Registration Dossier

Administrative data

Description of key information

One study was available (OCDE Guideline 406, and GLP) on guinea pigs (DeJouffrey 1995). No cutaneous reactions attributable to the sensitization potential of DPG, at the maximal technically utilizable concentration of 25% were observed in guinea-pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
This old study on guinea pigs (1995) was available at the time of the Reach registration of this substance.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre d'Elevage Lebeau, 78950 Gambais, France
- Age at study initiation: no data
- Weight at study initiation: 356 +/-22g
- Housing: individually
- Diet (e.g. ad libitum): ad libitum (guinea-pigs sustenance reference 106 diet)
- Water (e.g. ad libitum): filtered tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/-2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): about 12 cycles/hour filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12h/12h
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
INTRADERMAL ROUTE (induction): concentration of 1% (w/w) in the vehicle.
CUTANEOUS ROUTE (induction and challenge): concentration of the test substance i.e. 25% (w/w) in the vehicle.
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
INTRADERMAL ROUTE (induction): concentration of 1% (w/w) in the vehicle.
CUTANEOUS ROUTE (induction and challenge): concentration of the test substance i.e. 25% (w/w) in the vehicle.
No. of animals per dose:
a control group = 5 females ; a treated group = 10 females
Details on study design:
On the day of each treatment, the test substance was ground using a motor and pestle then was prepared in the vehicle.

INTRADERMAL ROUTE :
On day 1, six intradermal injections were made into a clipped area (4 cm x 2 cm) in the scapular region, using a needle mounted on a 1 ml glass syringe. three injections of 0.1 ml were injected into each side of the animal as follow :
Control group : 1 = adjuvant ; 2 = vehicle; 3= adjuvant + vehicle.
Treated group : 1 = adjuvant ; 2 = vehicle et DPG ; 3= adjuvant + vehicle + DPG

CUTANEOUS ROUTE :
On day 7, the scapular area was clipped. As the test substance diluted is shown to be non-irritant after occlusive cutaneous treatment during preliminary test, the animals were treated with 0.5 ml of sodium laurylsulphate (10%) in vaseline to provoke local irritation. On day 8, a cutaneous application on the 6 injection areas (4 cm x 2 cm) of the scapular region was performed.
Control group : application of 0.5 ml of the vehicle
Treated group : application of 0.5 ml of a non-irritant concentration of the test substance i.e. 25% (w/w) in the vehicle.

CHALLENGE PHASE
At the end of the rest period on day 22, the test substance was applied at the Maximum Non-Irritant Concentration (MNIC), i.e. at a concentration of 25% (w/w) in the vehicle. On day 22, the animals from both groups received an application of 0.5 ml of the M.N.I.C. of the test substance on the posterior right flank, and 0.5 ml of the vehicle on the posterior left flank.
Challenge controls:
none
Positive control substance(s):
yes
Remarks:
DNCB
Positive control results:
The guinea pigs which used in recent studies showed a satisfactory sensitization response in 100% animals using a positive sensitizer.
Reading:
other: 1st and 2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
0.5 ml of a 25% solution
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading:
Reading:
other: 1st and 2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.5 ml of a 25% solution
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading:
Reading:
other: 1st and 2nd reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5 ml of a 25% solution
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading:
Reading:
other: 1st and 2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5 ml of a 25% solution
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading:
Reading:
other: 1st and 2nd reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.5 ml of a 0.5% solution
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
other: Reading:
Reading:
other: 1st and 2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.5 ml of a 0.5% solution
No. with + reactions:
5
Total no. in group:
5
Remarks on result:
other: Reading:
Interpretation of results:
GHS criteria not met
Conclusions:
According to the maximization method established by Magnusson and Kligman, no cutaneous reactions attributable to the sensitization potential of 1,3-DIPHENYLGUANIDINE (DPG), at the maximal technically utilizable concentration of 25% (w/) were observed in guinea-pigs.
Executive summary:

The potential of the 1,3-DIPHENYLGUANIDINE (DPG), to induce delayed contact hypersensitivity following intradermal injection and cutaneous application was evaluated in guinea-pigs according to the maximization method of Magnusson and Kligman. The study was conducted in compliance with the Principles of Good Laboratory Practice Regulations.

Fifteen guinea-pigs were allocated to two groups : a control group of 5 females, and a treated group of 10 females. The sensitization potential of DPG was evaluated after a 10 -day induction period during which time the animals were treated with paraffin oil (control group) or DPG (treated group). On day 1, in presence of frenud's complete adjuvant, 0.1 ml of the tst substance at a concentration of 1% (w/w) in the vehicle was administered by intraadermal route. On day 8, 0.5 ml of DPG at a concentration of 25% (w/w) in the vehicle was appplied by cutaneous route during 48 hours by means of an occlusive dressing. After a period of 12 days without treatment, a challenge cutaneous application of 0.5 ml of the vehicle (left flank) and 0.5 ml of DPG at a concentration of 25% (w/w) in the vehicle (right flank) were administered to all animals.

DPG and the vehicle were prepared on a dry gauze pad then were applied to the skin and held in place for 24 hours by means of an occlusive dressing. Cutaneous reactions on the challenge application sites were then evaluated 24 and 48 hours after removal of the dressing. After the final scoring period, the animals were killed. Due to the absence of cutaneous reactions, no skin samples were taken from the challenge application sites from all the animals.

No clinical signs and no deaths were noted during this study. After 24 and 48 hours following removal of the dressing of the cutaneous challenge application of the test substance, no cutaneous reactions were recorded. The guinea-pigs showed a satisfactory sensitization response in 100% animals using a positive sensitizer.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The potential of the DPG, to induce delayed contact hypersensitivity following intradermal injection and cutaneous application was evaluated in guinea-pigs according to the maximization method of Magnusson and Kligman. The study was conducted in compliance with the Principles of Good Laboratory Practice Regulations.

Fifteen guinea-pigs were allocated to two groups : a control group of 5 females, and a treated group of 10 females. The sensitization potential of DPG was evaluated after a 10 -day induction period during which time the animals were treated with paraffin oil (control group) or DPG (treated group). On day 1, in presence of frenud's complete adjuvant, 0.1 ml of the test substance at a concentration of 1% (w/w) in the vehicle was administered by intra-dermal route. On day 8, 0.5 ml of DPG at a concentration of 25% (w/w) in the vehicle was applied by cutaneous route during 48 hours by means of an occlusive dressing. After a period of 12 days without treatment, a challenge cutaneous application of 0.5 ml of the vehicle (left flank) and 0.5 ml of DPG at a concentration of 25% (w/w) in the vehicle (right flank) were administered to all animals.

DPG and the vehicle were prepared on a dry gauze pad then were applied to the skin and held in place for 24 hours by means of an occlusive dressing. Cutaneous reactions on the challenge application sites were then evaluated 24 and 48 hours after removal of the dressing. After the final scoring period, the animals were killed. Due to the absence of cutaneous reactions, no skin samples were taken from the challenge application sites from all the animals.

No clinical signs and no deaths were noted during this study. After 24 and 48 hours following removal of the dressing of the cutaneous challenge application of the test substance, no cutaneous reactions were recorded. The guinea-pigs showed a satisfactory sensitization response in 100% animals using a positive sensitizer.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Mandatory classification :

- Regulation (EC) No 1272/2008 Annex VI Table 3.1: None

 

Self-classification

- Regulation (EC) No 1272/2008 : None