3,7-dimethyl-1-octyl acetate

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of the given test chemical was determined in various studies conducted on rabbits and human. Based on the available studies, it can be concluded that the test chemical is unable to cause skin irritation and thus it cannot be classified as per CLP regulation.

 

Eye irritation

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not irritating to eyes. Thus, it cannot be classified as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journal.

Qualifier:

according to guideline

Guideline:

other: as per mentioned below

Principles of method if other than guideline:

To assess the dermal irritation potential of the given test chemical in humans.

GLP compliance:

no

Specific details on test material used for the study:

Name of test material (as cited in study report): Dihydrocitronellyl acetate
IUPAC name: 3,7-dimethyl-1-octyl acetate
Molecular formula: C12H24O2
Molecular weight: 200.32 g/mol
Smiles notation: C([C@@H](CCOC(C)=O)C)CCC(C)C
InChl: 1S/C12H24O2/c110(2)65711(3)891412(v4)13/h1011H,59H2,14H3
Substance Type: Organic
Physical State: Liquid

Species:

other: humans

Strain:

not specified

Details on test animals or test system and environmental conditions:

No data available

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

other: Petrolatum

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 8% in Petrolatum

Duration of treatment / exposure:

48 hours

Observation period:

48 hours

Number of animals:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

not irritating

Other effects:

No data available

Interpretation of results:

other: not irritating

Conclusions:

The given test chemical was considered to be not irritating to humans after 48 hours exposure.

Executive summary:

A skin irritation study was performed by using the given test chemical in humans to assess the irritation potential. Test chemical was tested 8% in petrolatum on human volunteers in a 48 hours closed patch test. No indication of irritation was observed. Hence, the given test chemical was considered to be not irritating to humans after 48 hours exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Weight of evidence approach based on various test chemicals

Justification for type of information:

Weight of evidence approach based on various test chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: Weight of evidence approach based on various test chemicals

Principles of method if other than guideline:

WoE report is based on 2 studies as - WoE 2 and WoE 3.

GLP compliance:

not specified

Species:

rabbit

Strain:

other: 2. not specified 3. New Zealand White

Details on test animals or tissues and environmental conditions:

2. no data available
3. no data

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

2. 0.5 ml
3. 0.1 ml

Duration of treatment / exposure:

2. no data available
3. single instillation

Observation period (in vivo):

2. no data available
3. Observations were made after 1 hour, 4 hours and then 1,2,3 and 7 days after instillation of test chemical

Duration of post- treatment incubation (in vitro):

2. no data available
3. No data available

Number of animals or in vitro replicates:

2. no data available
3. 4 rabbits

Details on study design:

2. TEST SITE
Area of exposure: eye
% coverage: No data
Type of wrap if used: no wrap used

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

SCORING SYSTEM:
Grade 1 indicates at most a very small area of necrosis resulting from 0.5 ml of undiluted chemical in the eye. Grade 5 indicates a so-called severe burn from 0.005 ml, and Grade 10 indicates a severe burn from 0.5 ml of a 1% solution in water or propylene glycol
3. TEST SITE
- Area of exposure: conjunctival sac

SCORING SYSTEM: According to the Draize method
Grading Scale for Eye Irritation:
Cornea Grade
Opacity: degree of density (readings should be taken from most dense area)*
No ulceration or opacity = 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris slightly obscured = 1
Easily discernible translucent area; details of iris slightly obscured = 2
Opalescent area; no details of iris visible; size of pupil barely discernible = 3
Opaque cornea; iris not discernible through the opacity = 4
Iris
Normal = 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia; or injection; iris reactive to light (a sluggish reaction is considered to be an effect = 1
Hemorrhage, gross destruction, or no reaction to light = 2
Maximum possible: 2
Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae; excluding cornea and iris)
Vessels Normal = 0
Vessels definitely injected above normal = 1
Diffuse, crimson colour; individual vessels not easily discernible = 2
Diffuse beefy red = 3
Chemosis
Swelling (refers to lids and/or nictating membranes)
Normal = 0
Any swelling above normal (includes nictating membrane)= 1
Obvious swelling, with partial eversion of lids = 2
Swelling, with lids about half closed = 3
Swelling, with lids more than half closed= 4

Overall Maximum Possible Score = 110

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: no data available

Score:

1

Max. score:

10

Reversibility:

not specified

Remarks on result:

no indication of irritation

Remarks:

2

Irritation parameter:

other: Modified Maximum Average Score

Basis:

mean

Time point:

other: 1 days

Score:

7.5

Max. score:

110

Reversibility:

fully reversible

Remarks:

7 days

Remarks on result:

other: Conjunctival redness and chemosis was observed in all animals after 1 day of observation

Remarks:

3

Irritation parameter:

other: Modified Maximum Average Score

Basis:

mean

Time point:

other: 7 days

Score:

0

Max. score:

110

Reversibility:

not specified

Remarks on result:

other: no effects observed

Remarks:

3

Irritant / corrosive response data:

2. No irritation observed
3. Conjunctival redness and chemosis was observed in all animals after 1 day of observation

Interpretation of results:

other: not irritating

Conclusions:

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not irritating to eyes. Thus it can be further classified under the category “Not Classified” as per CLP regulation.

Executive summary:

The ocular irritation potential was assessed based on the available results from the various test chemicals.These studies have been summarized as below -

 

An eye irritation study was carried out by using the given test chemical to evaluate the irritation potential. 0.5 ml of undiluted chemical was instilled into the eye of rabbits. Observations were made after instillation of test chemical. Eye injury in rabbits was recorded in a 10- grade ordinal series and was based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical. Primary Eye Irritation score after 24 hours for the given test chemical was Grade 1. Based on the grade, it was considered to be not irritating to eyes.

 

The above study is supported by the results of an eye irritation study conducted to evaluate the irritant nature of the test chemical in rabbits as per OECD 405 “EYE IRRITATION”. 0.1 ml of the test chemical was instilled into the conjunctival sac of 4 New Zealand White rabbits. Observations were made after 1 hour, 4 hours and then 1, 2, 3 and 7 days after instillation of test chemical. The scoring was done according to the Draize method. Conjunctival redness and chemosis was observed in all animals after 1 day of observation. The MMAS (Maximum Modified Average Score) of the given test chemical was 7.5 after 1 day of observation. The effects were recovered fully after 7 days and the MMAS scores were 0.0. Based on the classification of chemicals according to MMAS scores, test chemical can be considered to be not irritating to rabbit eyes.

 

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not irritating to eyes. Thus, it cannot be classified as per CLP regulation.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

In different studies, the given test chemical has been investigated for the dermal irritation potential to a greater or lesser extent. The studies are based on in-vivo experiments conducted in humans and rabbits that have been summarized as below -

 

A skin irritation study was performed by using the given test chemical in humans to assess the irritation potential. Test chemical was tested 8% in petrolatum on human volunteers in a 48 hours closed patch test. No indication of irritation was observed. Hence, the given test chemical was considered to be not irritating to humans after 48 hours exposure.

 

The above study is supported with another skin irritation study performed in rabbits to assess the irritation potential. Undiluted test chemical was applied under occlusion to the intact and abraded skin of rabbits for 24 hours. The rabbits were observed for signs of irritation. Slight to moderate irritation was observed to rabbit skin, Hence, the given test chemical was considered to be slightly to moderately irritating to rabbit skin after 24 hours exposure.

 

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for the given test chemical. Based on estimation, no severe skin irritation effects were known when the given test chemical was exposed to rabbit skin. Hence, it can be considered as not irritating to skin.

 

The estimated data is supported by another skin irritation study performed in rabbits to assess the irritation potential. Undiluted test chemical was applied under occlusion to the intact and abraded skin in rabbits for 24 hours. The rabbits were observed for signs of irritation. No irritation was observed. Hence, the given test chemical was considered to be not irritating to rabbit skin after 24 hours exposure.

 

The above study is supported with the study performed in humans to assess the irritation potential by using the given test chemical. The chemical was applied as 2% in petrolatum and tested on human volunteers in a 48 hours closed patch test. The volunteers were observed for signs of irritation. No irritation observed. Hence, the given test chemical was considered to be not irritating to human skin after 48 hours exposure.

 

All the above results are further supported with the skin irritation study conducted on rabbits to determine the degree of skin irritancy of the given test chemical. Each rabbit received neat chemical on intact or abraded skin for 24 hours under occlusive condition and later observed for skin lesions. Since the treated rabbits showed no signs of irritation, the given test chemical was considered to be not irritating to the intact or abraded skin of rabbits.

 

Even though the results of study on rabbits indicate a possibility of the test chemical being irritating to skin, but the remaining studies suggest otherwise. Also, the estimation on skin irritation effects due to the test chemical indicates a negative effect. Taking into consideration, all these parameters, the test chemical can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP Regulation, the given test chemical cannot be classified for “Skin Irritation”.

 

Eye irritation

The ocular irritation potential was assessed based on the available results from the various test chemicals.These studies have been summarized as below -

 

An eye irritation study was carried out by using the given test chemical to evaluate the irritation potential. 0.5 ml of undiluted chemical was instilled into the eye of rabbits. Observations were made after instillation of test chemical. Eye injury in rabbits was recorded in a 10- grade ordinal series and was based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical. Primary Eye Irritation score after 24 hours for the given test chemical was Grade 1. Based on the grade, it was considered to be not irritating to eyes.

 

The above study is supported by the results of an eye irritation study conducted to evaluate the irritant nature of the test chemical in rabbits as per OECD 405 “EYE IRRITATION”. 0.1 ml of the test chemical was instilled into the conjunctival sac of 4 New Zealand White rabbits. Observations were made after 1 hour, 4 hours and then 1, 2, 3 and 7 days after instillation of test chemical. The scoring was done according to the Draize method. Conjunctival redness and chemosis was observed in all animals after 1 day of observation. The MMAS (Maximum Modified Average Score) of the given test chemical was 7.5 after 1 day of observation. The effects were recovered fully after 7 days and the MMAS scores were 0.0. Based on the classification of chemicals according to MMAS scores, test chemical can be considered to be not irritating to rabbit eyes.

 

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not irritating to eyes. Thus, it cannot be classified as per CLP regulation.

 

Justification for classification or non-classification

Even though the results of study on rabbits indicate a possibility of the test chemical being irritating to skin, but the remaining studies suggest otherwise. Also, the estimation on skin irritation effects due to the test chemical indicates a negative effect. Taking into consideration, all these parameters, the test chemical can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP Regulation, the given test chemical cannot be classified for “Skin Irritation”.

 

Based on the available data for the various test chemicals and applying the weight of evidence approach, it can be concluded that the test chemical will also behave in similar manner and was estimated to be not irritating to eyes. Thus, it cannot be classified as per CLP regulation.