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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Hyperpolarized Pyruvate (13C) Injection, INVESTIGATOR’S BROCHURE
Author:
not stated
Year:
2020
Bibliographic source:
IB Edition Number: 4.0
Release Date: 23 March 2020

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
no guideline available, but well documented study.
GLP compliance:
not specified
Type of assay:
mammalian bone marrow chromosome aberration test

Test material

Constituent 1
Chemical structure
Reference substance name:
Pyruvic acid
EC Number:
204-824-3
EC Name:
Pyruvic acid
Cas Number:
127-17-3
Molecular formula:
C3H4O3
IUPAC Name:
2-oxopropanoic acid
Test material form:
liquid
Specific details on test material used for the study:
Parapyruvate/lactone in TRIS solution was formulated according to the user instruction,
assuming the stock solution comprised concentrations of 10 mg/ml for each of the main
components, parapyruvate and lactone. However, the certificate of analysis showed that the
stock solution contained 8.6 mg/ml parapyruvate and 8.19 mg/ml lactone. The difference
between the target assay value and the observed assay value was attributed to increased water
content in the dry dispensed substance. Accordingly, the actual concentrations for parapyruvate
and lactone were approximately 14-18% less than expected.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
From a range finding experiment, the nominal dose of 200 mg/kg was considered a suitable maximum dose for
the Micronucleus Experiment. Two lower nominal doses of 60 and 20 mg/kg were also
administered. No substantial difference was observed between males and females in the Range-
Finder, therefore male animals only were used in the Micronucleus Experiment.

Administration / exposure

Route of administration:
infusion
No. of animals per sex per dose:
6 per group
Positive control(s):
cyclophosphamide 20 mg/kg

Results and discussion

Test results
Key result
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Positive controls validity:
not specified

Applicant's summary and conclusion

Conclusions:
It is concluded that Parapyruvate/lactone in TRIS solution did not induce micronuclei in the
polychromatic erythrocytes of the bone marrow of male rats treated up to the nominal dose of 200 mg/kg (the maximum practicable dose) following both 24 and 48 h sampling under the conditions of this assay.
Executive summary:

No clinical signs were observed in the Micronucleus Experiment. Bone marrow smears were prepared from sacrificed animals approximately 24 and 48 h post-treatment.