Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Description of key information

No chronic toxicity

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
chronic

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 lysozyme enzyme has been widely studied and a specific monograph is available. Two old complete chronic toxicity studies were performed on rats and dogs and are mentioned in the monograph; no details about the test procedures and substance composition are available, nevertheless the outcomes reached can be considered as reliable and representative.

 

Rats weighing an average of 100 g were distributed in groups of 10 males and 10 females each received 500 mg/kg p.o., 5 days a week for 5 months. Further 10 males and 10 females were used as control and treated with physiological saline, p.o. At the end of treatment all animals were sacrificed.

No weight differences were recorded in the treated groups in comparison with the control. Morphological blood studies revealed no differences between the treated and control animals. Glycaemia, azotaemia and the serum proteins remained unmodified.

Anatomical and histopathological examination of the lungs, heart, kidneys, liver and spleen showed no particular changes.

Dogs, i.e. fox terriers aged 1.5-2 years old, were distributed in groups of 4 animals (2 males and 2 females) treated with 100 or 500 mg/kg p.o., 5 days a week for 12 months. A further control group was treated with 5 ml/kg of water, p.o. At the end of treatment all animals were sacrificed. There were no signs of intolerance. Weight differences were the same in the treated groups and in the control one. The haematological and blood chemistry data (RBC, WBC, Hb, platelets, differential WBC, haematocrit, clotting time, total serum proteins, albumin/globulin ratio, glycaemia, azotaemia, electrolytes, chlorides, bilirubinemia, choleasterolemia, alkaline phosphatase, transaminases) did not deviate from normal in the treated and untreated animals, and the same applies to the parameters of liver and kidney functions. The weight of the individual organs confirmed the optimum tolerance to the test substance and the analogous conclusions could be deduced from the histological reports.

In general lysozyme can be regarded as the precursor of lysozyme hydrochloride; the transformation into the salt form does not significantly impact the chronic toxicity potential and it is expected that lysozyme and lysozyme hydrochloride share the same potential breakdown products via physical and biological process. Furthermore, it has to be taken into account that the lysozyme as such can be considered as a conservative representative, based on the greater bioavailability potential. After oral intake the extent of absorption via the gastrointestinal tract is determined by the lipophilicity of the substance that can be considered to be comparable for lysozyme and lysozyme hydrochloride. The oral mucosa has a thin epithelium and rich vascularity, which favour absorption; however, contact is usually too brief for substantial absorption. The following step regards the stomach, in which the strong acid pH conditions carry, in both cases, to the same unfolded enzyme structure, with the same salification grade.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Review of the scientific literature available.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.9 Specific target organ toxicity - repeated exposure section, substances are classified as specific target organ toxicants following repeated exposure by the use of expert judgement, on the basis of the weight of all evidence available, including the use of recommended guidance values, which take into account the duration of exposure and the dose/concentration, which produced the effect(s), and are placed in one of two categories, depending upon the nature and severity of the effect(s) observed.

Classification in Category 2 is applicable, when significant toxic effects observed in a 90-day repeated-dose study conducted in experimental animals are seen to occur within the guidance value ranges as:

- Oral (rat): 10 < C ≤ 100 mg/kg bw/day

The guidance values refer to effects seen in a standard 90-day toxicity study conducted in rats.

No adverse effects were reported in rats administered with 500 mg/kg p.o., 5 days a week for 5 months.

In conclusion, the substance does not meet the criteria to be classified for repeated dose toxicity, according to the CLP Regulation (EC 1272/2008).