Registration Dossier

Administrative data

Description of key information

The repeated dose oral toxicity of Lipase has been tested.  The repeated dose inhalation and dermal toxicity were waived based on exposure considerations and the properties of the substance.
The repeated dose oral toxicity was a subchronic toxicity test conducted according to OECD guideline 408 and in compliance with GLP. The conclusion was that the No Observed Adverse Effect Level (NOAEL) in rats was the highest dose level tested - 1080 mg/kg bw/day (based on TOS (Total Organic Solids)).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 080.2 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Toxicological data has been generated within the enzyme producing industry during the last 40 years. Substantial documentation on the safety of the production strains has been generated, and the enzyme test materials are thoroughly characterized. High quality studies for all relevant endpoints for in vivo studies as well as in vitro studies show that industrial enzymes from well-known and well characterized production strains have very similar safety profiles across the catalytic activities. Read-across can therefore be applied for the majority of toxicological endpoints. The database can therefore be considered of high quality.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The repeated dose oral toxicity of lipase has been tested, while the repeated dose inhalation and dermal toxicity were waived.

- The dermal study was waived because of the low likelihood of absorption of enzymes through the skin due to the physico-chemical properties of the enzyme protein.

- The inhalation study was waived because exposure is too low to exert any toxicity. Potential exposure by inhalation to an amount of enzyme, which is toxicologically relevant, is unrealistic due to the stringent work practices and the formulation of enzymes, enforced because of the risk of sensitization by inhalation.

- The repeated dose oral toxicity was a subchronic toxicity test conducted according to OECD guideline 408 (adopted 1998), and in compliance with GLP. The conclusion was that the No Observed Adverse Effect Level (NOAEL) in rats was the highest dose level tested, equivalent to 10 mL of undiluted test material/kg bw/day or 1080 mg Total Organic Solids (TOS)/kg bw/day.

 

Based on repeated dose oral and weight of evidence, lipase does not exert any repeated dose oral, dermal or inhalation toxicity to workers or consumers.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
The inhalation study was waived because exposure is too low to exert any toxicity. Strict exposure controls are based on the more sensitive health effect of respiratory sensitization. Potential exposure by inhalation to an amount of enzyme that is toxicologically relevant is unrealistic due to the stringent work practices and the formulation of enzymes.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
The inhalation study was waived because exposure is too low to exert any toxicity. Strict exposure controls are based on the more sensitive health effect of respiratory sensitization. Potential exposure by inhalation to an amount of enzyme that is toxicologically relevant is unrealistic due to the stringent work practices and the formulation of enzymes.

Justification for classification or non-classification

Based on repeated dose oral study and weight of evidence, lipase does not exert any repeated dose oral, dermal or inhalation toxicity to workers or consumers.