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Description of key information

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
Study period:
2004-08-24 - 1004-10-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
OECD 406 (1992)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
At the time of study performance the LLNA was not the current standard test method.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
Species/strain: Guinea-pig/Dunkin Hartley, Crl:(HA)BR
Sex: male
Supplier: Charles River Wiga GmbH, D-97320 Sulzfeld
Age: 16 days
Route:
other: intracutaneous induction
Vehicle:
other: 0.5% solution of Tylose MH 1000 in deionised water
Concentration / amount:
Concentration of test material and vehicle used at induction:
Induction: i.c.: 5 % (w/v) suspesion in a 0.5 % (m/v) of Tylose in deionised water

solution of Tylose MH 1000 in

deionised water

Induction: e.c.: 25 % (w/w) mixture of the test item with

vaseline

Concentration of test material and vehicle used for each challenge:
25 % (w/w) mixture of the test item with vaseline
Route:
epicutaneous, occlusive
Vehicle:
other: 0.5% solution of Tylose MH 1000 in deionised water
Concentration / amount:
Concentration of test material and vehicle used at induction:
Induction: i.c.: 5 % (w/v) suspesion in a 0.5 % (m/v) of Tylose in deionised water

solution of Tylose MH 1000 in

deionised water

Induction: e.c.: 25 % (w/w) mixture of the test item with

vaseline

Concentration of test material and vehicle used for each challenge:
25 % (w/w) mixture of the test item with vaseline
No. of animals per dose:
Number of animals in test group: 10
Number of animals in negative control group: 5
Positive control substance(s):
not required
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25 %
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25 %. No with. + reactions: 1.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
25 %
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 25 %. No with. + reactions: 1.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
25 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 25 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
25%
No. with + reactions:
10
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Dose level:
25%
No. with + reactions:
10
Total no. in group:
10

Maximum concentration not causing irritating effects in preliminary test: 25 %

Signs of irritation during induction:
only after i.c. induction: oedema

Evidence of sensitisation of each challenge concentration:
The administration of the 25 % (w/w) mixture of the test
item with vaseline caused only a slight erythema in one of
the ten animals of the dose group on day 23.

Number of animals with skin sensitisation reaction after administration of N(2-Nitrophenyl)phosphoric triamide

(left flank: control; right flank: test item)

Test group

Time after challenge

48hours (Day23)

72hours (Day24)

Left flank

Right flank

Left flank

Right flank

Animals with skin sensitisation reaction/used animals

Control group

0/5

0/5

0/5

0/5

Dose group

0/10

1 / 10

0/10

1 / 10

from this

 

 

 

 

grade 1

 

1/10

 

1 / 10


Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
N-(2-Nitrophenyl)phosphoric triamide is not a skin sensitiser.
Executive summary:

The skin sensitisation potential of the test item N-(2-Nitrophenyl)phosphoric triamide was

investigated in the Guinea-Pig Maximisation Test with the Dunkin Hartley albino strain, whose sensitivity to Benzocaine had been demonstrated, according to OECD guideline 406.

The choice of doses for the main experiment based on the results of the pilot study.

None of the animals died or showed clinical signs during the course of investigation.

The body weights and the body weight gain were not affected by the treatment.

The intracutaneous injection of the 5 % (w/v) suspension of the test item in a 0.5 % Xylose solution induced oedema. In combination with sensitisation potentiating FCA slight to moderate erythema and oedema were observed.

The epicutaneous administration of the 25 % (w/w) mixture of the test item with vaseline did not cause any irritation signs.

The challenge with the 25 % (w/w) mixture of the test item with vaseline caused only a slight erythema in one of the ten animals of the dose group.

The skin fold thickness was not affected by the challenge.

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

A GLP-study was performed to assess the skin sensitisation potential of the test material in the guinea pig. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 406 (Guinea Pig Maximisation Test).

N-(2-Nitrophenyl)phosphoric triamide was found to be a non-sensitiser to guinea pig skin.

For skin sensitisation, there is no reason to believe that results obtained in experimental animals would not be applicable to humans.

No further testing is required. The available data is adequate for risk assessment and classification and labelling purposes.

Migrated from Short description of key information:

Guinea pig maximisation test: negative

Justification for selection of skin sensitisation endpoint:

Only one study available.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No data gaps were identified. The available data are adequate for risk assessment and classification and labelling purposes.

Justification for classification or non-classification

N-(2-Nitrophenyl)phosphoric triamide is not classified as skin sensitiser.