four females up to six days after treatment. There were no signs of dermal irritation noted at the test sites of the remaining animals. All animals showed expected gains in body weight over the study period. No abnormalities were noted at necropsy.

 

Dermal LD50 Combined > 2000 mg/kg bw

 

The acute dermal median lethal dose (LD50) of the test item in Wistar rats was found to be greater than 2000 mg/kg body weight.

Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No.1272/2008 (CLP) and to GHS. This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The key study is GLP compliant and of high quality (Klimisch score = 1)

Additional information

ORAL

A key study was identified (Harlan, 2013, rel. 1).

In an acute oral toxicity study performed according to the OECD test guideline No. 420 and in compliance with GLP, groups of fasted, eight to twelve weeks of age Wistar (RccHanTM:WIST) female rats were given a single oral dose of the test item as a solution in Arachis oil BP. Following a sighting test at 300 and 2000 mg/kg bw (one animal/dose), an additional four fasted female animals were given a single oral dose of test item at 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

 

There were no deaths during the study and no abnormalities noted at necropsy. No signs of systemic toxicity were noted during the observation period and all animals showed expected gains in body weight.

Oral LD50 Females > 2000 mg/kg bw

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Under the test conditions, the test item is not classified as toxic if swallowed and did not meet the criteria for classification according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS. This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

 

DERMAL

A key study was identified (Harlan, 2013, rel. 1).

In an acute dermal toxicity study (limit test) performed according to OECD Guideline No. 402 and in compliance with GLP, a single dermal application of the undiluted test item at 2000 mg/kg bw was administered to the intact skin of the back and flank area of a group of Wistar (RccHan™:WIST) rats (5/sex) at the dose volume of 2.15 mL/kg bw. Test sites were covered with a semi-occlusive dressing for 24 h. Animals were observed for mortality, clinical signs and bodyweights for 14 days. At the end of the study, the surviving animals were sacrificed for macroscopic examination. Skin irritation was assessed and scored according to the Draize scale at 24 h after removal of the dressings and then daily for 14 days.

 

No mortality or systemic toxicity were observed. Very slight erythema was noted at the test sites of four females up to six days after treatment. There were no signs of dermal irritation noted at the test sites of the remaining animals. All animals showed expected gains in body weight over the study period. No abnormalities were noted at necropsy.

 

Dermal LD50 Combined > 2000 mg/kg bw

The acute dermal median lethal dose (LD50) of the test item in Wistar rats was found to be greater than 2000 mg/kg body weight.

Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No.1272/2008 (CLP) and to GHS. This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity (Oral)

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Under the test conditions, the test item is not classified as toxic if swallowed and did not meet the criteria for classification according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS. No signal word or hazard statement is required. 

Acute toxicity (Dermal)

The acute dermal median lethal dose (LD50) of the test item in Wistar rats was found to be greater than 2000 mg/kg body weight.

Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No.1272/2008 (CLP) and to GHS. No signal word or hazard statement is required.

Acute toxicity (Inhalation)

Not required for substances at the REACH Annex VII tonnage level.

Specific target organ toxicity: single exposure (Oral)

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal)

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw≥C > 1000 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute dermal toxicity study.

Specific target organ toxicity: single exposure (Inhalation)

No information was available. Not required for substances at the REACH Annex VII tonnage level.

Aspiration hazard

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.