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:
key study
Study period:
from 1988-05-11 to 1988-10-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, Magnusson and Kligman method

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): tetramethyldiaminopropane (TMPDA)
- Physical state: liquid
- Analytical purity: 99.62%
- Purity test date: 1988-04-25
- Lot/batch No.: 8804191
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: albinos Dunkin Hartley, centred'élevage Shamrock Bio Service, 78150, Gambais, France
- Age at study initiation:
- Weight at study initiation: 366+/-15g (males) and 335+/-14g (females)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum pellet diet ref. 106 (U.A.R, 91360 Villemoisson-sur-Orge, France)
- Water (e.g. ad libitum): water filtered with 0.22µ (Société Millipore, 78140 Velizy, France)
- Acclimation period: 9days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18+/-3°C
- Humidity (%): 50+/-20%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To: 1988-06-23

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
physiological saline
Challenge
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
No. of animals per dose:
5 males and 5 females for control group
10 males and 10 females for test group
Details on study design:
RANGE FINDING TESTS:
0.1%, 5%, 10%, and 25% concentrations were tested by intradermal route
1%, 10%, 25% and 50% concentrations were tested by cutaneous route

MAIN STUDY
A. INDUCTION EXPOSURE

Intradermal induction D1
3 injections on the scapular area:
. 0.1mL of Freund's complete adjuvant 50% in 0.9% NaCl
. 0.1mL of TMDAP 0.1% in 0.9% NaCl (treated group) or vehicle (control group)
. 0.1mL of a mixture 50/50 (V/V) of Freund complete adjuvant 50% in 0.9% NaCl and vehicle (for control group) or TMDAP 0.1% in 0.9% NaCl (for treated group)

Cutaneous induction D9
. On day 7, the irritation created with the application of sodium Laurylsulfate 10% in vaseline.
. On day 8, occlusive application on the scapular area of 0.5mL of TMDAP 10% (for treated group) or vehicle (for control group) for 48hours.


B. CHALLENGE EXPOSURE D26
On day 22, 24-hour occlusive application on the scapular area of 0.5mL of TMPDA 1% on the right flank and 0.5mL of the vehicle on the left flank.
Reactions are evaluated 24 and 48 hours after removal of the dressing.
Positive control substance(s):
not specified

Study design: in vivo (LLNA)

Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
1%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 20.0.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
According to the maximization method of Magnusson and Kligman, TMPDA did not induce any sensitization process in the guinea-pig.
Executive summary:

The delayed contact hypersensivity of tetramethyldiaminopropane (TMPDA) was evaluated in Guinea pigs according a protocol similar to OECD N°406 guideline (Magnusson and Kligman test). The induction phase has been realized both by intradermal route on day 1 (TMPDA 0.1% in vehicle) and by cutaneous route on day 9 (TMPDA 10%) in 2 groups of guinea pigs: 5 males and 5 females for control group and 10 males and 10 females for treated group. The challenge phase was realized on day 24 by cutaneous application of TMPDA 1%; the cutaneous reactions were scored 24 and 48 hours after the challenge phase. Neither mortality nor clinical signs were observed during the study. 24 and 48hours after removal of the dressing, no reaction was observed.

In conclusion, TMPDA did not induce any sensitization process in the guinea pig under these experimental conditions.