Registration Dossier

Administrative data

Description of key information

- Skin irritation

not irritating (Fed. Reg. 38, No. 187, section 1500.41, p. 27019,  Sept. 27, 1973).

- Eye irritation

not irritating (J.H. Kay et col., in vivo Test de Draize, J.Soc.Cos.Chem. 13/281, 1962).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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: Non-GLP study, deviations to current testing protocols
Qualifier:
according to
Guideline:
other: FED. REG. 38, NO. 187, SECTION 1500.41 P. 27019, SEPT. 27, 1973
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: GAUKLER; D-6050 Offenbach/Main, Germany
- Weight at study initiation: 2,45; 2.46; 2.89; 2.88; 3.21; 2.98 (kg)
- Housing: cage made of stainless steel with wire mesh walk floors, floor area: 40 cm X 51 cm, No. of animals per cage: 1; No bedding in the cages; Sawdust in the waste trays
- Diet (e.g. ad libitum): about 130 g per animal per day
- Water (e.g. ad libitum): about 250 mL tap water per animal per day
- Acclimation period: at least 8 days before the beginning of the study: same housing conditions as during the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 h/12 h (6.00 - 18.00 h/18.00 - 6.00 h)

IN-LIFE DATES: From: 28.01.1985 To: 12.02.1985
Type of coverage:
occlusive
Preparation of test site:
other: clipping of fur
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL of test substance on a 2.5 cm X 2.5 cm patch
Duration of treatment / exposure:
24 hour(s)
Observation period:
30 - 60 min, 24 h, 48 h, 72 h, 8 d, 15 d
Number of animals:
6 (5 males, 1 female)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm X 2.5 cm

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM:
EVALUATION OF ERYTHEMA AND EDEMA:
0 = NONE
1 = YERY SLIGHT
2 = WELL-DEFINED
3 = MODERATE TO SEVERE
4 = SEVERE
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Scaling observed in 1/6 animals, fully reversible within 15 days
Readings Animal Erythema Edema Further findings
24 h 1 2 1  
  2 2 0  
  3 2 1  
  4 2 1 R:E
  5 2 0  
  6 2 1  
48 h 1 1 0  
  2 1 0  
  3 2 0  
  4 2 0 R:E
  5 1 0  
  6 2 0  
72 h 1 1 0  
  2 1 0  
  3 2 0  
  4 2 0 R:E
  5 1 0  
  6 2 0  
8 d 1 0 0  
  2 0 0  
  3 0 0  
  4 1 0 S
  5 1 0  
  6 0 0  
15 d 1 0 0  
  2 0 0  
  3 0 0  
  4 0 0  
  5 0 0  
  6 0 0  
Mean (24 h - 72 h) 1 1.3 0.3  
  2 1.3 0.0  
  3 2.0 0.3  
  4 2.0 0.3  
  5 1.3 0.0  
  6 2.0 0.3  
Mean (24 h - 72 h) all animals 1.7 0.2  

R:E = Erythema, extending beyond the area of exposure S = Scaling. Similar findings after application on abraded skin with mean (24 h - 72 h) erythema/edema score (all animals): 1.7/0.3 (not relevant for assessment). Findings 30 - 60 min after patch removal were not reported.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
april 1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test was not conducted according to an OECD Test Guideline. Acceptable data.
Qualifier:
no guideline followed
Principles of method if other than guideline:
according to ref.: J.H. Kay et col., J.Soc.Cos.Chem. 13/281, 1962
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration: undiluted
Duration of treatment / exposure:
Group I - 168 hours (not rinsed)
Group II - 2 seconds (rinsed)
Group III - 4 seconds (rinsed)
Observation period (in vivo):
168 hours (at 1, 24, 48, 72, 96 and 168 hours)
Number of animals or in vitro replicates:
Group I - 3
Group II - 3
Group III - 3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Group I: not rinsed; Group II: rinsed with water after 2 sec.; Group III: rinsed with water after 4 sec.
- Time after start of exposure: 2 sec. and 4 sec.

SCORING SYSTEM: according to ref.: J.H. Kay et col., J.Soc.Cos.Chem. 13/281, 1962
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 hour
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: overall score from all groups
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: overall score from all groups
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 1 hour
Score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: not rinsed
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 1 hour
Score:
2
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: not rinsed
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 1 hour
Score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: not rinsed
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: 1 hour
Score:
2
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: rinsed after 2 sec.
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: 1 hour
Score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: rinsed after 2 sec.
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
other: 1 hour
Score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: rinsed after 2 sec.
Irritation parameter:
conjunctivae score
Basis:
animal: #7
Time point:
other: 1 hour
Score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: rinsed after 4 sec.
Irritation parameter:
conjunctivae score
Basis:
animal: #8
Time point:
other: 1 hour
Score:
2
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: rinsed after 4 sec.
Irritation parameter:
conjunctivae score
Basis:
animal: #9
Time point:
other: 1 hour
Score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: rinsed after 4 sec.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: overall score from all groups
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: Overall score from all groups
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Remarks on result:
other: overall score from all groups
Irritant / corrosive response data:
A slight irritation of the conjunctivae was observed during the few hours after application of pure 2-Ethylhexyl 4-methoxycinnamate. This irritation is manifested by the presence of some more capillaries injected into the eye treated than on the eye not treated. No effect could be detected 24 hours after application of the test substance. No effect of rinsing was observed.
No effects on cornea and iris were observed.

ObservationTime

Animal nr.

Group I

Conjunctivae

Group II

Conjunctivae

Group III

Conjunctivae

Results

1 hour

1

A2

A1

A2

3.3

1 hour

2

A1

A2

A1

 

1 hour

3

A2

A2

A2

 

24 hours

1

 

 

 

0

24 hours

2

 

 

 

24 hours

3

 

 

 

Interpretation of results:
GHS criteria not met
Conclusions:
No effects on eye irritation could be detected 24 hours after application of 2-Ethylhexyl 4-methoxycinnamate. Based on these results, 2-Ethylhexyl 4-methoxycinnamate does not need to be classified as irritating according to the criteria outlined in regulation 1272/2008/EC.
Executive summary:

2-Ethylhexyl 4-methoxycinnamate had been injected into the left eye of 3 albino rabbits without rinsing, the left eye of another 3 albino rabbits were rinsed after 2 and 4 seconds, resp. Cornea, iris, and conjunctivae were examined. A slight irritation of the conjunctivae was observed during the few hours after application of pure 2-Ethylhexyl 4-methoxycinnamate. This irritation is manifested by the presence of some more capillaries injected into the eye treated than on the eye not treated. No effect, however small, could be detected 24 hours after application of the test substance. Based on these results, 2-Ethylhexyl 4-methoxycinnamate does not need to be classified as irritating according to the criteria outlined in regulation 1272/2008/EC.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion potential of Ethylhexyl Methoxycinnamate was studied in white rabbits according to Fed. Reg. 38, No. 187, section 1500.41, p. 27019, Sept. 27, 1973 (BASF AG, 1985). Taking into consideration the stringent application conditions in the key study, i.e. 24 hours occlusive, only slight irritative potential of the test compound has been found. The findings do not fulfil the criteria as skin irritant according to regulation 1272/2008/EC (CLP/EU-GHS).

The primary eye irritation potential of Ethylhexyl Methoxycinnamate was studied according to the in vivo Test de Draize (ref.: J.H. Kay et col., J.Soc.Cos.Chem. 13/281, 1962) in albino rabbits (Dufour, 1971). The results of this study do not fulfil the criteria as eye irritant according to regulation 1272/2008/EC (CLP/EU-GHS).

Justification for classification or non-classification

Both the key study and supporting studies indicate that Ethylhexyl Methoxycinnamate does not induce significant or irreversible damage to the rabbit skin and eye. Therefore, it can be concluded that the substance is not irritating and therefore does not need to be classified as such according to the criteria outlined in 1272/2008/EC (CLP/EU-GHS).