Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

The study does not need to be conducted if pre-natal developmental toxicity information are available.


Justification for selection of Effect on fertility via oral route:
The study does not need to be conducted if pre-natal developmental toxicity information is available.

Effects on developmental toxicity

Description of key information
Lysozyme did not show teratogenic effects and/or developmental toxicity in both mice and rabbits.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

The lysozyme enzyme has been widely studied and a specific monograph is available. An old complete developmental toxicity study was performed and mentioned in monograph; no details about the test procedures and substance composition are available, nevertheless the outcomes reached can be considered as reliable and representative.

In general lysozyme can be regarded as the precursor of lysozyme hydrochloride; the transformation into the salt form does not significantly impact the reproductive 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.

Twenty gravid mice and ten gravid rabbits were administered with 200 mg/kg p.o. during the organogenetic period, i.e. from gestation days VI to XV and VI to XVIII, respectively. A second group of ten rabbits was treated with physiological saline, as control.

At the end of treatment all animals were sacrificed and carcass section was performed with a determination of the number of foetus, weight, macroscopic appearance and implantation sites. Subsequently, the foetus were sacrificed and stained with alizarin, after which they were examined for anomalies in the thoracic and abdominal lumen and the skeleton. This revealed that the test substance does not have teratogenic action, the foetus were normal in weight, number and implantation sites, and the same applied to resorption or skeletal structure.

Justification for classification or non-classification

According to the CLP Regulation (EC 1272/2008), 3.7 Reproductive toxicity section, reproductive toxicity includes adverse effects on sexual function and fertility in adult males and females, as well as developmental toxicity in the offspring.

Lysozyme did not show teratogenic effects and/or developmental toxicity in both mice and rabbits, thus the information available bring to a conclusion not sufficient for a classification, according to the CLP Regulation (EC 1272/2008).

Additional information