Reaction mass of undec-8-enal and undec-9-enal and undec-10-enal

Endpoint summary

Description of key information

Acute oral toxicity: > 5000 mg/kg bw (read-across from Undec-10-enal tested in OECD TG 401)

Acute dermal toxicity: > 5000 mg/kg bw (read-across from Undec-10-enal tested in OECD TG 402)

Acute inhalation toxicity using route to route extrapolation from the oral route: > 13000 mg/m3

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The result derived from read across is sufficiently reliable because all Annex XI criteria are met.

Justification for type of information:

The read across justification is presented in the Endpoint summary and the accompanying files are also attached there.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

other: Not acute toxic

Remarks:

according to EU CLP criteria (1272/2008/EC and its updates)

Conclusions:

Based on the results of the study for read-across substance Undec-10-enal, an acute oral LD50 of >5000 mg/kg bw was determined for Intreleven aldehyde.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

non-GLP, pre-OECD

Justification for type of information:

The information is used for read across to Intreleven aldehyde.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Remarks:

pre-GLP

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
- Weight at study initiation: 150-300 grams
- Fasting period before study: yes, overnight
- Housing: Individually
- Diet (e.g. ad libitum): commercial diet
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% (v/v)
- Justification for choice of vehicle: not specified

Doses:

5 g/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: after one and four hours, and thereafter daily.
- Necropsy of survivors performed: yes.
- Other examinations performed: toxic signs and mortality were recorded.

Statistics:

The LD50 was calculated according to Horn's method (Horn, H.J., Biometrics, 12, 311-322, 1956).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

Toxic signs found were diarrhea, depression and salivation.

Body weight:

No information.

Gross pathology:

Abnormalities were noted.

Other findings:

None.

Interpretation of results:

other: Not acute toxic

Remarks:

according to EU CLP criteria (1272/2008/EC and its updates)

Conclusions:

Under the conditions of this test, an acute oral LD50 of >5000 mg/kg bw was determined for Undec-10-enal.

Executive summary:

An acute oral toxicity study was performed according to a method similar to OECD TG 401, as the study was performed non-GLP and pre-OECD (it was rated Klimisch 2). In this study, 10 rats were orally administered Undec-10-enal at a dose level of 5000 mg/kg bw. The mortality rate of the rats was 0/10. Clinical signs observed were diarrhea, depression and salivation. Gross necropsy was performed at end of term, but no abnormalities were found. Under the conditions of this test, an acute oral LD50 of >5000 mg/kg bw was determined for Undec-10-enal.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Comparable to guideline study with acceptable restrictions

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The result derived from read across is sufficiently reliable because all Annex XI criteria are met.

Justification for type of information:

The read across justification is presented in the Endpoint summary and the accompanying files are also attached there.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

other: Not acute toxic

Remarks:

according to EU CLP criteria (1272/2008/EC and its updates)

Conclusions:

Based on the results of the study for read-across substance Undec-10-enal, an acute dermal LD50 of >5000 mg/kg bw was determined for Intreleven aldehyde.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

non-GLP, pre-OECD

Justification for type of information:

The information is used for read across to Intreleven aldehyde.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5-3 kg
- Housing: Individually
- Diet (e.g. ad libitum): commercial diet
- Water (e.g. ad libitum): ad libitum

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 240 cm2
- % coverage: 10% of body surface
- clipped (in half of the animals the skin was lightly abraded)
- Type of wrap: the liquid test material was delivered under a rubber sleeve by using a hypodermic syringe, then the sleeve was covered with Webril padding. The rabbit was fitted with a collar to prevent the removal of the wrapping.

Duration of exposure:

24 hours

Doses:

5 ml/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: toxic signs, (local) dermal effects and mortality.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal died during the study, no postmortem abnormalities were found.

Clinical signs:

Edema was found in 3/6 animals, Erythema in 5/6. Other dermal reaction occured, such as discoloration (3/6), scaling (3/6), necrosis (1/6) and eschar formation (3/6).

Body weight:

No information.

Gross pathology:

No abnormalities were found.

Other findings:

None.

Interpretation of results:

other: Not acute toxic

Remarks:

according to EU CLP criteria (1272/2008/EC and its updates)

Conclusions:

Under the conditions of this test, an acute dermal LD50 of >5000 mg/kg bw was determined for Undec-10-enal.

Executive summary:

An acute dermal toxicity study was performed according to a method similar to OECD TG 402, as the study was performed non-GLP and pre-OECD (it was rated Klimisch 2). In this study, 6 healthy albino rabbits were dosed dermally with Undec-10-enal at 5000 mg/kg bw. In half of the animals the skin was lightly abraded. The test article was kept in contact with the skin for 24 hours. One rabbits died and five rabbits survived the 5000 mg/kg bw dermal dose. Gross necropsy did not reveal any abnormalities. Clinical signs found were: edema (in 3/6 animals), erythema (in 5/6) and other dermal reactions occurred, such as discoloration (3/6), scaling (3/6), necrosis (1/6) and eschar formation (3/6). Under the conditions of this test, an acute dermal LD50 of >5000 mg/kg bw was determined for Undec-10-enal.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Comparable to guideline study with acceptable restrictions

Additional information

The acute oral and dermal toxicity of Intreleven aldehyde was assessed by using read across from Undec-10-enal. First the experimental acute toxicity information of Undec-10-enal will be summarised. Thereafter the read across justification is presented, the accompanying files are attached in the present endpoint summary.

The OECD 401 acute oral toxicity study with Undec-10 -enal used for read across to Intreleven aldehyde:

An acute oral toxicity study was performed according to a method similar to OECD TG 401, as the study was performed non-GLP and pre-OECD (it was rated Klimisch 2). In this study, 10 rats were orally administered Undec-10-enal at a dose level of 5000 mg/kg bw. The mortality rate of the rats was 0/10. Clinical signs observed were diarrhea, depression and salivation. Gross necropsy was performed at end of term, but no abnormalities were found. Under the conditions of this test, an acute oral LD50 of >5000 mg/kg bw was determined for Undec-10-enal.

The OECD 402 acute dermal toxicity study with Undec-10 -enal used for read across to Intreleven aldehyde:

An acute dermal toxicity study was performed according to a method similar to OECD TG 402, as the study was performed non-GLP and pre-OECD (it was rated Klimisch 2). In this study, 6 healthy albino rabbits were dosed dermally with Undec-10-enal at 5000 mg/kg bw. In half of the animals the skin was lightly abraded. The test article was kept in contact with the skin for 24 hours. One rabbits died and five rabbits survived the 5000 mg/kg bw dermal dose. Gross necropsy did not reveal any abnormalities. Clinical signs found were: edema (in 3/6 animals), erythema (in 5/6) and other dermal reactions occurred, such as discoloration (3/6), scaling (3/6), necrosis (1/6) and eschar formation (3/6). Under the conditions of this test, an acute dermal LD50 of >5000 mg/kg bw was determined for Undec-10-enal.

Acute inhalation toxicity

The acute inhalation toxicity of Intreleven aldehyde is predicted based on the acute oral toxicity in accordance with the ECHA CLP guidance document (2015, 3.1.3.3.4: 1 mg/kg bw = 0.0052 mg/l (5.2 mg/m3). 5000 mg/kg bw * 0.0052 mg/l = 26 mg/L = 26000 mg/m3. The acute inhalation for Undec-10-enal is therefore predicted to be > 13000 mg/m3 (using 100% inhalation and 50% oral absorption and an LD50 oral of > 5000 mg/kg bw). No adjustment for the molecular weight from Undec-10-enal to Intreleven Aldehyde is needed as they are the same.

Intreleven Aldehyde: The calculated saturated vapour concentration is 417.9 mg/m3, using the following formula: MW * VP (in Pa) *1000 (g to mg) / [(8.3 (gas constant) * 293 (°K)] = 168.28 * 6.04 * 1000 / (8.3 *293). This means that the acute inhalation concentration cannot be reached and therefore no acute inhalation toxicity is anticipated.

The acute oral and dermal toxicity of Intreleven aldehyde (CAS 58296-81-4; Target) using read across from Undec-10-enal (CAS 112-45-8; Source)

 

Introduction and hypothesis for the analogue approach

Intreleven aldehyde is a multi-constituent which consists of the following main constituents: Undec-10 -enal, (9E) Undec-9 -enal, (9Z) Undec-9 -enal and (8E) Undec-8 -enal. These constituents are aldehydes with a linear carbon backbone and contain one C=C double bond at various positions ranging from C 8 to 10. For this substance no acute oral and dermal toxicity data are available. Therefore additional information is used in accordance with Article 13 of REACH where it is said that lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, SARs, grouping and read-across. For assessing the acute oral and dermal toxicity of Intreleven aldehyde the analogue approach is selected because for one closely related analogue, Undec-10-enal, acute oral and dermal toxicity data are available which can be used for read-across.

Hypothesis: Intreleven aldehyde is expected to have the same acute oral and dermal toxicity as Undec-10-enal.

Available information: For the target substance Intreleven aldehyde no information regarding acute toxicity is available. For the source substance Undec-10-enal, an acute oral and an acute dermal study are available (according to OECD TG 401 and 402, Kl. 2), which indicated an acute oral LD50 of > 5000 mg/kg bw and an acute dermal LD50 of > 5000 mg/kg bw.

Target and Source chemical(s): The chemical structure of the target, Intreleven aldehyde and source, Undec-10-enal, are shown in the data matrix, including the physico-chemical properties and toxicological information.

Purity / Impurities:

The components and impurities of the target chemical do not indicate acute oral and acute dermal toxicity other than indicated by the parent substance. The constituents are known for at least 95% and therefore this substance is well characterized.

Analogue approach justification

According to REACH Annex XI an analogue approach and structural alert information can be used to replace testing when information from different sources provides sufficient evidence to conclude that this substance has or does not have a particular dangerous property. The result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation.

Analogue selection: Undec-10-enal was selected as analogue because it is one of the main constituents of Intreleven aldehyde (11%) and acute oral and dermal toxicity data were available for this substance.

Structural similarities and differences: The target chemical, Intreleven aldehyde and the source chemical, Undec-10-enal have a similar linear carbon backbone with a C=C double bond, the same number of carbons and the same functional aldehyde group. The only structural difference is the position of the double bond in the carbon chain of the substances. Some of the constituents of Intreleven aldehyde have the double bond in the chain, while the source substance has it at the end of its chain.

Toxicokinetics: Oral and dermal absorption: Based on the similarity in chemical structure and physico-chemical properties (MW, appearance, VP, WS and log Kow) as presented in the data matrix, the target and the source chemical are expected to have similar absorption characteristics.

Metabolism: As Undec-10-enal is one of the main constituents of Intreleven aldehyde, similar metabolites will be formed. Auto-oxidation of the aldehyde group is expected. Oxidation to a carboxylic acid would yield unsaturated C11 fatty acids, which can be metabolized via beta-oxidation.

Toxicodynamics: The functional group being the key for toxicity for both the target and the source substance is the same aldehyde group and the acid after oxidation. Based on this, Intreleven and Undec-10-enal will have similar toxicity via the oral and dermal route.

Remaining uncertainties: There are no remaining uncertainties as presented above.

Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented in the data matrix in Table 1.

Conclusions on the acute oral and dermal toxicity per endpoint

For the target substance Intreleven aldehyde, the potential for acute oral and dermal toxicity was derived from Undec-10-enal using read across. The results of this read-across assessment based on OECD TG 401 and 402 indicated no acute oral toxicity (LD50 of >5000 mg/kg bw) and no acute dermal toxicity (LD50 of >5000 mg/kg bw). This information can be used for Intreleven aldehyde based on the similarity in structure, toxicokinetics and toxicodynamics.

Final conclusion on hazard and application in the risk assessment: Intreleven aldehyde has an LD50 >5000 mg/kg bw for acute oral and acute dermal toxicity.

 

Data matrix for the read across from Undec-10-enal to Intreleven aldehyde

CHEMICAL NAME	Intreleven aldehyde (Undec-8-enal)	Undec-10-enal
Molecular structure
CAS	58296-81-4	112-45-8
REACH registration	To be registered (Annex VIII)	Registered (2016)
Einecs	261-202-4	203-973-1
Molecular formula	C11H20O	C11H20O
Molecular weight	168.28	168.28
Physico-chemical properties
Appearance	Liquid	Colorless liquid
Melting point (°C)	<-20 (IFF, 2016)	<-16.6 (ECHA dissemination)
Boiling point (°C)	239.1 (IFF, 2016)	179 (ECHA dissemination)
Vapour pressure (Pa)	6.04 (IFF, 2016)	8.71 (ECHA dissemination)
Water solubility (mg/L)	26.1 (IFF, 2016)	21.52 (ECHA dissemination)
LogKow	4.47 (IFF, 2017)	4.67 (ECHA dissemination)
Human health
Acute oral toxicity	Read across from Undec-10-enal	LD50 > 5000 mg/kg bw (OECD TG 401)
Acute dermal toxicity	Read across from Undec-10-enal	LD50 > 5000 mg/kg bw (OECD TG 402)
Genotoxicity - Ames	Negative (OECD TG471)	Negative (OECD TG471)
Repeated dose toxicity	NOAEL: 1000 mg/kg bw/day (OECD TG 422, Read Across from Undecanal)	NOAEL: 1000 mg/kg bw/day (OECD TG 422)

For testing data, see the IUCLID under the relevant endpoint.

Justification for classification or non-classification

Based on the available data, the substance does not need to be classified for acute oral, dermal and inhalation toxicity in accordance with the criteria outlined in the EU CLP Regulation (EC No. 1272/2008 and its updates).