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Diss Factsheets

Administrative data

Description of key information

No skin sensitisation data are available for ATMP N-oxide 5K. Therefore, the read across data for the analogous substance ATMP-H have been used. 

In a read-across in vivo skin sensitisation study, conducted according to a protocol similar to OECD Test Guideline 406 but not in compliance with GLP, ATMP-H 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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
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 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


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 chemical
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 chemical
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
Hours after challenge:
24
Group:
positive control
Dose level:
Not specified
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
other: positive control was not specified.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Not specified
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
other: Positive control was not specified

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, but needs proper translation.

Interpretation of results:
GHS criteria not met
Conclusions:
In a skin sensitisation study, conducted in a manner similar to OECD 406 but not in compliance with GLP, ATMP 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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In the key read-across skin sensitisation study, conducted according to a protocol similar to OECD Test Guideline 406, but not in compliance with GLP, 3 injections to the skin occurred for of 20 female Pirbright guinea-pigs and another 20 Pirbright guinea-pigs which served as a control group. For the test group, the first injection contained 0.1 mL of Freund’s adjuvant, the second injection contained 0.1 mL of ATMP-H (as an aquatic solution) and the third injection contained 0.1 mL of a mixture of Freund’s adjuvant and ATMP-H as a 1:1 ratio with a final concentration of 5%.

The control animals also received 3 injections, the first injection contained 0.1 mL of Freund’s adjuvant, the second injection contained 0.1 mL of an aqueous solution and the third injection contained 0.1 mL of a mixture of Freund’s adjuvant and the aqueous solution in a 1:1 ratio.

A week after the initial administration, the test material ATMP-H was re-administered epicutaneously further down the torso. Further sensitisation was induced with a patch test. 5% of ATMP-H was administered 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. Application of 0.1 mL of the 5% test substance in aqueous solution occurred to the right flank and 0.1 mL of the aqueous solution only was applied to the left flank under a patch for 24 hours.

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. Moreover, one animal in the control group died. No evidence of sensitisation was observed.  After removal of the patch, one animal had white dots in the left eye (Henkel, 1984).

In a supporting skin sensitisation study, conducted according to a guideline similar to OECD Test Guideline 406, ATMP-H was concluded to not be sensitising to the skin of guinea pigs. Slight positive reactions were obtained from 8 test animals and 6 negative control animals 24 hours after the challenge. Additionally, positive reactions were obtained from 5 test animals and 2 control animals 48 hours after challenge. The body weights of the test and control animals showed a normal and parallel development in the course of the test. The test compound can be graded as non-sensitising for guinea pigs (Henkel, 1982).

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 read-across data, no classification is required for skin sensitisation for ATMP-N-oxide-5K according to Regulation (EC) No. 1272/2008.