5-methyl-5-phenylhexan-3-one

Endpoint summary

Description of key information

Acute oral toxicity using read across from Vetikon (OECD TG 401): LD50 >2000 mg/kg bw

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:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 7 December 1994 and 27 December 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Reliability 2 is assigned because the study was used for read-across.

Justification for type of information:

The present information is used for read across to Damascol.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

February 24, 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

July 31, 1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Hsd/Win: WU

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Fa. Harlan Winkelmann GmbH
- Age at study initiation: no information available
- Weight at study initiation: males: 201-237 g, females: 177-203 g
- Fasting period before study: ~16 h
- Housing: collective housing up to a maximum of 5 animals per cage (Makrolon type III)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±3
- Humidity (%): 30-70
- Air changes (per hr): no information available
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.02 mL/kg (for 2000 mg/kg bw dose)

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were observed 10 minutes, 1, 2 and 6 hours after application and thereafter daily
- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed by CO2 asphyxiation, necropsied and subjected to examination for gross pathological changes.
- Body weights: Individual body weights were recorded immediately before treatment (day 1) and then on the 7th and 14th day of the observation period.

Preliminary study:

None of the animals died in the preliminary study.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the course of the main study.

Clinical signs:

In some animals abnormal clinical signs were observed up to 24 hours after administration of the test substance. These signs included abnormal gait, squatting position, reduced activity, piloerection and decreased respiratory rate.

Body weight:

No treatment related changes were recorded in the body weights of the animals during the study period.

Gross pathology:

No abnormalities observed.

Interpretation of results:

other: not classified for actute oral toxicity

Remarks:

Based on CLP criteria (EC 1272/2008 and its amendments)

Conclusions:

The acute oral LD50 for Vetikon in male and female rats was determined to be >2000 mg/kg bw. Based on this result, the test material does not need to be classified for acute oral toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Executive summary:

In this study, 10 rats (5 males and 5 females) were administered Vetikon at a single dose level of 2000 mg/kg bw by oral gavage. The study was performed according to OECD guideline 401. A preliminary study was conducted with 2 female rats for range finding; in this study there were no deaths recorded. During the main study there were also no mortalities recorded. Clinical signs were observed up to 24 hours after administration. These effects included abnormal gait, squatting position, reduced activity, piloerection and decreased respiratory rate. No body weight or gross pathology abnormalities were detected. The acute oral LD50 for Vetikon in male and female rats was determined to be >2000 mg/kg bw. Based on this result, Vetikon does not need to be classified for acute oral toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

The acute oral toxicity of Damascol using read across from Vetikon
Introduction and hypothesis for the analogue approach
Damascol is a ketone, specifically an ethyl phenyl (dimethyl)ethyl ketone. For this substance no acute oral toxicity data are available.
In accordance with Article 13 of REACH, lacking information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the acute oral toxicity of Damascol the analogue approach is selected because for one closely related analogue acute oral toxicity information is available, which can be used for read across.
Hypothesis: Damascol has similar acute oral toxicity compared to Vetikon resulting in a similar LD50 because the additional methyl in Damascol does not affect the organ toxicity and the LD50.
Available information: The source chemical Vetikon has been tested in a well conducted acute oral toxicity test (method according to OECD TG 401 under GLP) up to 2000 mg/kg bw and the test result receives a reliability of 1 for the test as such.
Target chemical and source chemical(s)
Chemical structures of the target and the source chemicals are shown in Appendix 1, including physico-chemical properties and toxicological information, thought relevant for acute oral toxicity, of source and target substances.
Purity / Impurities
The purity and impurities of the target substance do not indicate acute oral toxicity potential other than indicated by the parent substance. The impurities are all below < 10%.
Analogue approach justification
According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation.
Analogue selection: According to ECHA guidance (RAAF, 2015) a clear documentation is needed on the selection of potential source substances. Vetikon is selected as a suitable analogue differing only in one methyl group for which acute oral toxicity information is available.
Structural similarities and differences: The target and the source chemicals have a similar backbone (3-phenylpentanone vs. 2-phenylbutanone) and functional group (ketone), and differ in an additional methyl group adjacent to the carbonyl carbon (i.e., ethyl vs. methyl substituent) in the target. This additional methyl groups differences between the target and source chemicals are not expected to result in different behaviour to the target organs, because the additional methyl not expected to influence significantly the acute oral toxicity of these chemicals.
Toxicokinetic: The source chemicals and the target chemicals indicate similar toxico-kinetic characteristics based on the similarity in chemical structure molecular weight and appearance as well as similarities in physico-chemical properties. The metabolism processes are similar, with a likely transformation involving reduction of the ketone to the corresponding alcohol, which can be excreted via urine after phase 2 conjugation. There are no significant differences in rates to be expected.
Toxico-dynamic: In view of the similarities presented above no differences in toxico-dynamics features are anticipated for acute oral toxicity: the substances are considered to have limited reactive features based on a sole ketone in the aliphatic chain.
Uncertainty of the prediction: There are no remaining uncertainties, based on arguments presented above.
In the ECHA guidance (RAAF, 2015) terminology it receives a score of 5 (acceptable with high confidence), because the rationale for the selection of the analogues is clearly presented.
Data matrix
The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data Matrix below.
Conclusions per endpoint for C&L
When using read across the result derived should be applicable for C&L and/or risk assessment, cover an exposure period duration comparable or longer than the corresponding method and be presented with adequate and reliable documentation. For Vetikon a well conducted acute oral toxicity test is available (Reliability 1) with a LD50 of >2000 mg/kg bw which leads to absence of classification for this endpoint. Based on these data for Damascol also a LD50 of >2000 mg/kg bw (Reliability 2 based on read across) can be derived for the acute oral toxicity endpoint and therefore it is not classified.
Final conclusion on hazard, C&L: Damascol has a LD50 of >2000 mg/kg bw and therefore does not need to be classified and labelled for this endpoint according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 and its updates.

Data matrix with information on Damascol and analogue important for assessment of acute oral toxicity
Common name Damascol Vetikon
CAS 4927-36-0 7403-42-1
Chemical structures
Empirical formula C13H18O C12H16O
Physico-chemical data
Molecular weight 190.29 176.26
Appearance Liquid Liquid
Vapour pressure at 25˚C (Pa) (EpiSuite) 1.98 (measured) 3.72 (EpiSuite)
Water solubility at 20˚C (mg/L) 95 (measured) 179-217 (EpiSuite)
Log Kow (Episuite) 3.5 (measured) 2.84
Human health endpoints
Acute oral tox in mg/kg bw Read across LD50 >2000

Reason / purpose for cross-reference:

read-across source

Preliminary study:

None of the animals died in the preliminary study.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No animals died during the course of the main study.

Clinical signs:

In some animals abnormal clinical signs were observed up to 24 hours after administration of the test substance. These signs included abnormal gait, squatting position, reduced activity, piloerection and decreased respiratory rate.

Body weight:

No treatment related changes were recorded in the body weights of the animals during the study period.

Gross pathology:

No abnormalities observed.

Interpretation of results:

other: not classified for acute oral toxicity

Remarks:

Based on CLP criteria (EC 1272/2008 and its amendments)

Conclusions:

The acute oral LD50 for Vetikon in male and female rats was determined to be >2000 mg/kg bw. Based on this result, the test material does not need to be classified for acute oral toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC). This result was read-across to Damascol 4.

Executive summary:

In this study, 10 rats (5 males and 5 females) were administered Vetikon at a single dose level of 2000 mg/kg bw by oral gavage. The study was performed according to OECD guideline 401 and is used for read-across to Damascol 4. A preliminary study was conducted with 2 female rats for range finding; in this study there were no deaths recorded. During the main study there were also no mortalities recorded. Clinical signs were observed up to 24 hours after administration. These effects included abnormal gait, squatting position, reduced activity, piloerection and decreased respiratory rate. No body weight or gross pathology abnormalities were detected. The acute oral LD50 for Vetikon in male and female rats was determined to be >2000 mg/kg bw. Based on this result, Vetikon does not need to be classified for acute oral toxicity in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC). This result was read-across to Damascol 4.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The acute oral toxicity result is of sufficient quality and adequate for this dossier.

Additional information

The acute toxicity of Damascol is derived based on read across from Vetikon. First the experimental information of Vetikon is provided and thereafter the read across justification.

Vetikon acute oral toxicity

In the key study, 10 rats (5 males and 5 females) were administered Vetikon at a single dose level of 2000 mg/kg bw by oral gavage. The study was performed according to OECD guideline 401 and is used for read-across to Damascol. A preliminary study was conducted with 2 female rats for range finding; in this study there were no deaths recorded. During the main study there were also no mortalities recorded. Clinical signs were observed up to 24 hours after administration. These effects included abnormal gait, squatting position, reduced activity, piloerection and decreased respiratory rate. No body weight or gross pathology abnormalities were detected. The acute oral LD50 for Vetikon in male and female rats was determined to be >2000 mg/kg bw.

The acute oral toxicity of Damascol using read across from Vetikon

Introduction and hypothesis for the analogue approach

Damascol is a ketone, specifically an ethyl phenyl (dimethyl)ethyl ketone. For this substance no acute oral toxicity data are available.

In accordance with Article 13 of REACH, lacking information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. For assessing the acute oral toxicity of Damascol the analogue approach is selected because for one closely related analogue acute oral toxicity information is available, which can be used for read across.

Hypothesis: Damascol has similar acute oral toxicity compared to Vetikon resulting in a similar LD50 because the additional methyl in Damascol does not affect the organ toxicity and the LD50.

Available information: The source chemical Vetikon has been tested in a well conducted acute oral toxicity test (method according to OECD TG 401 under GLP) up to 2000 mg/kg bw and the test result receives a reliability of 1 for the test as such.

Target chemical and source chemical(s)

Chemical structures of the target and the source chemicals are shown in Appendix 1, including physico-chemical properties and toxicological information, thought relevant for acute oral toxicity, of source and target substances.

Purity / Impurities

The purity and impurities of the target substance do not indicate acute oral toxicity potential other than indicated by the parent substance. The impurities are all below < 10%.

Analogue approach justification

According to Annex XI 1.5 read across can be used to replace testing when the similarity can be based on a common backbone and a common functional group. When using read across the result derived should be applicable for C&L and/or risk assessment and it should be presented with adequate and reliable documentation.

Analogue selection:According to ECHA guidance (RAAF, 2015) a clear documentation is needed on the selection of potential source substances. Vetikon is selected as a suitable analogue differing only in one methyl group for which acute oral toxicity information is available.

Structural similarities and differences:The target and the source chemicals have a similar backbone (3-phenylpentanone vs. 2-phenylbutanone) and functional group (ketone), and differ in an additional methyl group adjacent to the carbonyl carbon (i.e., ethyl vs. methyl substituent) in the target. This additional methyl groups differences between the target and source chemicals are not expected to result in different behaviour to the target organs, because the additional methyl not expected to influence significantly the acute oral toxicity of thesechemicals.

Toxicokinetic:The source chemicals and the target chemicals indicate similar toxico-kinetic characteristics based on the similarity in chemical structure molecular weight and appearance as well as similarities in physico-chemical properties.The metabolism processes are similar, with a likely transformation involving reduction of the ketone to the corresponding alcohol, which can be excreted via urine after phase 2 conjugation. There are no significant differences in rates to be expected.

Toxico-dynamic: In view of the similarities presented above no differences in toxico-dynamics features are anticipated for acute oral toxicity: the substances are considered to have limited reactive features based on a sole ketone in the aliphatic chain.

Uncertainty of the prediction:There are no remaining uncertainties, based on arguments presented above.

In the ECHA guidance (RAAF, 2015) terminology it receives a score of 5 (acceptable with high confidence), because therationale for the selection of the analogues is clearly presented.

Data matrix

The relevant information on physico-chemical properties and toxicological characteristics are presented in the Data Matrix below.

Conclusions per endpoint for C&L

When using read across the result derived should be applicable for C&L and/or risk assessment, cover an exposure period duration comparable or longer than the corresponding method and be presented with adequate and reliable documentation.For Vetikona well conducted acute oral toxicity test is available (Reliability1) with a LD50 of >2000 mg/kg bw which leads to absence of classification for this endpoint. Based on these data forDamascolalso a LD50 of >2000 mg/kg bw (Reliability 2 based on read across) can be derived for the acute oral toxicity endpoint and therefore it is not classified.

Final conclusion on hazard, C&L:Damascol has a LD50 of>2000mg/kg bw and therefore does not need to be classified and labelled for this endpoint according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 and its updates.

 

Data matrix with information on Damascol and analogue important for assessment of acute oral toxicity

Common name	Damascol	Vetikon
CAS	4927-36-0	7403-42-1
Chemical structures
Empirical formula	C13H18O	C12H16O
Physico-chemical data
Molecular weight	190.29	176.26
Appearance	Liquid	Liquid
Vapour pressure at 25˚C (Pa) (EpiSuite)	1.98 (measured)	3.72 (EpiSuite)
Water solubility at 20˚C (mg/L)	95 (measured)	179-217 (EpiSuite)
Log Kow (Episuite)	3.5 (measured)	2.84
Human health endpoints
Acute oral tox in mg/kg bw	Read across	LD50 >2000

 

Justification for classification or non-classification

Damascol does not have to be classified based on information of Vetikon. Based on the result of the key study, the substance does not have to be classified as acute toxic by the oral route in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC and its updates).

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