Registration Dossier

Administrative data

Description of key information

Based on the results the substance was considered as non-irritating to skin but corrosive to the eye (CLP).

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 1995-11-21 to 1995-12-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
92/67/EEC
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Y 01242250
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Animals:

- Source: Chemical pharmaceutical factory Dr. K. Thomae, 88400 Biberach
- Age at study initiation: 3-5 mounths
- Weight at study initiation: 3.4-3.7 kg
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week under study conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/3 3 °C
- Humidity: 50-/- 20%
- Photoperiod: 12 hrs dark / 12 hrs light per day

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
physiological saline
Remarks:
(0.3 mL per animal)
Controls:
no
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
7 days
Number of animals:
3
Details on study design:
TEST SITE

- Area of exposure: 2.5 X 2.5 cm
- Type of wrap if used: cellulose patch on a piece of surgical plaster

REMOVAL OF TEST SUBSTANCE
- Washing : warm tap water
- Time after start of exposure: immedialely after the 4-hour exposure period

SCORING SYSTEM: Draize

Reading:
30-60 min as well as 24,48 and 72 hours after removal of the patches. Because of the persistent irritations in two animals 72 hours after removal of the patches, additional readings were performed after 7 days.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
30-60 min up to 3 days after removal of the plasters two animals showed very slight to well defined erythema and very slight oedema. The third animal exhibited neither erythma nor edema. 7 days after removal of the patches all signs of irritation were reversible.
Interpretation of results:
GHS criteria not met
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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to read-across justification document attached in IUCLID Section 13.
Reason / purpose:
read-across source
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.66
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Crotonic acid was tested in a primary skin irritation/corrosion study in the rabbit according to OECD guideline no. 404 and GLP (Hoechst AG, 1995). Three rabbits were exposed to 0.5 g of the test item dissolved in 0.5 mL isotonic saline, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations for erythema and edema were made 1, 24, 48 and 72 hours and 7 days after exposure and mean values for 24,48 and 72 hours were deduced according to the score of Draize. 30 -60 min up to 3 days after removal of the plasters two animals showed very slight to well defined erythema (score 2) and very slight oedema (score 1 and 0.7). The third animal exhibited neither erythema nor edema (score 0). 7 days after removal of the patches all signs of irritation were reversible. The study is reliable without restrictions.

In a skin irritation study (Hoechst AG (c), 1967) 5 rabbits were exposed to Crotonic acid by epicutaneous treatment once a day for five consecutive days. The test item concentrations were 1% and 10% in sesame oil. Animals treated with the highest test concentration showed redness, chapped and necrotic skin at the exposure area. 1% Crotonic acid induced minimal chapped skin at the exposure area by the end of the five day treatment period. 

In an acute dermal toxicity study (Toxi-Coop Zrt.(b), 2012) 5 male and 5 female rats were exposed to 2000 mg/kg bw Crotonic acid by dermal route and left in contact with the skin for 24 hours. The observation period was 14 -days. The test item caused dermal irritation symptoms that were fully reversible within the 14 -day observation period. As no necrosis was observed and the irritation symptoms were fully reversibel Crotonic acid was considered to be slighly irritating but not corrosive after a 24h exposure period.

Eye irritation

The eye irritation properties of Crotonic acid anhydride was examined in an OECD 405 and GLP compliant study (Hoechst AG, 1997). The study can be used for read across to Crotonic acid because the tested anhydride hydrolyses to Crotonic acid in the moist environment of the eye.

A New Zealand White rabbit was administered with 0.1 mL of the test item, applied to one eye of the rabbit while the other eye, remaining untreated, served as a control. The eyes were examined 1, 24, 48, 72 hours after administration of the test substance. Since effects were still present in the eye after 72 hours, further examinations were carried out after 7 and 14 days. One hour up to 14 days after administration the conjunctiva of the animal showed definitely injected blood vessels up to a diffuse beefy red color and an obvious swelling to a swelling with lids half closed to completely closed. 24 hours up to 14 days after administration the iris showed no reaction to light. Diffuse to opalescent areas of the cornea were observed one hour up to 14 days administration. Additionally, clear-colourless and white-yellow viscous discharge, exfoliation of the conjunctiva and nictating membrane as well as blanched nictitating membrane with hemorrhages were noted during the observation period. 14 days after administration the animal showed extreme vascularization. The study is reliable without restrictions.

In an eye irritation study (Hoechst AG (d), 1967) Crotonic acid (1% and 10% in sesame oil) was installed in the conjunctival sac of the eye of five rabbits and the animals were observed for 1, 3, 7 and 24 hours. Animals treated with the 10% solution showed slight redness, slight to district swelling of the conjunctiva and slight cornea opacity. 1% Crotonic acid induced no eye irritating effects. The reliability of the study is not assignable since only a short summary is available.

 


Justification for selection of skin irritation / corrosion endpoint:
Most reliable study

Justification for selection of eye irritation endpoint:
Most reliable study

Effects on eye irritation: corrosive

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin and eye irritation, the test item is classified and labelled as eye corrosive (H318: "Causes serious eye damage") according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.

Classification regarding skin irritation is not warranted, according to Regulation (EC) No 1272/2008.