Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to recommended guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
venlafaxin 2nd intermediate (amino-hexanol)
IUPAC Name:
venlafaxin 2nd intermediate (amino-hexanol)
Test material form:
solid: crystalline

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Husbandry:
Number of animal room: 618
Housing: Animals were housed individually in metal cages
Lighting periods: 12 hours daily, from 6.00 am to 6.00 pm
Temperature: 20±3°C
Relative humidity: 50±20%

Food and feeding
Animals received UNIPLUS standard diet for rabbits produced by AGRIBRANDS Europe, Karcag, Kunmadarasi street, Hungary, ad libitum.

Water supply
Animals received tap water as for human consumption ad libitum from automatic self supplying water system.

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated skin of each animal served as a control
Amount / concentration applied:
0.5g of venlafaxin 2nd intermediate
Duration of treatment / exposure:
4 hours
Observation period:
Animals were examined for signs of erythema and edema, and the responses scored at 60 minutes, and then at 24, 48, 72 hours, 1 and 2 weeks after the patch removal.
Number of animals:
3

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 14 days
Score:
ca. 2.16
Max. score:
8
Reversibility:
fully reversible
Irritant / corrosive response data:
In the first hour after the patch removal in two animals (No.: 8090 and 8095) moderate, in one animal (No.: 8076) well defined erythema was observed. In every treated animal very slight edema occurred.
In 24 hours after the patch removal in one animal (No.: 8090) severe erythema was observed. Severe necrosis, black coloured area was found on the treated skin surface. In one animal (No.8095) moderate, in one animal (No.8076) well defined erythema were observed.
In 48 hours after the patch removal in every treated animal very slight erythema was observed. Severe necrosis, black coloured dry and hard area was found in two animals (No.:8090 and 8095) and in one rabbit (No.:8076) the treated skin surface was dry and hard.
In the 72 hours after the patch removal in every treated animal very slight erythema was observed. The treated skin surface was dry and hard, desquamation began.
At the first week after the patch removal the erythema abated in every treated animal. In two cases (No. 8076, 8095) advanced desquamation was observed. In one animal No.: 8090 the treated skin surface was black, dry and hard. In this case starting desquamation was found.
At the second week after the patch removal no erythema or edema were observed on the treated skin surface, the eschar formation peeled and the necrosis recovered. The skin irritation effect of the test item proved to be reversible.

Any other information on results incl. tables

Classification of Test Items

Index of treated skin:            (A+ B)I(NXT)=c

A= total score of erythema

B = total score of edema

N =animal number

T = number of scoring, when the score is not zero

C = irritation index

 

 

0 - 0.5            non irritant

0.6 - 3.0         slightly irritant

3.1- 5.0          moderately irritant

5.1 - 8.0         severely irritant

 

 

 

SCORING OF ERYTHEMA FORMATION

Table 1

 

 

Animal N°/ Sex

1 h

24 h

48 h

72 h

7 d

14d

8090/M

3

4

1

1

0

0

8095/M

3

3

1

1

0

0

8076/M

2

2

1

1

0

0

TOTAL / A

8

9

3

3

0

0 = 23

 

 

 

SCORING OF EDEMA FORMATION

Table 2

 

 

Animal N°/ Sex

1 h

24 h

48 h

72 h

7 d

14d

8090/M

1

0

0

0

0

0

8095/M

1

0

0

0

0

0

8076/M

1

0

0

0

0

0

TOTAL / B

3

0

0

0

0

0 = 3

 

 

INDEX of skin irritation: (A(23)+B(3))I12=C(2.16)

 

M=male

d =day

h =hour

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item Venlafaxin 2nd Intermediate was judged as irritant.
According to Regulation (EC) n. 1272/2008 and Directive 67/548/EEC, the substance should be classified as skin irritant 2 H315 and as Xi R38.