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Description of key information

In a reliability 2 study, skin sensitisation study conducted according to a variation of Magnusson and Kligman method, ATMP was not sensitising to the skin of guinea pigs (Henkel, 1984).

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:
28.11.1983 to 23.01.1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Method: other: variation of Magnusson and Kligman method
GLP compliance:
no
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.
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 430g for dosed animals, 423g 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

- Humidity (%): 50-65

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


Route:
intradermal
Vehicle:
water
Concentration / amount:
5%
Route:
other: epicutaneous (need translation)
Vehicle:
water
Concentration / amount:
5%
No. of animals per dose:
20
Details on study design:
50% concentration
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
50%
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 group
Dose level:
50%
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
Remarks on result:
other: positive control was not specified.

TEST SUBSTANCE GROUP RESPONSES

One animal died immediately after the intracutaneous application, 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. Clear structure of the liver lobules.



CONTROL GROUP RESPONSES

One animal died during the exposure.

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

OTHER: The Freund’s adjuvant resulted in necrosis which resulted in scar tissue during the treatment free period of the experiment. After the Patch-test with of 48 hours general redness was seen and the injection sites were blood stained. Crust formation was present at injection sites in both the test and control animals.

Interpretation of results:
GHS criteria not met
Conclusions:
In a skin sensitisation study conducted using a protocol which was a variation of the Magnusson and Kligman method (reliability score 2), ATMP was not sensitising to the skin of guinea-pigs.
Executive summary:

In a skin sensitisation study conducted using a protocol which was a variation of the Magnusson and Kligman method (reliability score 2), ATMP (in water) was applied to the skin of 20 Pirbright guinea-pigs, 20 additional guinea-pigs served as negative controls. One animal from the test and control group died, and the study was negative for skin sensitisation (48 and 72 hours after exposure). Further details are available in the study report, but this needs proper translation.

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

The key study selected for ATMP skin sensitisation was the most reliable and recent study available.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There are no data for respiratory sensitisation.

Justification for classification or non-classification

Based on the available data, no classification is required for skin sensitisation for ATMP-H according to Regulation (EC) No 1272/2008.