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Administrative data

Description of key information

Skin irritation : an in vivo study in rabbit ( ECETOC, 1995-KS),and an in vitro study were available in human (Tornier, 2006-SS) are available.
Eye irritaion : A guideline study (Auletta, 1980-OECD 405) was available in rabbits.

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: Secondary literature
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
no
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
Concentration = 100%
Volume tested = 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
4
Details on study design:
no
Irritation parameter:
edema score
Basis:
mean
Remarks:
4 rabbits
Time point:
other: 24-48-72
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: 3 animals have a mean score higher to 2, but 1 animal have a mean score higher to 2.3
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
4 rabbits
Time point:
other: 24/48/72
Score:
5
Max. score:
10.7
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.5
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.5
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.66
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.16
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.5
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.66
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
not fully reversible within: 7 days

Table : Skin irritation data for individual rabbits

Observation interval

1 hour

1 day

2 days

3 days

7 days

Animal no.1

Erythema

1.5

3.5

3.5

3.5

3.5

Oedema

0.5

2

2

2

2

Animal no.2

Erythema

1.5

3.5

3.5

3.5

3.5

Oedema

1.5

2.5

2

1.5

1.5

Animal no.3

Erythema

1

2

3

3

3

Oedema

1

3

2.5

2.5

2

Animal no.4

Erythema

1

2

2

2.5

2.5

Oedema

0.5

1.5

1.5

1.5

2

Interpretation of results:
Category 2 (irritant)
Conclusions:
According this study, heptanal is a skin irritant in rabbits, and is classified in category 2 according to the Regulation (EC) no.1272/2008 (CLP).
Executive summary:

Heptanal was tested on four rabbit at a concentration of 100% during 4 hours. The observation interval was 7 days.

The mean score of erythema was 3 out of 4 (mean of 4 rabbits, and mean of results at 24/48/72 hours).

The mean score of edema was 2 out of 4 (mean of 4 rabbits, and mean of results at 24/48/72 hours).

The effects were not fully reversible at 7 days. A desquamation from the skin was observed in all four rabbits at 7 days.

According this study, heptanal is a skin irritant in rabbits, and is classified in category 2 according to the Regulation (EC) no.1272/2008 (CLP).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 10 November 1980 To 17 November 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2c Comparable to guideline study with acceptable restrictions.
Qualifier:
according to guideline
Guideline:
other: 40 CFR Part 163.81-' (Environmental protection agency pesticide programs. Proposed guidelines for registering pesticides in U.S.; hazard evaluation: humans and domestic animal. Primary eye irritation study)
Deviations:
not specified
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratory Animals, Denver, Pennsylvania.
- Age at study initiation: young adults
- Weight at study initiation: 2.1 to 2.9 kg
- Fasting period before study: no data
- Housing: individual
- Diet : ad libitum, Purina Rabbit chow.
- Water : ad libitum.
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 21
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 10 November 1980 To: 17 November 1980
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml into the lower conjunctival sac of the right eye of each animal.



Duration of treatment / exposure:
The treated and control eyes of six animals remained unwashed.
Twenty seconds after the test substance was administered, both eyes of the remaining three animals were rinsed for one minute with lukewarm water.
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
9 (6 unwashed, 3 rinsed after 20 seconds of exposure)
Details on study design:
REMOVAL OF TEST SUBSTANCE in 3/9 animals
- Washing (if done): lukewarm water
- Time after start of exposure: twenty second


SCORING SYSTEM:
According to the Draize scale


Cornea
Opacity: degree of density (area most dense taken for reading)*
No opacity........................................................................................................................................... 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre);
details of iris clearly visible .............................................................................................................. 1
Easily discernible translucent area; details of iris slightly obscured .........................................2
Nacreous area; no details of iris visible; size of pupil barely discernible ..................................3
Complete corneal opacity; iris not discernible ..............................................................................4
Maximum possible: 4

Iris
Normal......................................................................................................................................................0
Markedly deepened folds, congestion, swelling, circumcorneal injection;
(any of these or combination of any thereof).....................................................................................1
No reaction to light, hemorrhage, gross destruction (any or all of these)....................................2
Maximum possible: 2

Conjunctivae
Redness (refers to palpebral and bulbar conjunctivae; excluding cornea and iris)
Vessels normal ................................................................................................................................0
Some vessels definitely injected ...................................................................................................1
Diffuse, crimson red; individual vessels not easily discernible ...............................................2
Diffuse beefy red..............................................................................................................................3
Maximum possible: 3

Chemosis
Swelling (refers to lids and/or nictating membranes)
No swelling.........................................................................................................................................0
Any swelling above norma (includes nictitating 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
Maximum possible: 4
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
6 rabbits unwashed
Time point:
other: 24, 48 and 72 hours
Score:
1.9
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 2 animals with a score > or = 2
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Remarks:
6 rabbits unwashed
Time point:
other: 24, 48 and 72 hours
Score:
1.55
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 2 animals with a score > or = 2
Irritation parameter:
iris score
Basis:
mean
Remarks:
6 rabbits unwashed
Time point:
other: 24, 48 and 72 hours
Score:
0.5
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 1 animal with a score > or = 1
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Remarks:
6 rabbits unwashed
Time point:
other: 24, 48 and 72 hours
Score:
0.95
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 3 animals with a score > or = 1
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
other: 3 rabbits "washed"
Remarks:
3 rabbits "washed"
Time point:
other: 24-48-72 hours
Score:
2.1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: All 3 animals with a score > or = 2
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Remarks:
3 rabbits "washed"
Time point:
other: 24-48-72 hours
Score:
0.56
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 0 animal with a score > or = 2
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits "washed"
Time point:
other: 24-48-72 hours
Score:
0.2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 0 animal with a score > or = 1
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Remarks:
3 rabbits "washed"
Time point:
other: 24-48-72 hours
Score:
0.1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 0 animals with a score > or = 1
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within:
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
All nine rabbits exhibited positive scores for conjunctival redness, chemosis and necrosis. Four of the six animals with unwashed eyes exhibited positive scores for corneal opacity and ulceration, and five animals had iridial irritation. Two of the three animals with washed eyes showed positive scores for iridial irritation and corneal ulceration, and one exhibited a positive for iridial and corneal ulceration, and one exhibited a positive score for corneal opacity. All eyes were free of irritation by Day 7.
Other effects:
None.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point/ Reversibility  Cornea
Max. score: 4
Iris
Max. score: 2
Conjunctivae
Max. score: 3
Chemosis
Max. score: 4
24 h 2/0/2/2/0/1 1/0/1/1/1/1 2/2/2/3/2/2 2/2/3/3/2/3
48 h 2/0/1/2/0/1 1/0/0/1/0/1 2/2/2/3/2/2 1/1/2/2/1/2
72 h 2/0/0/2/0/0 0/0/0/1/0/0 2/0/1/3/1/1 1/0/1/1/1/0
Days 4 1/0/0/0/0/0 0/0/0/0/0/0 2/0/0/2/0/0 1/0/1/1/1/0
Days 7 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0 0/0/0/0/0/0
Mean scores over 24, 48 and 72 hours for each animal 2/0/1/2/0/0.66 0.66/0/0.33/1/0.33/0.66 2/1.33/1.66/3/1.66/1.66 1.33/1/2/2/1.33/1.66
Average 24h, 48h, 72h calculated over all the animal tested 0.94 0.5 1.88 1.55
Reversibility*) c. c. c. c.

*) Reversibility: c.=completely reversible; n.c.= not completely reversible; n= not reversible0

Interpretation of results:
slightly irritating
Remarks:
Migrated information but not classified Criteria used for interpretation of results: other: CLP regulation
Conclusions:
Under the conditions of this test, the substance is considered as slightly irritating and is not classified according to EU and CLP classification.
Executive summary:

In an ocular irritation test (Bio/dynamics Inc., 1980), nine albino New Zealand white rabbits were used. The test substance (heptanal) was introduced into the lower conjunctival sac of the right eye of each animal. The animal's left eye served as a control. The treated and control eyes of six animals (3 females and 3 males) remained unwashed. Twenty seconds after the test substance was administered, both eyes of the remaining three animals (2 females and 1 male) were rinsed for one minute with lukewarm water. Animals were observed for 7 days. Irritation was scored following a grading of ocular lesions similar to that of the guideline OECD 405. After 24 hours all rabbits (washed and unwashed) showed chaemosis and redness reactions. Most of these effects decreased after 24 hr and desappeared totally after 4 or 7 days. Iris and corneal reactions were also reported in some animals (washed and unwashed). The scores (mean: 24, 48 and 72 hr scores) calculated over all the unwashed animal tested for chemosis, redness of conjunctivae, iris lesion and cornea opacity were respectively 1.55, 1.88, 0.5 and 0.94. Eye observed reactions were fully reversible within 4 or 7 days in all animals. Under the conditions of this test, the tested substance is considered as slightly irritating and is not classified according to EU and CLP classification.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation:

Heptanal was tested on four rabbits at a concentration of 100% during 4 hours (ECETOC 1995). The observation interval was 7 days. The mean score of erythema was 3 out of 4 (mean of 4 rabbits, and mean of results at 24/48/72 hours).

The mean edema score was 2 out of 4 (mean of 4 rabbits, and mean of results at 24/48/72 hours).

The effects were not fully reversible at 7 days. A desquamation from the skin was observed in all four rabbits at 7 days.

According this study, heptanal is a skin irritant in rabbits, and is classified in category 2 according to the Regulation (EC) no.1272/2008 (CLP).

In an in vitro skin irritation study on reconstituted human epidermis (Tornier 2006), the irritant potential of Heptanal was tested using two in vitro protocols. One is a direct topical application test and the other an in vitro patch test. Both protocols were performed using multiple endpoint analysis including cell viability (MTT reduction), histology, and IL-1alpha release. In both in vitro tests, Heptanal induced low cell viability, necrosed histology and increase of the amount of IL-1alpha. Therefore, under the conditions of this test, Heptanal was considered as a skin irritant. Moreover, considering results obtained with a 28-day dermal toxicity study, irritation induced by heptanal could be considered as reversible.

Eye irritation:

In an ocular irritation test (Auletta, 1980), nine albino New Zealand white rabbits were used. The test substance (heptanal) was introduced into the lower conjunctival sac of the right eye of each animal. The animal's left eye served as a control. The treated and control eyes of six animals (3 females and 3 males) remained unwashed. Twenty seconds after the test substance was administered, both eyes of the remaining three animals (2 females and 1 male) were rinsed for one minute with lukewarm water. Animals were observed for 7 days. Irritation was scored following a grading of ocular lesions similar to that of the guideline OECD 405. After 24 hours all rabbits (washed and unwashed) showed chaemosis and redness reactions. Most of these effects decreased after 24 hr and desappeared totally after 7 days. Iris and corneal reactions were also reported in some animals (washed and unwashed). The scores (mean: 24, 48 and 72 hr scores) calculated over all the unwashed animal tested for chemosis, redness of conjunctivae, iris lesion and cornea opacity. Eye observed reactions were fully reversible within 7 days in all animals. Under the conditions of this test, the tested substance is considered as slightly irritating for the eyes.

Justification for classification or non-classification

According to regulation (EC/CLP) no 1272 -2008:

  • Skin irritation : classified skin irritant in category 2 according to CLP, irritation was observed in vivo and in vitro.
  • Eye irritation : not classified, mean scoring value for corneal opacity or iritis was beneath 1 and conjunctival redness or conjunctival oedema was beneath 2. Moreover, the observed slight irritation was fully reversible within 7 days.

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