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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28.11.1983 to 23.01.1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Method: Variation of Magnusson and Kligman method.
GLP compliance:
no
Remarks:
pre-GLP
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
An LLNA study was not performed because there is an existing reliable study for skin sensitisation using the Guinea Pig Maximisation test method.

Test material

Constituent 1
Chemical structure
Reference substance name:
Nitrilotrimethylenetris(phosphonic acid)
EC Number:
229-146-5
EC Name:
Nitrilotrimethylenetris(phosphonic acid)
Cas Number:
6419-19-8
Molecular formula:
C3H12NO9P3
IUPAC Name:
nitrilotrimethylenetris(phosphonic acid)

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: Winkelmann, Borchen

- Weight at study initiation: Average 430 grams for dosed animals, 423 grams for control animals

- Housing: Type 4 Makrolon cages

- Diet: Specialfeed Altromin 3022, ad libitum

- Water: tap water, ad libitum



ENVIRONMENTAL CONDITIONS

- Temperature (°C): ca. 23°C

- Humidity (%): 50-65%

- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light


Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
water
Concentration / amount:
5%
Challenge
Route:
other: epicutaneous (need translation)
Vehicle:
water
Concentration / amount:
5%
No. of animals per dose:
20
Details on study design:
The skin under the shoulder blade was shaved. Only animals with healthy skin were employed. 3 injections were prepared as follows:

A.     TEST ANIMALS
1 - Freund's adjuvant, volume: 0.1 mL
2 – 5% test material, volume: 0.1 mL as an aquatic solution
3 – Mixture of Freund’s adjuvant and test material as a 1:1 ratio, final concentration 5%, volume 0.1 mL

B.     CONTROL ANIMALS
1 – Freund’s adjuvant, volume 0.1 mL
2 – Aqueous solution, volume 0.1 mL
3 – Mixture of adjuvant/aqueous solution 1:1, volume 0.1 mL

A week after the initial administration, the test material was re-administered epicutaneously further down the torso.

Further sensitization was induced with a patch test. The test material was administered 5% in Vaseline. After 48 hours, the dressings were removed. The control animals were treated with Vaseline only.

14 Days after the induction treatment, a 5x5cm area was shaved in both flanks of each animal. 0.1 mL of 5% test substance in aqueous solution was applied onto the right flank and 0.1 mL of aqueous solution alone to the left flank under a patch for 24 hours.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5% test substance in aqueous solution
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5% test substance in aqueous solution
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
aqueous solution
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
aqueous solution
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Group:
positive control
Dose level:
N/a
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
other: positive control was not specified.
Reading:
2nd reading
Group:
positive control
Dose level:
N/a
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
other: positive control was not specified

Any other information on results incl. tables

Test substance group response:

Following the intracutaneous application, one animal died immediately with bleeding from the nose. No evidence of sensitisation was observed.  Necropsy findings included catarrhal enteritis, bulging stomach and cecum (indigestion), pulmonary congestion, enlarged left side of the heart and clear structure of the liver lobules.

CONTROL GROUP RESPONSES

One animal died during the exposure.

No evidence of sensitisation was observed. After removal of the patch, one animal had white dots in the left eye.

During the treatment free period, the Freund’s adjuvant resulted in necrosis and later scar tissue. After the Patch-test of 48 hours, general redness was observed and the injection sites were blood stained. Crust formation was present at injection sites in both the test and control animals.

Further details are available in the study report, however, needs proper translation.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a skin sensitisation study (Reliability 1), conducted according to a protocol similar to OECD Test Guideline 406 and pre-GLP, ATMP-H (without information on active acid content) was not sensitising to the skin of guinea pigs. One animal from the control group and the test group respectively died. The Freund’s adjuvant resulted in necrosis and later scar tissue. No sensitising potential was observed in the guinea pigs.