Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The acute oral LD50 of four close analogues of the test substance was determined to be ≥ 2000 mg/kg bw.

The acute inhalation LC50 (4h) of a close analogue of the test substance was determined to be ≥ 2.25 mg/L air, which was the highest attainable concentration.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Please refer to the read-across justification attached to section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Remarks:
Based on read-across from Cellulase 2000L and endo-1,3-beta-glucanase
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Remarks:
Based on read-across from Hostazym C
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 000 mg/kg bw
Remarks on result:
other: Based or read-across from VR002 Pyrolase HT Cellulase
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Please refer to the read-across justification attached to section 13.
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 3 830 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
not determinable due to absence of adverse toxic effects
Remarks:
Based on read-across from endo-1,3-beta-glucanase
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 2.25 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
not determinable due to absence of adverse toxic effects
Remarks:
Based on read-across from Cellulase 2000L
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
2 250 mg/m³ air
Quality of whole database:
Technically attainable concentrations were below the highest classification limit of the CLP Regulation.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Since no acute toxicity studies are available for the substance itself, read-across is made to close structural analogues of the substance.

 

Acute toxicity: oral

No acute oral study was available for the test substance itself. A very close analogue of the test substance, consisting of a complex substance in which the major enzyme activity is from the cellulase, which is basically the same enzyme as the test substance (Cellulase 2000 L), was tested in an OECD TG 401 acute toxicity limit test (Dupont, 2015). Five male and five female Sprague-Dawley rats were exposure orally to 2000 mg/kg bw/d of the test material. They were observed for 15 days. No mortality, nor overt signs of toxicity were noted throughout the observation period. All animals achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15. The LD50 was determined to be ≥2000 mg/kg bw.

Another study (Calvert Laboratories, 2013) assessed the acute oral toxicity of the structural analogue (source substance) VR002 Pyrolase HT Cellulase, according to OECD 425. Female rats were exposed via the oral route (by gavage) to a single dose (1000 mg/kg) of the test item for 14 days. Clinical signs, weight changes, mortality were observed. No adverse effects were observed and the LD50 was determined to be > 1000 mg/kg bw/day.

An oral toxicity study was carried out with Hostazym C (endo-1,4-beta-glucanase), in compliance with OECD Guideline 401 (EFSA, 2013). Five male and five female rats (strain Charles River Crl:CD BR) were given a single dose of 5 g/kg bw in distilled water by gavage. No treatment-related effect on body weight, food consumption or water consumption and no abnormal behaviour were reported during the observation period (14 days). Necropsy of all animals at the end of the study revealed no findings attributable to treatment with the enzyme.

 

Acute toxicity: inhalation

No acute inhalation study was available for the test substance itself. A very close analogue of the test substance, consisting of a complex substance in which the major enzyme activity is from the test substance (Cellulase 2000 L), was tested in an OECD TG 403 acute toxicity limit test (Dupont, 2015). A dust atmosphere was generated, in which approximately 76% of the particles were respiratory. The highest attainable concentration of 2.25 mg/L did not result in any mortality in five male and five female rats after an exposure of 4 hours. There were also no overt signs of toxicity in relation to clinical signs, body weight, food consumption or gross pathology at necropsy after the 14 day observation period. The LC50 was concluded to be > 2.25 mg/L, the highest attainable concentration.

Justification for classification or non-classification

Based on the available information classification for acute oral or dermal toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008. Based on the fact that there were no treatment related effects in the two inhalation studies at concentrations clearly above the limit for classification for Category 3, nor in both oral studies, it is concluded that classification for acute inhalation toxicity is also not warranted, although this cannot be fully ascertained, because it is technically impossible to test the substance up to the highest classification limit.