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Administrative data

Description of key information

A Combined Repeated Dose Toxicity Study study with the Reproductive/Developmental Toxicity Screening Test (OECD TG 422) in rats by the oral route (dietary) of ZMB2 resulted in repeated dose LOAEL value of 60 mgkg/day.  

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
60 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
2

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

Oral route:

A Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test (OECD TG 422) in Sprague-Dawley rats by the oral route (dietary) of ZMB2 resulted in various systemic effects at the lowest dose 1000/900 ppm diet (ca. 60 mg/kg/day, based on study-specific chemical intake data).

Following ECHA (2010) guidance on DNEL calculation, a repeated dose NOAEL value for ZMB2 is estimated as 20 mg/kg bw/day, and equals one-third the LOAEL value. 

Inhalation route:

According to Column 2 of Annex VIII of the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) legislation repeated dose toxicity: inhalation route does not need to be conducted if exposure of humans is unlikely, taking into account the vapour pressure of the substance and/or the possibility of exposure via particles of inhalable size. Although the median particle size diameter of ZMB2 is 96.44 µm with the main fraction of 64 % distributing in the range of 10 to 100 µm; and hence the particle size of ZMB2 is considered inhalable/respirable fraction as defined in EU 481; exposure of ZMB2 to humans is considered minimal due to appropriate Risk Management Measures (RMM) identified in the Chemical Safety Report. In addition, a repeated dose toxicity: oral route study (conducted to OECD TG 422) is available. Therefore, based upon low human exposure potential and available study data, this endpoint is waived.

Dermal route:

According to Column 2 of Annex VIII of the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) legislation repeated dose toxicity: dermal route does not need to be conducted if exposure of humans is unlikely, taking into account any skin contact during production and the rate of absorption through the skin. Exposure of ZMB2 to humans via skin contact is considered minimal due to appropriate Risk Management Measures (RMM) identified in the Chemical Safety Report. In addition, a repeated dose toxicity: oral route study (conducted to OECD TG 422) is available. Therefore, based upon low human exposure potential and available study data, this endpoint is waived.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Well conducted OECD guideline and GLP study.

Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: bone marrow; cardiovascular / hematological: spleen; digestive: salivary glands; glandular: adrenal gland; glandular: thyroids; neurologic: pituitary

Justification for classification or non-classification

A Combined Repeated Dose Toxicity Study study with the Reproductive/Developmental Toxicity Screening Test (OECD TG 422) in rats by the oral route (dietary) of ZMB2 resulted in repeated dose LOAEL value of 60 mgkg/day. 

In accordance with Regulation No 1272/2008 Table 3.9.3 ZMB2 is classified as Category 2 for repeated dose toxicity, based on an effective 28 day effect level in the range of 10 to 100 mg/kg bw/day.