Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Referenceopen allclose all

Reference Type:
other: authoritative database
Title:
Hazardous Substances Data Bank (HSDB) for Benzotriazole
Author:
U.S National Library of Medicine
Year:
2013
Bibliographic source:
Hazardous Substances Data Bank (HSDB), U.S National Library of Medicine 2013
Reference Type:
secondary source
Title:
Report on skin sensitization (contact allergenic) effect on guinea pigs of TK11’237 with cover letter dated 072893
Author:
NTRL
Year:
1993
Bibliographic source:
NTRL OTS0538207 dated 072893 1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
To assess skin sensitization potential of Benzotriazole on Pirbright white guinea Pig’s skin.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
IUPAC :Benzotriazole
CAS :95-14-7
EC No: 202-394-1
InChI:1S/C6H5N3/c1-2-4-6-5(3-1)7-9-8-6/h1-4H,(H,7,8,9)
Smiles:c12c(nn[nH]1)cccc2
substance type: organic
physical state:solid
Specific details on test material used for the study:
IUPAC :Benzotriazole
CAS :95-14-7
EC No: 202-394-1
InChI:1S/C6H5N3/c1-2-4-6-5(3-1)7-9-8-6/h1-4H,(H,7,8,9)
Smiles:c12c(nn[nH]1)cccc2
substance type: organic
physical state:solid
Molecular weight:119.1265 g/mol
Molecular formula:C6H5N3

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: same Breeded in the laboratory premises.
- Age at study initiation: approx 10 weeks old
- Weight at study initiation: 276-416 gms
- Housing: individually in Macrolon cages type 3.
- Diet (e.g. ad libitum): guinea pig pallets NAFAG No.830, Gossau SG ad libitum supplemented with fresh carrots.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±1°C
- Humidity (%): 50±10%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 14 hrs light cycle

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
Concentration-0.1%
Amount-0.1 ml
Day(s)/duration:
3 weeks
Adequacy of induction:
not specified
Challengeopen allclose all
No.:
#1
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1 ml in 0.1% saline
Day(s)/duration:
1 day
Adequacy of challenge:
not specified
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline
Concentration / amount:
30% in vaseline
Day(s)/duration:
1 day
Adequacy of challenge:
not specified
No. of animals per dose:
Test groups: 20
- Control group: 20
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: No data
- Test groups: 20
- Control group: 20
- Site: flank and back
- Frequency of applications: consecutive days
- Duration: 3 weeks
- Concentrations: 0.1 ml / 0.1%

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 1 days
- Exposure period: 24 hrs
- Test groups: 20
- Control group:20
- Site: flank
- Concentrations: 0.1 ml / 0.1 %
- Evaluation (hr after challenge): 24 hrs

C. RECHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 24 hrs
- Test groups: 20
- Control group: 20
- Site: No data
- Concentrations: 30% in vesline
- Evaluation (hr after challenge): 24 hrs
OTHER: epicuteneous application under occlusion.
Challenge controls:
Not specified
Positive control substance(s):
yes
Remarks:
physiological saline

Study design: in vivo (LLNA)

Statistics:
Fisher's test,( p>0.01)

Results and discussion

Positive control results:
2 out of 20 guine pigs were showing reaction to control.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.1 ml in 0.1% saline
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Hours after challenge:
24
Group:
test group
Dose level:
30% in vaseline
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no skin reaction observed
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
other: Not sensitizing
Conclusions:
Benzotriazole was considered to be non sensitizing after introducing it inta dermally as induction dose 0.1 ml 0.1% and challenge dose after 14 days of resting period , second challenge was introduced as epicuteneous application 30% in vaseline under occlusion no positive reaction was noted.
Executive summary:

  Benzotriazole was evaluated for dermal sensitization in the optimization test. Pirbright white guinea pigs (10/sex/group) were administered 10 consecutive 0.1 ml intracutaneous injections of 0.1% in physiological saline or the vehicle alone. Induction was initiated with an intracutaneous injection both into the shaved flank and into the back, followed by a single injection into the back every other day, Complete Bacto Adjuvant supplemented the 0.1% solution  (1:1, vehicle/adjuvant) in second and third weeks of the induction period. After a 14-day resting period, challenge with 0.1 ml intracutaneous injections of 0.1% in saline into the flanks of control and inducted guinea pigs was given. Injection sites were each inspected 24 hours after induction and challenge. No significant increase in number of positive reactions was noted among inducted guinea pigs. (3/20 positive reactions) relative to controls (2/20 positive reactions). A second challenge, consisting of a subirritant epicutaneous application (30% in vaseline) under occlusive wrap for 24 hours, followed the first by 10 days. Reactions (based on the Draize irritation index) to epicutaneous challenge, evaluated 24 hours later, also failed to demonstrate sensitization in inducted animals (0/20 positive reactions)

No positive reactions were noted.