Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 607-997-7 | CAS number: 26776-30-7
Endpoint summary
Administrative data
Description of key information
2H-Azepin-2-one, hexahydro-, polymer with 1,6 diisocyanatohexane is not sensitizing in animal studies (Bayer AG, 2003 and Bayer AG, 2007).
Assessment of the test substance concerning respiratory sensitisation is not possible because no data are available for this toxicological endpoint.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2007-06-11 to 2007-06-28
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- 29th Adaption of Guideline 67/548/EEC, B.42
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Principles of method if other than guideline:
- Modified LLNA (IMDS; Integrated Model for the Differentiation of Skin Reactions). Modification refer to the measurement of cell proliferation by cell
counting instead of radioactive labeling. In addition, the acute inflammatory skin reaction is determined to discriminate specific from non-specific activation of immune competent cells in the draining lymph nodes. - GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, Borchen, Germany
- Strain: Hsd Win: NMRI
- Age at study initiation: 9 weeks
- Weight at study initiation: 26 - 32 g
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): 40 - 70
- Air changes (per hr): about 10
- Photoperiod (hrs dark/ hrs light): 12/12 - Vehicle:
- methyl ethyl ketone
- Remarks:
- The stability of the test item in the vehicle was analytically verified for up to 2 hours.
- Concentration:
- 50 % test item in MEK for induction and challenge phase
0.5 % DNCB (positive control) for induction and challenge phase - No. of animals per dose:
- 6
- Details on study design:
- TREATMENT PREPARATION AND ADMINISTRATION:
The test item was formulated immediately before each administration in methyl ethyl ketone.
- Induction: The test item in the formulation was applied epicutaneously onto the pre-shaven flank of the animals. This treatment was repeated on
three consecutive days (d1, d2 and d3). The volume administered was 50µl/ear.
- Challange: The test item in the formulation was applied epicutaneously onto the dorsal part of both ears of the animals. This treatment was
repeated on three consecutive days (d15, d16 and d17). The volume administered was 25µl/ear.
The animals were anaesthetized by inhalation of carbon dioxide and sacrificed one day after the last application (d18). The appropriate organs were
then removed. Lymphatic organs (the auricular lymph nodes) were transferred into physiiological saline (PBS).
Investigations:
- weight of lymph nodes
- cell counts in lymph nodes
- stimulation index is calculated by dividing the absolute number of weight or cell counts of the substance treated lymph nodes by the vehicle treated ones.
- ear swelling
- ear weight - Positive control substance(s):
- other: 1-Chloro-2,4-dinitrobenzene (DNCB) CAS-No: 97-00-7
- Statistics:
- When it was statistically reasonable, the values from treated groups were compared with those from the control group(s; vehicle) by a one-way
analysis of variance (ANOVA) when the variances are considered homogeneous according to an homogeneity testing like Cochrans test. Outlying
values in the LN weights were eliminated at a probability level of 99% by Nalimov's method (Statistik für naturwissenschaftliche Berufe, 1982, 88-89).
In addition, for the LLNA/IMDS the smallest significant differentes in the means were calculated by Scheffe's method (Biometrica 40, 1953, 87-104),
which according to Sachs (Angewandte Statistik 6th and 10th edition, Springer Verlag, Berlin, 1978/2002 ) can be used for both equal and unequal
sample sizes. - Positive control results:
- Performed in 2002. The "positive level" which is 1.3 for cell counts has been statistically significant exceeded in the highest dose group (30%).
(Cell index/concentration: 0.88 / 3%; 1.13/ 10%; 1.77/ 30%) - Parameter:
- SI
- Remarks on result:
- other: The "positive level" which is 1.4 for the cell index was statistically significant exceeded after application of 0.5 % DCNB
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: modified LLNA; measurement of cell counts instead of radioactive labeling
- Conclusions:
- Sensitizing property can be excluded after application of 50 % concentration of the test item for induction and challenge.
- Executive summary:
The aim of these investigations was to verify any specific (sensitizing) stimulating potential of the test item as assumed after primary response investigations (Bayer AG, 2003).
A LLNA/IMDS was carried out in female NMRI mice after epicutaneous application of the test item for 3 consecutive days, each onto the flank (induction) and both ears (challenge) of the animals. Application with the positive control compound DNCB led to the effects expected after specific challenge, i.e. significant increase in cell counts and ear swelling compared to primary response. Compared to vehicle treated animals there was a clear increase in cell counts in group 2 (vehicle/test item). This change is of statistical significance and the "positive level" of index 1.4 has been exceeded. In contrast, cell count indices of challenge (group 3, 2x test item) did not reach or exceeded this cut-off. The "positive level" of ear swelling has been exceeded in group 2 and 3. These increases are of statistical significance. A significant increase compared to vehicle treated animals regarding ear weights was detected in these groups, too.
Taken together, no activation of antigen specific cells via dermal route was determined after challenge application of
the test item by the used method.
In conclusion, these results show that the test item has an irritant potential in mice after dermal application of a 50% concentration, while a specific memory development has not been observed. Therefore, a sensitizing property can be excluded after application of 50 % concentration of the test item for induction and challenge. These results are verified by the comparision with the results of the positive control group.
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2003-07-01 to 2003-07-04
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- Principles of method if other than guideline:
- Modified LLNA (IMDS; Integrated Model for the Differentiation of Skin Reactions). Modification refer to the measurement of cell proliferation by cell
counting instead of radioactive labeling. In addition, the acute inflammatory skin reaction is determined to discriminate specific from non-specific
activation of immune competent cells in the draining lymph nodes. Such modifications are also authorized in the Note of Guidance SWP/2145/00 of the CPMP (2001) and OECD guideline 429. - GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, Borchen, Germany
- Strain: Hsd Win: NMRI
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: 26 - 33 g
- Housing: individual
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2
- Humidity (%): 40 - 70
- Air changes (per hr): about 10
- Photoperiod (hrs dark/ hrs light): 12/12 - Vehicle:
- other:
- Vehicle:
- other:
- Vehicle:
- methyl ethyl ketone
- Remarks:
- The stability of the test item in the vehicle was analytically verified for up to 2 hours.
- Concentration:
- 0% , 2 %, 10 % and 50 % test item in MEK
- No. of animals per dose:
- 6
- Details on study design:
- TREATMENT PREPARATION AND ADMINISTRATION:
The test item was formulated immediately before each administration in methyl ethyl ketone.
The test item in the formulation was applied epicutaneously onto the dorsal part of both ears of the animals. This treatment was repeated on three
consecutive days (d1, d2 and d3). The volume administered was 25µl/ear.
The animals were anaesthetized by inhalation of carbon dioxide and sacrificed one day after the last application (d4). The appropriate organs were
then removed. Lymphatic organs (the auricular lymph nodes) were transferred into physiological saline (PBS).
Investigations:
- weight of lymph nodes
- cell counts in lymph nodes
- stimulation index is calculated by dividing the absolute number of weight or cell counts of the substance treated lymph nodes by the vehicle treated
ones.
- ear swelling (before first treatment and before sacrifice)
- ear weight - Positive control substance(s):
- other: no positive control
- Statistics:
- When it was statistically reasonable, the values from treated groups were compared with those from the control group(s; vehicle) by the
Mann-Whitney or Wilcoxon significance test. Outlying values in the LN weights were eliminated at a probability level of 99% by Nalimov's method
(Statistik für naturwissenschaftliche Berufe, 1982, 88-89). In addition, for the LLNA/IMDS the smallest significant differences in the means were calculated by Scheffe's method, which according to Sachs can be used for both equal and unequal sample sizes.
In addition, for the LLNA/IMDS the smallest significant differentes in the means were calculated by Scheffe's method (Biometrica 40, 1953, 87-104),
which according to Sachs (Angewandte Statistik 6th and 10th edition, Springer Verlag, Berlin, 1978/2002 ) can be used for both equal and unequal
sample sizes. - Positive control results:
- The Local Node Assay Test methodology was checked for reliability in a test on female NMRI mice using Alpha Hexyl Cinnamic Aldehyde formulated in different vehicles at the concentrations of 3 %, 10 % and 30 %. The results show that the test item has a clear sensitizing potential.
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: modified LLNA; measurement of cell counts instead of radioactive labeling
- Conclusions:
- Sensitizing property can be excluded after application of 50 % concentration of the test item for induction and challenge.
- Executive summary:
The aim of these investigations was to establish whether there is any specific (sensitizing) or non-specific (irritating) stimulating potential of the test item.
A LLNA/IMDS was carried out in female NMRI mice after epicutaneous application of the test item for 3 consecutive days on both ears. Four groups with 6 female NMRI mice were treated with vehicle, 2 %, 10 % and 50% test item.
The NMRI mice showed an increase in the stimulation indices for cell counts in the highest dose group (50%) compared to control animals after application of the test item the test item. The "positve level" which is 1.35 for cell count indices has been exceeded in the highest dose group.
Taken together, a non-specific (irritating) activation of the cells of the immune system via dermal route was determined after application of 50% test item by the method used. Therefore, the concentration of 10% turned out to be the NOEL for the parameters investigated in this study. A possible skin sensitizing potential covered by the irritancy could be excluded by a challenge experiment. Otherwise the test item has to be classified as a weak skin sensitizer.
Referenceopen allclose all
The body weights of the animals were not affected by any treatment.
The body weights of the animals were not affected by any treatment.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
There are two skin sensitization tests according to OECD 406 available (Bayer AG, 2003 and Bayer AG, 2007).
The aim of the second study (Bayer AG, 2007) was to verify any specific (sensitizing) stimulating potential of the test item as assumed after primary response investigations (Bayer AG, 2003).
The first LLNA/IMDS was carried out in female NMRI mice after epicutaneous application of the test item (72 % active ingredient in solvent) for 3 consecutive days on both ears. Four groups with 6 female NMRI mice were treated with vehicle, 2 %, 10 % and 50% test item.
The NMRI mice showed an increase in the stimulation indices for cell counts in the highest dose group (50%) compared to control animals after application of the test item the test item. The "positve level" which is 1.35 for cell count indices has been exceeded in the highest dose group.
Taken togester, a non-specific (irritating) activation of the cells of the immune system via dermal route was determined after application of 50% test item by the method used. Therefore, the concentration of 10% turned out to be the NOEL for the parameters investigated in this study. A possible skin sensitizing potential covered by the irritancy could be excluded ba a challenge experiment. Otherwise the test item has to be classified as a weak skin sensitizer.
The second LLNA/IMDS was carried out in female NMRI mice after epicutaneous application of 50 % concentration of the test item (72 % active ingredient in solvent) for 3 consecutive days, each onto the flank (induction) and both ears (challenge) of the animals. Application with the positive control compound DNCB led to the effects expected after specific challenge, i.e. significant increase in cell counts and ear swelling compared to primary response. Compared to vehicle treated animals there was a clear increase in cell counts in group 2 (vehicle/test item). This change is of statistical significance and the "positive level" of index 1.4 has been exceeded. In contrast, cell count indices of challenge (group 3, 2x test item) did not reach or exceeded this cut-off. The "positive level" of ear swelling has been exceeded in group 2 and 3. These increases are of statistical significance. A significant increase compared to vehicle treated animals regarding ear weights was detected in these groups, too.
Taken together, no activation of antigen specific cells via dermal route was determined after challenge application of the test item by the used method.
In conclusion, these results show that the test item has an irritant potential in mice after dermal application of a 50% concentration, while a specific memory development has not been observed. Therefore, a sensitizing property can be excluded after application of 50 % concentration of the test item for induction and challenge. These results are verified by the comparison with the results of the positive control group.
Justification for selection of skin sensitisation endpoint:
There are two skin sensitization tests according to OECD 406 available (Bayer AG, 2003 and Bayer AG, 2007).The aim of the second study (Bayer AG, 2007) was to verify any specific (sensitizing) stimulating potential of the test item as assumed after primary response investigations (Bayer AG, 2003). Therefore, the second sensitisation study is selected. Both studies are valid without restrictions (Klimisch score 1).
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the two available animal studies and according to the criteria of EC Regulation 1272/2008 2H-Azepin-2-one, hexahydro-, polymer with 1,6 diisocyanatohexane is not classified as sensitizing to skin.
Classification of the substance concerning respiratory sensitisation is not possible because no data are available for this toxicological endpoint.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
