3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate

Endpoint summary

Description of key information

Skin, OECD 404, rabbit: not irritating
Eye, OECD 405, rabbit: not irritating

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. The exposure time was 24 h, no experimental 48 h reading performed, occlusive exposure, the analytical purity of the test substance was not specified.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

24 h exposure time, no experimental 48 h reading, occlusive exposure

GLP compliance:

not specified

Species:

rabbit

Strain:

other: New Zealand

Type of coverage:

occlusive

Preparation of test site:

other: shaved and abraded

Vehicle:

unchanged (no vehicle)

Controls:

other: not required, untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

24 h

Observation period:

72 h
Reading time points: 24 and 72 h

Number of animals:

6 males

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

ca. 0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: No 48 h values are available: for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: No 48 h values are available: for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Remarks:

: for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects seen at 24 h over 48 h)

Irritant / corrosive response data:

Intact skin:
In 6/6 rabbits, very slight to well defined erythema was noted at the 24-hour reading time point (score 1-2). The skin irritation effects were completely reversible within 72 h. No edema was observed in any animal.

Abraded skin:
In 6/6 rabbits, very slight to well defined erythema was noted at the 24-hour reading time point (score 1-2). The skin irritation effects were completely reversible within 72 h. No edema was observed in any animal.

Table 1. Results of skin irritation study – intact skin

Observation time	Rabbit no.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
24 h	2	0	1	0	1	0	1	0	1	0	1	0
48 h	No experimental values available;for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption)
72 h	0	0	0	0	0	0	0	0	0	0	0	0

 

Table 2. Calculation of mean scores

	Rabbit no.
	1		2		3		4		5		6
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
Mean value 24 + 48 + 72 h*	1.33	0.00	0.67	0.00	0.67	0.00	0.67	0.00	0.67	0.00	0.67	0.00

* No 48 h values are available: for calculation of mean scores, the 48 h values were assumed to be the same as those at 24 h (worst case assumption: persistence of effects over 24 h and 48 h)

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

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:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given. No details on study protocol given; the analytical purity of the test substance is not specified.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no details on study protocol; analytical purity of the test substance not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

other: not required

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

72 h
Reading time points: 1, 24, 48 and 72 h and 7 days

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 1.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0.67

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

3/3 rabbits had some or obvious chemosis and severe redness (conjunctivae, score 3 of 3) at the 1-hour reading time point (see Table 1). 24 hours after instillation of the test substance, 1/3 rabbits still exhibited some chemosis, which had cleared completely within 48 hours. The severity of the redness was slightly reduced in 2/3 rabbits and remained unchanged in 1/3 rabbits at the 24-hour reading time point. The chemosis was completely reversible within 72 hours. No effects on the cornea or iris were noted at any time point.

Table 1: individual irritation scores

 

Rabbit #	Time	conjunctivae		iris	cornea
		redness	chemosis
1	1 h	3	1	0	0
	24 h	3	0	0	0
	48 h	2	0	0	0
	72 h	0	0	0	0
	Average*	1.67	0.0	0.0	0.0
2	1 h	3	1	0	0
	24 h	2	0	0	0
	48 h	0	0	0	0
	72 h	0	0	0	0
	Average*	0.67	0.0	0.0	0.0
3	1 h	3	2	0	0
	24 h	2	1	0	0
	48 h	1	0	0	0
	72 h	0	0	0	0
	Average*	1.00	0.33	0.0	0.0

* mean of 24 + 48 + 72 h

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

 

CAS 59219-71-5

A skin irritation study was performed with 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate (CAS 59219-71-5) according to a protocol similar to OECD guideline 404 (Masson, 1986). The shaved skin of 6 rabbits was exposed to 0.5 mL undiluted test material for 24 hours under occlusive conditions. The skin irritation effects were evaluated 24 and 72 hours after patch removal. At the 24-hour reading time point, very slight erythema (score 1) was noted in 5/6 rabbits and well-defined erythema (score 2) in 1/6 rabbits, respectively. All skin irritation effects had cleared completely within 72 hours after the exposure ended. The mean erythema scores (over 24, 48 and 72 hours) per animal were 1.33, 0.67, 0.67, 0.67, 0.67 and 0.67, respectively. No edema was observed in any animal, leading to mean edema scores (over 24, 48 and 72 hours) of 0. The test substance is not considered to be irritating to the skin.

Eye irritation

 

CAS 59219-71-5

An acute eye irritation study was performed with 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate (CAS 59219-71-5) according to a protocol similar to OECD guideline 405 (Dufour, 1990). 0.1 mL of the test substance was instilled into the eyes of 3 New Zealand White rabbits. The animals were observed for 72 hours and scoring was performed 1, 24, 48 and 72 h after instillation. 3/3 rabbits had slight to moderate chemosis (score 1 – 2) and severe redness (conjunctivae, score 3) at the 1-hour reading time point. At the 24-hour reading time point 1/3 rabbits had slight chemosis (score 1). The redness had reduced in severity 24 and 48 hours after instillation, and cleared completely within the 72-hour reading time point. The mean chemosis scores were 0, 0 and 0.33, respectively, and the effect was completely reversible within 48 hours. The conjunctivae mean scores were 1.67, 0.67 and 1.00, respectively. No effects on the cornea or iris were noted in any animal at any time point. The test substance is not considered to be irritating to the eye.

Overall conclusion for skin and eye irritation

The available data on 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate did not show skin or eye irritation effects. Therefore, 3,5,5-trimethylhexyl 3,5,5-trimethylhexanoate is not considered to be a skin irritant or an eye irritant.

Justification for selection of skin irritation / corrosion endpoint:
The key study was selected.

Justification for selection of eye irritation endpoint:
The key study was selected.

Justification for classification or non-classification

The available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.