Registration Dossier

Administrative data

Description of key information

The key subacute toxicity study (oral) was carried out according to EU Method B.7 and OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents). The results indicate the very low toxicity. Even at a dose of 1000 mg/kg daily administered for 4 weeks the liver as the main target organ is only slightly affected. All changes are reversible after the end of exposure to unphysiologically high levels of test item. No adverse effects were observed at 215 mg/kg bw/day.
According to REACH Annex VIII column 1 and 2 experimental studies with dosing via the inhalation and dermal route were waived. The sub-chronic toxicity study requirement according to REACH Annex IX was waived based on a weight of evidence approach.
Repeated dose toxicity was previously reviewed by the European Commission Scientific Committee on Food, the EFSA Panel on Additives and Products or Substances used in Animal Feed, the US FDA and the UK Food Standards Agency Expert Group on Vitamins and Minerals. An OECD SIDS review concluded that Nicotinamide is essential for human and animal health and that based on the available information, the substance does not present a hazard to human health.
The weight of evidence assessment revealed a human NOAEL in the range of 25 mg/kg bw/day. An uncertainty factor of 2 has been used to allow for the fact that adults may eliminate Nicotinamide more slowly than the study groups, many of which were children, and that data for children would not reflect the full extent of intersubject variability that could occur in an older population. The upper level for Nicotinamide is established at 12.5 mg/kg bw/day or approximately 900 mg/day for adults.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
repeated dose toxicity: oral
Remarks:
other: Weight of evidence approach
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Justification for data waiving:
other:
Qualifier:
no guideline followed
Principles of method if other than guideline:
Assessment of all available, relevant, adequate and reliable animal and human data.
GLP compliance:
no
Dose descriptor:
NOAEL
Effect level:
12.5 mg/kg bw (total dose)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: The upper level for nicotinamide is established at 12.5 mg/kg bw/day or approximately 900 mg/day for adults (EFSA, 2006).
Critical effects observed:
not specified
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
12.5 mg/kg bw/day
Study duration:
chronic
Species:
other: human
Quality of whole database:
European Food Safety Authority, 2006.

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

Justification for classification or non-classification

Based on the data available the substance is not classified and labeled according to Regulation 1272/2008/EEC (CLP) and Directive 67/548/EEC (DSD).