Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study planned
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: levulinic acid

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: not available
- Available non-GLP studies: information on the repeated dose (oral) toxicity of the substance is available from a 16-day study (secondary source: Saito et al. 2017, primary source: Tischer et al. 1942). This information is however, not sufficient for the evaluation of the repeated dose toxicity (at least 28-days) as requested by the Annex IX. The test determined a NOAEL > 2000 mg/kg bw/day. Therefore, it is expected that also after 28 days no severe sever effects will be observed. Consequently, a 90-day study is considered as appropriate for the complete evaluation of the toxicity of the substance after a repeated dose exposure.
- Historical human data: not available
- (Q)SAR: not available
- In vitro methods: not available
- Weight of evidence: no other data is available and a weight of evidence is not applicable.
- Grouping and read-across: no read across data available
- Substance-tailored exposure driven testing: significant exposure may not be excluded

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION
- A reliable short-term toxicity study is not available, however, in a 16-day repeated dose toxicity study (Tischer et al.1942) no severe toxicity effects were reported and the NOAEL was determined as > 2000 mg/kg bw/day. A reliable chornic toxicity study is not available and the substance is not expected to undergo disintegration. The substance is not insoluble or unreactive. Consequently, a 90-day study is considered as appropriate for the complete evaluation of the toxicity of the substance after a repeated dose exposure.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed: OECD 408 guideline methodology

Kenji Saito, Yasuko Hasegawa-Baba, Fumiko Sekiya, Shim-mo Hayashi, Yoshiharu Mirokuji, Hiroyuki Okamura, Shinpei Maruyama, Atsushi Ono, Madoka Nakajima, Masakuni Degawa, Shogo Ozawa, Makoto Shibutani & Tamio Maitani. 2017. Japan Flavour and Fragrance Materials Association’s (JFFMA) safety assessment of food-flavouring substances uniquely used in Japan that belong to the class of aliphatic primary alcohols, aldehydes, carboxylic acids, acetals and esters containing additional oxygenated functional groups, Food Additives & Contaminants: Part A, 34:9, 1474-1484
Tischer RG, Fellers CR, Doyle BJ. 1942. The non-toxicity of levulinic acid. J Am Pharm Assoc. 31:217–220.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Applicant's summary and conclusion