Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
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:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Freund's complete adjuvant test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
Husbandry
Animal health: Only animals in acceptable health condition were used for the test. It is certified by the veterinarian
Cage type: Animals were housed in macrolon cages, size III, with 3 or 2 animals/cage ( 42 x 42 x 19 cm)
Bedding: laboratory bedding
Animal room: 614
Light: 12 hours daily from 6 a.m. to 6 p.m. (artificial light)
Temperature: 20 ±3°C
Relative humidity: 30-70%
Rate of air exchange: 13-17 hours

Food and Feeding
Animals received UNIPLUS standard diet for rabbits produced by AGRIBRANDS Europe Hungary, ad libitum.

Water Supply
The animals received tap water, as for human consumption, ad libitum containing 50 mg/100mL Ascorbic acid.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Remarks:
NaCl 0.9%
Concentration / amount:
Series of test item concentrations were tested to specify the primary irritation by intradermal injection and dermal application. Four dose levels were tested in the preliminary dose range finding study to specify the primary irritation by intradermal injection and four dose levels by dermal application.
The test item was applied in concentrations of 0.1, 1, 5, 10, 25, 50 and 75% (w/v).
For the intradermal application 0.1 mL formulated test item was injected in concentrations of 0.1, 1, 5 and 10% (w/v). Two different concentrations were applied
per animal to the hairless skin on the right and left flanks, and two animals were employed per concentration tested.
For the dermal application 0.5 mL formulated test item was applied onto the skin of the animals in concentrations of 10, 25, 50, 75% (w/v). A closed patch exposure was employed by means of an occlusive bandage. Two animals/ two different concentrations were used.
It was found that 0.5 mL of test formulation in concentrations of 10, 25 and 50% produced no reaction on the skin of guinea pigs. In concentration of 75% very slight and well defined erythema occurred one hour after the patch removal.
Challengeopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Remarks:
NaCl 0.9%
Concentration / amount:
Series of test item concentrations were tested to specify the primary irritation by intradermal injection and dermal application. Four dose levels were tested in the preliminary dose range finding study to specify the primary irritation by intradermal injection and four dose levels by dermal application.
The test item was applied in concentrations of 0.1, 1, 5, 10, 25, 50 and 75% (w/v).
For the intradermal application 0.1 mL formulated test item was injected in concentrations of 0.1, 1, 5 and 10% (w/v). Two different concentrations were applied
per animal to the hairless skin on the right and left flanks, and two animals were employed per concentration tested.
For the dermal application 0.5 mL formulated test item was applied onto the skin of the animals in concentrations of 10, 25, 50, 75% (w/v). A closed patch exposure was employed by means of an occlusive bandage. Two animals/ two different concentrations were used.
It was found that 0.5 mL of test formulation in concentrations of 10, 25 and 50% produced no reaction on the skin of guinea pigs. In concentration of 75% very slight and well defined erythema occurred one hour after the patch removal.
No. of animals per dose:
Test group: 10 animals
Control group: 5 animals
Challenge controls:
24 hours before the challenge treatment the left and the right flank areas (5x5 cm) of each animal were prepared for application. The challenge was performed as a dermal exposure (Closed Patch Test).
Left shaved flank areas of the animals (both the test and the control) were treated with 0.50 ml of the test item (in concentration 50%). The right shaved flank areas were treated with 0.50 ml of distilled water, in all cases. Time of exposure was 24 hours.
Positive control substance(s):
yes

Results and discussion

Positive control results:
5 control animals were exposed to vehicle during induction treatment and they were treated with the reference item on the challenge day only. No visible changes were found at the 241 h and 481 h hour examinations. During the challenge exposure, the reference item POTASSIUM DICHROMATE (in concentration of 0.3%) did not evoke primary irritation.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 5.0.

Any other information on results incl. tables

Dermal symptoms of guinea pigs challenged with test item venlafaxin2ndintermediate

  Table 2 

TEST ANIMALS

 

Animal number

SKIN REACTION

24 hours

 

48 hours

 

after the patch removal

left side

right side

left side

right side

112

n.v.c

n.v.c

n.v.c

n.v.c

128

n.v.c

n.v.c

n.v.c

n.v.c

132

n.v.c

n.v.c

n.v.c

n.v.c

147

n.v.c

n.v.c

n.v.c

n.v.c

151

n.v.c

n.v.c

n.v.c

n.v.c

106

n.v.c

n.v.c

n.v.c

n.v.c

107

n.v.c

n.v.c

n.v.c

n.v.c

129

n.v.c

n.v.c

n.v.c

n.v.c

130

n.v.c

n.v.c

n.v.c

n.v.c

131

n.v.c

n.v.c

n.v.c

n.v.c

 

Abbreviations: n.v.c. = no visible change


Dermal symptoms of guinea pigs challenged with test item venlafaxin
2ndintermediate

  Table 3 

CONTROL ANIMALS

 

Animal number

SKIN REACTION

24 hours

48 hours

after the patch removal

 

left side

right side

left side

right side

133

n.v.c

n.v.c

n.v.c

n.v.c

135

n.v.c

n.v.c

n.v.c

n.v.c

136

n.v.c

n.v.c

n.v.c

n.v.c

137

n.v.c

n.v.c

n.v.c

n.v.c

138

n.v.c

n.v.c

n.v.c

n.v.c

 

Abbreviations:          n.V.C. = no visible change


Dermal response scores+ for guinea pigs challenged with test item venlafaxin
2"dintermediate

(Challenge concentration: in concentration Table 4

 

TEST ANIMALS                                                       CONTROL ANIMALS

 

Animal number

Score of dermal reaction

Animal number

Score of dermal reaction

 

24 hours

48 hours

 

24 hours

48 hours

 

after the patch removal

 

after the patch removal

112

0

0

133

0

0

128

0

0

135

0

0

132

0

0

136

0

0

147

0

0

137

0

0

151

0

0

138

0

0

106

0

0

-

-

-

107

0

0

-

-

-

129

0

0

-

-

-

130

0

0

-

-

-

131

0

0

-

-

-

mean of scores

0.00

0.00

mean of scores

0.00

0.00

number of positive/number of tested

0/10

0/10

number of positive/number of tested

0/5

0/5

 

 

 

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item Venlafaxin 2nd Intermediate is considered not sensitising.
According to Directive 67/548/EEC and to Regulation (EC) n. 1272/2008, the substance should not be classified for skin sensitisation.