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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
genetic toxicity in vivo
Remarks:
Type of genotoxicity: other: adduct formation
Type of information:
other: publication
Adequacy of study:
supporting study
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The data concern a literature study; GLP conditions or Guidelines for testing are not mentioned.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1991
Report Date:
1990

Materials and methods

GLP compliance:
not specified
Type of assay:
other: adduct formation

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
28 days
Frequency of treatment:
once daily

Results and discussion

Additional information on results:
As many as 28 consecutive daily doses of [14C]MOCA at 28.1 µgmol/kg body wt (5 µgCi/day) were administered and rats were euthanized at weekly intervals for 7 weeks. MOCA adduct formation for globin and serum albumin was evaluated by determination of [14C]MOCA covalent binding. The covalent binding associated with globin showed a linear increase over the 28-day exposure period with 342 fmol/mg globin 24 hr after the final dose. More extensive covalent binding was detected for albumin with 443 fmol/mg albumin after the final dose, but increases were not linear. After cessation of dosing, the albumin adduct levels decreased rapidly (t1/2 = 4.6 days) in relation to globin adduct levels (tl/2 = 16.1 days). The MOCA-gIobin adduct tl/2 is consistent with that determined after a single 281 µgmol/kg oral dose of MOCA. Significant differences related to route of administration were detected for 24-hr globin covalent binding with ip > po > dermal. Distribution of undifferentiated [14C]MOCA was highest in the liver at 24 hr with tissue levels for liver> kidney> lung> spleen> testes> urinary bladder. Induction of cytochrome P450 enzymes by administration of phenobarbital (100 mg/kg/day/3 days) resulted in a significant (P < 0.05) increase in MOCA-gIobin adduct formation detected with 33.5 pmol/mg globin for induced rats versus 13.6 pmol/mg globin for control rats.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): positive
Upon administration of 14C MOCA to male rats for 28 consecutive days, adduct formation with globin and albumin was observed.