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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 4 april 1994 to 10 june 1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2c: Comparable to guideline study (OECD 404) with acceptable restrictions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Heptanoic acid
EC Number:
203-838-7
EC Name:
Heptanoic acid
Cas Number:
111-14-8
Molecular formula:
C7H14O2
IUPAC Name:
heptanoic acid
Details on test material:
- Name of test material (as cited in study report): n-heptanoic acid
- Substance type: carboxylic acid
- Physical state: liquid
- Analytical purity: 99.4 %
- Purity test date: 8 february 1994
- Lot/batch No.: 94017-1
- Expiration date of the lot/batch: july 1994
- Storage condition of test material: storage in cool area and in container closed

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc. Denver, Pennsylvania
- Age at study initiation: young adult
- Weight at study initiation: 2788 to 3403 grams at study initiation
- Housing: individually in suspended wire-mesh cages
- Diet : ad libitum (Purina certified rabbit chow)
- Water : ad libitum (tap water)
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature : 20-22 °C (68-72°F)
- Humidity (%): 38-66
- Air changes (per hr): no data
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: from 4 april 1994 to 10 june 1994

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied : 0.5 ml
Duration of treatment / exposure:
3 minutes and 60 minutes.
Observation period:
48 hours
Number of animals:
8 (5 males and 3 females)
Details on study design:
TEST SITE
- Area of exposure: the backs of the rabbits
- % coverage: no data
- Type of wrap if used: a secured 2-ply, 2.5 cm x 2.5 cm gauze patch, that was overwrapped with plastic wrap and secured with Dermiform Tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The sites were wiped with disposable paper towels moistened with tepid water after collection of the initial observations for the presence/absence of corrosion.
- Time after start of exposure: after 3 and 60 minutes


SCORING SYSTEM:
Exposure sites were evaluated for erythema and edema in accordance with the method of Draize which is the same as in the OECD guideline 404:
Erythema and Eschar Formation:
-no erythema......................................................0
- very slight erythema (barely perceptible,
edges of area not well defined)....1
- well defined reythema......................................2
- moderate to severe erythema........................3
- severe erythema, crimson red, with slight
eschar formation (injuries in depth)...............4

Edema Formation:
-no edema.........................................................0
- very slight edema (barely perceptible,
edges of area not well defined).......1
- slight oedema (edges of area well defined
by definite raising)...........................................2
- moderate edema (area raised
approximatively 1 mm)..................................3
- severe edema (raised more than 1 mm
and extending beyond area of application)....4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: #1, 2, 3, 4, 7, 8
Time point:
24/48 h
Score:
3.66
Max. score:
4
Reversibility:
not fully reversible within: 48h
Remarks on result:
other: Score obtained after 3 minute exposure
Irritation parameter:
edema score
Basis:
animal: #1, 2, 3, 4, 7, 8
Time point:
24/48 h
Score:
2.75
Max. score:
4
Reversibility:
not fully reversible within: 48h
Remarks on result:
other: Score obtained after 3 minute exposure
Irritation parameter:
erythema score
Basis:
animal: #1-8
Time point:
24/48 h
Score:
3.87
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: score obtained after 60 minute exposure
Irritation parameter:
edema score
Basis:
animal: #1-8
Time point:
24/48 h
Score:
3.37
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: score obtained after 60 minute exposure
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 mini
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: score after 3 mni
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: score noted after 3 min
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: not determined
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 minutes
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: score noted after 3 minutes
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 min
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 mni
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 min
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 minutes
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 min
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 min
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: score after 3 min
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 min
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 min exposure
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 min exposure
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 min exposure
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 3 min exposure
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 min exposure
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 mni exposure
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 min expsoure
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 mni exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 min exposure
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 min exposure
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 minute exposure
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 min exposure
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 min exposure
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 min exposure
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 min exposure
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
48 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 mni exposure
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 min exposure
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 min exposure
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 mni exposure
Irritation parameter:
edema score
Basis:
animal #4
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: after 60 mni exposure
Irritant / corrosive response data:
There was no evidence of corrosion following the three minute exposure to the test material.
The 60 minute exposure to the test material induced corrosion on two of six sites. As two of the six rabbits had corrosion following the 60 minute exposure and were euthanized immediately after collection of the initial observations for the presense of corrosion was noted.

Any other information on results incl. tables

Table: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test (3 minute exposure)

Score at time point/ Reversibility  Erythema
Max. score: 4
Edema
Max. score: 4
24 h 3/3/4/3/3/3 3/3/3/3/3/3
48 h 3/3/4/3/3/3 3/2/3/2/2/3
Average 24h, 48h 3.66 2.75
Reversibility*) - -

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

Table: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test (60 minute exposure)

Score at time point/ Reversibility  Erythema
Max. score: 4
Edema
Max. score: 4
24 h 4/4/4/3 3/3/4/4
48 h 4/4/4/4 3/3/4/3
Average 24h, 48h 3.87 3.37
Reversibility*) - -

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

Applicant's summary and conclusion

Interpretation of results:
Category I
Remarks:
Migrated information corrosive Criteria used for interpretation of results: other: Regulation EC no.1272/2008 (CLP)
Conclusions:
Under the conditions of this test, n-heptanoic acid is corrosive considering EU classification and is classified Category 1B (corrosive) according to CLP.
Executive summary:

The dermal irritation and corrosivity potentials of n-heptanoic acid were evaluated with New Zealand White rabbits

(WIL, 1994). Single doses (0.5 ml) of n-heptanoic acid ( lot number : 94017 -1) were applied to the shaved, intact skin of eight albino rabbits under occlusive dressings for 3 and 60 minute exposure periods. Application sites were observed immediately after bandage removal and at approximately 24 and 48 hours after dosing for the presence or absence of corrosion or irritation. There were no deaths or significant body weight changes during the study period. There was no evidence of corrosion following the 3 minute exposure to the test material. The score obtained were 3.66 for erythema and 3.37 for edema. Corrosion was present on two of six rabbits at the initial observation following the sixty minute exposure to n-heptanoic acid. The score obtained were 3.87 for erythema and 3.37 for edema.