6-cyclopentylidenehexanal

Endpoint summary

Description of key information

Oral LD50 > 300 mg/kg bw - < 2000 mg/kg bw. The LD50 cut-off: 1000 mg/kg bw (OECD 423, K, Rel.1)

Dermal LD50 > 2000 mg/kg bw (OECD 402, K, Rel.1)

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 05 to 26 February 2013.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 423 without any deviation.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

17 December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2012-04-23&24 / Signed on 2012-07-18.

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Date received: 23 January 2013
- Storage condition of test material: 6°C±3°C

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle, France)
- Age at study initiation: 8 or 9 weeks
- Weight at study initiation: 185 - 219 g
- Housing: housed by group of three in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff (SAFE, A04), ad libitum.
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70%
- Air changes: between ten and fifteen changes per hour.
- Photoperiod: 12 h light/12 h darkness.

IN-LIFE DATES: From 05 to 26 February 2013.

Route of administration:

oral: gavage

Vehicle:

other: at 2000 mg/kg bw: none. At 300 mg/kg bw: water.

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.15 mL/kg bw

ADMINISTRATION OF TEST ITEM:
* In the first step: animals received an effective dose of 2000 mg/kg bw of the test item, administered by force-feeding under a volume of 2.15 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.
* In the second step: animals received an effective dose of 300 mg/kg bw of the test item (0.32 mL of the test item was added to 1.83 mL of distilled water), administered by force-feeding under a volume of 2.15 mL/kg bw using a suitable syringe graduated fitted with an oesophageal metal canula.

VEHICLE
- Amount of vehicle (if gavage): 1.83 mL (second step, at 300 mg/kg bw)
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 (2000 mg/kg bw) and 6 (300 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min, 1, 3 and 4 hours after test item administration and thereafter once daily for 14 days. Animals were weighed pretest (Day 0) and on Day 2, 7 and 14.
- Necropsy of survivors performed: Yes; Animals were killed on Day 14 and subjected to macroscopic examination.

Statistics:

None

Preliminary study:

Not applicable

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

ca. 1 000 mg/kg bw

Based on:

test mat.

Mortality:

- At 2000 mg/kg b.w: it was noted the death of two rats (2/3), at 22 hours and 50 minutes post-dose.
- At 300 mg/kg b.w: no mortality occurred.

Clinical signs:

other: - At 2000 mg/kg b.w: the mortalities were preceded by decrease in spontaneous activity (2/2) and piloerection (1/2). Rigor mortis was noted before the necropsy (2/2). In the surviving animal treated at 2000 mg/kg b.w. (1/3), a decrease in spontaneous act

Gross pathology:

- At 2000 mg/kg b.w: the macroscopic examination revealed a thinning of the forestomach and of the corpus (2/2) associated with black and red spots on the forestomach and on the corpus (2/2).
- At 300 mg/kg b.w: the macroscopical examination of the animals at the end of the study did not reveal treatment-related changes.

Other findings:

None

None

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the test conditions, the oral LD50 for test item is higher than 300 mg/kg and lower than 2000 mg/kg bw and the LD50 cut-off may be considered as 1000 mg/kg bw in female rats. Therefore, it must be classified in Category 4 according to the CLP Regulation (EC) No. 1272/2008 and Globally Harmonized System (GHS).

Executive summary:

In an acute oral toxicity study (limit test) performed according to OECD Guideline 423 and in compliance with GLP, 3 female Sprague Dawley rats were given a single oral (gavage) dose of test item at 2000 mg/kg bw and then 6 female Sprague Dawley rats were given a single oral (gavage) dose of test item at 300 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

It was noted the death of two rats treated at 2000 mg/kg b.w. (2/3). The mortalities were preceded by decrease in spontaneous activity (2/2) and piloerection (1/2). Rigor mortis was noted before the necropsy (2/2). Decrease in body weight was noted in the two animals on the day of the death compared to day 0 (between -11% and -15%) The macroscopic examination revealed a thinning of the forestomach and of the corpus (2/2) associated with black and red spots on the forestomach and on the corpus (2/2). In the surviving animal treated at 2000 mg/kg b.w. (1/3), a decrease in spontaneous activity, bradypnea, total ptosis, and piloerection were noted during the first days of the test. The animal recovered a normal behaviour at 48 hours post-dose. An absence in body weight gain was noted on day 2 compared to day 0. Then, the body weight evolution remained normal. The macroscopic examination of this animal at the end of the study did not reveal treatment related changes.

No mortality occurred in animals treated at 300 mg/kg. A decrease in spontaneous activity (3/6), and piloerection (2/6) were noted during the first hours of the test. The animals recovered a normal behaviour at 4 hours post-dose. The body weight evolution remained normal during the study.The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

Under the test conditions, the oral LD50 for test item is higher than 300 mg/kg and lower than 2000 mg/kg bw and the LD50 cut-off may be considered as 1000 mg/kg bw in female rats. Therefore, it must be classified in Category 4 (H302: Harmful if swallowed) according to the CLP Regulation (EC) No. 1272/2008 and Globally Harmonized System (GHS).

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 000 mg/kg bw

Quality of whole database:

The key study is GLP compliant and of high quality.

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 5 to 19 February 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:

24 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2012-04-23&24 / Signed on 2012-07-18

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Date received: 23 January 2013
- Storage condition of test material: 6°C±3°C

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (539040 Le Genest St Isle-France)
- Age at study initiation: 7 weeks (males ) and 8 weeks (females)
- Weight at study initiation: 245 - 266 g (males) and 212 - 228 g (females).
- Housing: Animals were housed individually during the 24 h exposure period and in groups of five by sex for the remainder of the study in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff (SAFE - A04), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 °C
- Humidity: 30-70 %
- Air changes: 10-15 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From 5 to 19 February, 2013

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST ITEM FORMULATION AND EXPERIMENTAL PREPARATION
- An effective dose of 2000 mg/kg body weight administered under a volume of 2.15 mL/kg body weight (corresponding to 2g/kg, according to the calculated density), during 24 hours.

TEST SITE
- Area of exposure: Back and flank area
- % coverage: The appropriate amount of test item, moistened with liquid paraffin, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area).
- 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.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: Yes

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 and weighing: 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. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 2, 7 and 14.
- After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the Draize scale.
- Necropsy of survivors performed: Yes; at the end of the study animals were anaesthetised with sodium pentobarbital and administration continued to fatal levels.

Statistics:

None

Preliminary study:

Not applicable

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. - Dermal reactions: cutaneous reactions (erythema) were noted from 24 hours post-dose in all animals and were totally reversible on day 2 in males and on day 8 in females. Dryness w

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the dermal LD50 Combined for test substance is higher than 2000 mg/kg bw in rats. Therefore, the substance is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute dermal toxicity study (limit test) performed according to OECD Guideline No. 402 and in compliance with GLP, a group of Sprague Dawley rats (5/sex) was given a single dermal application of the test material to intact skin of the back and flank area at a dose level of 2000 mg/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 and 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. Cutaneous reactions (erythema) were noted from 24 hours post-dose in all animals and were totally reversible on day 2 in males and on day 8 in females. Dryness was noted on day 3 in all females and was totally reversible between days 5 and 8. All animals showed gains in body weight over the observation period. No abnormalities were noted at necropsy.

 

Dermal LD50 Combined > 2000 mg/kg bw

 

Under the test conditions, the test material is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the 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.

Additional information

 

Acute toxicity: oral

A key study was identified (Phycher, 2013, rel. 1). In this acute oral toxic class method study performed according to the OECD guideline No. 423 and in compliance with GLP, three female Sprague Dawley rats received a single oral (gavage) dose of the test substance at a dose level of 2000 mg/kg bw and then 6 female Sprague Dawley rats were given a single oral (gavage) dose of test item at 300 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

It was noted the death of two rats treated at 2000 mg/kg b.w. (2/3). The mortalities were preceded by decrease in spontaneous activity (2/2) and piloerection (1/2). Rigor mortis was noted before the necropsy (2/2). Decrease in body weight was noted in the two animals on the day of the death compared to day 0 (between -11% and -15%) The macroscopic examination revealed a thinning of the forestomach and of the corpus (2/2) associated with black and red spots on the forestomach and on the corpus (2/2). In the surviving animal treated at 2000 mg/kg b.w. (1/3), a decrease in spontaneous activity, bradypnea, total ptosis, and piloerection were noted during the first days of the test. The animal recovered a normal behaviour at 48 hours post-dose. An absence in body weight gain was noted on day 2 compared to day 0. Then, the body weight evolution remained normal. The macroscopic examination of this animal at the end of the study did not reveal treatment related changes.

 

No mortality occurred in animals treated at 300 mg/kg. A decrease in spontaneous activity (3/6), and piloerection (2/6) were noted during the first hours of the test. The animals recovered a normal behaviour at 4 hours post-dose. The body weight evolution remained normal during the study.The macroscopic examination of the animals at the end of the study did not reveal treatment related changes.

 

Oral LD50 > 300 mg/kg bw - < 2000 mg/kg bw and the LD50 cut-off may be considered as 1000 mg/kg bw.

 

Acute toxicity: dermal

A key study was identified (Phycher, 2013, rel.1). In this acute dermal toxicity study (limit test) performed according to OECD Guideline No. 402 and in compliance with GLP, a group of SD rats (5/sex) was given a single dermal application of the undiluted test material to intact skin of the back and flank area at a dose level of 2000 mg/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 and 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. Cutaneous reactions (erythema) were noted from 24 hours post-dose in all animals and were totally reversible on day 2 in males and on day 8 in females. Dryness was noted on day 3 in all females and was totally reversible between days 5 and 8. All animals showed gains in body weight over the observation period. No abnormalities were noted at necropsy.

 

Dermal LD50 Combined > 2000 mg/kg bw

 

Justification for classification or non-classification

 

Harmonized classification:

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

 

Self classification:

Acute toxicity (Oral):

Based on the available information, the substance is classified in Category 4 (H302: Harmful if swallowed) according to the CLP and to the GHS.

 

Acute toxicity (Dermal):

Based on the available information, the substance is:

- not classified according to the CLP as the dermal LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

 

Acute toxicity (Inhalation):

No information was available. 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.