Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (respiratory tract)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
60 ng/m³
Most sensitive endpoint:
sensitisation (respiratory tract)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Worker DMEL, acute short-term as well as long-term inhalation exposure:


Potential occupational exposure to levels of enzyme, which is toxicologically relevant, is unrealistic due to the stringent work practices and adherence to the voluntary Occupational Exposure Guidelines at or below the established ACGIH (www.acgih.org, the American Conference of Governmental Industrial Hygienists) exposure limit value of 60 ng/m3, based on pure enzyme protein for the benchmark enzyme Subtilisin.


Worker DMEL has been discussed and concluded by the involved industry in a recent publications (see reference list) and a limit of 60 ng/m3, expressed in pure enzyme protein, was suggested (Basketter et al, 2010) in line with the established ACGIH threshold limit value.


 


Worker DNEL, acute short-term as well as long-term dermal exposure:


Investigations of percutaneous absorption of peptides, proteins and other molecules of large size revealed that percutaneous absorption of proteins is extremely low and of no toxicological relevance (Basketter et al, 2012 a and b). This is further supported by the physico-chemical data of monoamine oxidase. This substance is a protein with a molecular weight above 50,000 D, has a low logPow value (<0), indicating that it has no bioaccumulation potential and can be anticipated to be readily biodegraded. Thus, systemic exposure following enzyme exposure at occupational exposure levels is without toxicological significance. Non-proteases, such as monoamine oxidase, lack the potential to be skin and eye irritants.


 


References


Basketter, D., Berg, N., Broekhuizen, C., Fieldsend, M., Kirkwood, S., Kluin, C., Mathieu, S. and Rodriguez, C., 2012a. Enzymes in cleaning products: an overview of toxicological properties and risk assessment/management. Regulatory Toxicology and Pharmacology, 64(1), pp.117-123.


Basketter, D., Berg, N., Kruszewski, F.H., Sarlo, K. and Concoby, B., 2012b. The toxicology and immunology of detergent enzymes. Journal of immunotoxicology, 9(3), pp.320-326.


Basketter, D.A., Broekhuizen, C., Fieldsend, M., Kirkwood, S., Mascarenhas, R., Maurer, K., Pedersen, C., Rodriguez, C. and Schiff, H.E., 2010. Defining occupational and consumer exposure limits for enzyme protein respiratory allergens under REACH. Toxicology, 268(3), pp.165-170.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (respiratory tract)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
15 ng/m³
Most sensitive endpoint:
sensitisation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
sensitisation (respiratory tract)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Consumer DMEL, acute short-term as well as long-term inhalation exposure, systemic and local:


 


The risk to consumers is considered very low and regarded as toxicologically insignificant (Basketter et al, 2010, Basketter et al, 2012 a and b). Consumer DMEL has been discussed among the enzyme allergy specialists from enzyme and detergent manufacturers and it was concluded by the involved industry partners in a recent publication and the limit of 15 ng/m3 was suggested (Basketter et al, 2010).


 


Consumer DNEL, acute short-term as well as long-term dermal exposure:


 


Investigations of percutaneous absorption of peptides, proteins and other molecules of large size revealed that percutaneous absorption of proteins is extremely low and of no toxicological relevance (Basketter et al, 2012 a and b). This is further supported by the physico-chemical data of monoamine oxidase. This substance is a protein with a molecular weight above 50,000 D, has a low logPow value (<0), indicating that it has no bioaccumulation potential and can be anticipated to be readily biodegraded. Thus, systemic exposure following enzyme exposure at occupational exposure levels is without toxicological significance. Non-proteases, such as monoamine oxidase, lack the potential to be skin and eye irritants.


 


Consumer DNEL, acute short-term as well as long-term systemic oral exposure:


 


CDX-616 has not been engineered for gastric stability and would be digested/hydrolyzed when ingested. Like all proteins, enzymes that have not been engineered for low pH and/or gastric stability, will denature or degrade into amino acids.


 


References


 


Basketter, D.A., Broekhuizen, C., Fieldsend, M., Kirkwood, S., Mascarenhas, R., Maurer, K., Pedersen, C., Rodriguez, C. and Schiff, H.E., 2010. Defining occupational and consumer exposure limits for enzyme protein respiratory allergens under REACH. Toxicology, 268(3), pp.165-170..


 


Basketter, D., Berg, N., Broekhuizen, C., Fieldsend, M., Kirkwood, S., Kluin, C., Mathieu, S. and Rodriguez, C., 2012a. Enzymes in cleaning products: an overview of toxicological properties and risk assessment/management. Regulatory Toxicology and Pharmacology, 64(1), pp.117-123..


 


Basketter, D., Berg, N., Kruszewski, F.H., Sarlo, K. and Concoby, B., 2012b. The toxicology and immunology of detergent enzymes. Journal of immunotoxicology, 9(3), pp.320-326.