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Diss Factsheets

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
The members of the category are all alcohol esters of dicarboxylic acids. All category members are manufactured by reacting an alcohol (methanol, butanol or isobutanol) with single dicarboxylic acids, succinic, glutaric or adipic acids or mixtures of these acids. The ester bonds are effectively metabolised by the body releasing the component alcohols and acids. The difference between members involves 3 parameters: 1) the alcohol used to esterify the acids, 2) the length of the acid molecule (4C, 5C or 6C) and 3) the presence of individual esters or mixtures thereof.

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL
The toxicity profile of the members (ecotoxicity and human health toxicity and the environmental fate) is consistent. All have low acute toxicity potential, are not sensitising, are mildly irritating to eyes and upper respiratory tract (where vapour pressure allows exposure), are not genotoxic or clastogenic (in vivo) and have minimal systemic toxicity. Data are available predominantly for the methyl esters (individual and mixture), dibutyl adipate and diisobutyl esters (mixture). Within the category, read across is used to cover the higher tier human health toxicity studies predominantly.

See attached document with the justification for the category/read-across approach.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1981

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Test material dosed into right eye of 2 rabbits. 20 seconds after treatment one treated eye was washed. Observations of cornea, iris and conjunctiva made at 1 and 4 hours and 1, 2, 3, 7 and 15 days post treatment.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Reaction mass of bis(2-methylpropyl) pentanedioate and bis(2-methylpropyl) butanedioate and bis(2-methylpropyl) hexanedioate
IUPAC Name:
Reaction mass of bis(2-methylpropyl) pentanedioate and bis(2-methylpropyl) butanedioate and bis(2-methylpropyl) hexanedioate
Constituent 2
Chemical structure
Reference substance name:
907-870-9
EC Number:
907-870-9
Molecular formula:
Diisobutyl succinate: C12O4H22 Diisobutyl glutarate: C13O4H24 Diisobutyl adipate: C14O4H26
IUPAC Name:
907-870-9
Details on test material:
34% diisobutyl succinate
55% diisobutyl glutarate
11% diisobutyl adipate
Overall purity >99.9%

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
1 rabbit - 20 seconds
1 rabbit - 1 minute
Observation period (in vivo):
1h, 4h, 1, 2, 3, 7 and 15 days
Number of animals or in vitro replicates:
2 (males)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
uwashed eye
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 15 days
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
7 d
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 15 days
Remarks on result:
probability of mild irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
14 d
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 15 days
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
7 d
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 15 days
Remarks on result:
probability of mild irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 15 days
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 3 days
Remarks on result:
not measured/tested
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 3 days
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 3 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 3 days
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
washed eye
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 2 days
Remarks on result:
probability of weak irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
washed eye
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 2 days
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
washed eye
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 2 days
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
washed eye
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 1 day
Remarks on result:
probability of mild irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
washed eye
Time point:
other: 4 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 2 days
Remarks on result:
probability of weak irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
unwashed eye
Time point:
24 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 2 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
unwashed eye
Time point:
48 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: one day
Remarks on result:
no indication of irritation

Any other information on results incl. tables

Unwashed eye:

Cornea: some slight clouding at 1h, 4h and 3 -7 days. Small area of slight clouding at days 1 and 2. No effects apparent at 15 days

Iris: Slight swelling at days 2 -3 only

Conjunctiva: mild redness at day 1 only; slight swelling at 4 hrs and day 1; mild discharge at 4 hr and 3 days

All effects resolved by day 7 or 15.

Washed eye:

Cornea: local area of slight clouding at 1hr and 1 day only

Iris: No effects

Conjunctiva: No redness, Slight swelling at 1 and 4 hours; mild discharge at 4 hours only

Overall there were minimal signs of irritation in each animal. These effects do not appear to be significant or sufficiently severe to warrant classification for eye irritation.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Conclusions:
Although signs of mild irritation were observed they appear to be slight/mild and do not appear to meet the criteria for classification as irritating to the eyes.
Executive summary:

1/10 ml of undiluted material dosed to the conjunctival sac of the right eye of each of two rabbits. At 20s after dosing the treated eye of one rabbit was washed with tap water for 1 minute. The treated eye of the second rabbit remained unwashed. Observations of the cornea, iris and conjunctiva were made as indicated above. Draize scoring was not used, instead the effects were marked qualititatively. Although signs of mild irritation were observed they appear to be slight/mild and do not appear to meet the criteria for classification as irritating to the eyes.