Registration Dossier

Diss Factsheets

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
Study period:
March/April 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Method was not available

Test material

Constituent 1
Chemical structure
Reference substance name:
N-[2-[(2-bromo-4,6-dinitrophenyl)azo]-5-(diethylamino)phenyl]acetamide
EC Number:
258-110-1
EC Name:
N-[2-[(2-bromo-4,6-dinitrophenyl)azo]-5-(diethylamino)phenyl]acetamide
Cas Number:
52697-38-8
Molecular formula:
C18H19BrN6O5
IUPAC Name:
N-{2-[(2-bromo-4,6-dinitrophenyl)diazenyl]-5-(diethylamino)phenyl}acetamide
Test material form:
solid: bulk
Details on test material:
Dispersol Blue H69507

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
albino Dunkin-Hartley guinea pigs
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, U.K.
- Weight at study initiation: 333 - 393g
- Age: seven to eleven weeks
- Housing: groups of up to 4
- Diet: Guinea Pig FD1 Diet, Special Diet Services Limited, Witham, Essex, U.K. ad libitum
- Water: tap water ad libitum
- Acclimatisation period: five days,

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 25°C
- Humidity (%): 45 to 60%
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 16. March To: 26. April 1987

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
arachis oil
Concentration / amount:
1% / 2 x 0.1 mL
1% / 2 x 0.1 mL in arachis oild : Freund's Complete Adjuvant (FCA) 1:1
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
25% (w/w) in petroleum jelly B.P. / 0.2 to 0.3 mL


Day(s)/duration:
on Day 8 for 48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
25% (w/w) in petroleum jelly B.P. / 0.1 to 0.2 mL
Day(s)/duration:
on Day 22 for 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Determination of primary not irritating concentration: 4
Determination of intradermal tolerability: 2
Control group: 10
Treatment group: 20
Positive control substance(s):
yes

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
14
Total no. in group:
20
Clinical observations:
yellow/green coloured staining of skin
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
11
Total no. in group:
20
Clinical observations:
yellow/green coloured staining of skin; one animal not evaluable due to skin alterations was counted as positive
Remarks on result:
positive indication of skin sensitisation
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
25%
No. with + reactions:
4
Total no. in group:
20
Clinical observations:
yellow/green coloured staining of skin; one animal not evaluable due to skin alterations was counted as positive
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow/green coloured staining of skin
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow/green coloured staining of skin
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
yellow/green coloured staining of skin

Any other information on results incl. tables

Yellow/green coloured staining of the skin was noted at the majority of test sample sites but did not prevent assessment of the skin responses.

Positive skin responses (erythema score >1) were noted at fourteen of the test sample sites on the test animals at the 24-hour observation. Slight loss of skin suppleness was also noted at one of these sites at this time.

A positive skin response had developed at one additional test sample site on the test animals at the 48-hour observation. A further observation was therefore made 72-hours after dressing removal but no additional positive

skin responses were noted. Common signs of desquamation and occasional signs of superficial cracking and thickening of the skin were apparent at the test sample sites on the test animals at both the 48 and 72-hour

observations.

No adverse skin reactions were noted at the vehicle control sites on the test animals or test sample or vehicle control sites on the control animals at the 24, 48 or 72-hour observations.

Bodyweight gains of surviving guinea pigs in the test group, between day 0 and day 24, were comparable to those observed in the control group animals over the same period.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The test substance caused positive reactions in 70%, 55% and 20% of animals after 24, 48, and 72 hours after removal of the test substance; it is hence considered to be a skin sensitiser.
Executive summary:

A study was performed to assess the skin sensitisation potential of the test sample in the albino guinea pig. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 406 "skin Sensitisation" - Magnusson and Kligman Maximisation Test.

 

Twenty test and ten control animals were used for the main study.

Following sighting studies, the following concentrations were used in the induction and challenge phases:

Intradermal Induction       1% (w/v) in arachis oil

Topical Induction             25% (w/w) in petroleum jelly

Topical Challenge             25% (w/w) in petroleum jelly

Yellow/green coloured staining of the skin was noted at the majority of test sample sites but did not prevent assessment of the skin responses.

Positive skin responses (erythema score >1) were noted at fourteen of the test sample sites on the test animals at the 24-hour observation. Slight loss of skin suppleness was also noted at one of these sites at this time.

A positive skin response had developed at one additional test sample site on the test animals at the 48-hour observation. A further observation was therefore made 72-hours after dressing removal but no additional positive

skin responses were noted. Common signs of desquamation and occasional signs of superficial cracking and thickening of the skin were apparent at the test sample sites on the test animals at both the 48 and 72-hour

observations.

No adverse skin reactions were noted at the vehicle control sites on the test animals or test sample or vehicle control sites on the control animals at the 24, 48 or 72-hour observations.

Bodyweight gains of surviving guinea pigs in the test group, between day 0 and day 24, were comparable to those observed in the control group animals over the same period.

The test substance caused positive reactions in 70%, 55% and 20% of animals after 24, 48, and 72 hours after removal of the test substance; it is hence considered to be a skin sensitiser.