Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion:One study is recorded for this endpoint (Kiplinger, 1994). This study has been identified as suitable to be chosen as key study. Indeed, this study was performed with New Zealand White rabbits following a method comparable to OECD TG 404 with acceptable restrictions. Results showed that n-heptanoic acid is corrosive after a 60-minute occlusive application on the intact rabbit skin in two rabbits and induced severe irritation in other animals.

Eye irritation:No study is recorded for this endpoint. Due to corrosive results in skin irritation/corrosion test, no eye irritation test is required.

Respiratory irritation :Signs of irritation were noted during the exposure and for several days after the exposure before the animals recovered (6 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
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.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
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
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
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.

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

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification

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

-Skin irritation/ corrosion: heptanoic acid is classified corrosive (category 1B), corrosion was observed after 60-minute exposure in 2 animals.

-Eye irritation/ corrosion: heptanoic acid is classified corrosive (category 1), skin corrosive substance shall be considered as leading to serious damage to the eyes as well.

-Respiratory irritation: heptanic acid is classified as irritant for the respiratory tractus (STOT-SE 3 / H335).