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Toxicological information

Neurotoxicity

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Administrative data

Endpoint:
neurotoxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, no guideline applicable (mechanistic data). Possibly usefull for antidote therapy.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1964
Reference Type:
study report
Title:
Unnamed
Year:
1965
Report Date:
1965

Materials and methods

Principles of method if other than guideline:
Not applicable: mechanistic study.
GLP compliance:
no
Remarks:
prior to GLP

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
data on other hydrazine compounds are ignored here

Results and discussion

Applicant's summary and conclusion

Conclusions:
Based on results in mice, pyridoxine, amino-oxyacetic acid or p-dimethylaminobenzaldehyde are possible antidote candidates in case of acute toxicity of MMH. Their relevance and safety should be assessed by a physician.
Executive summary:

Taken from the abstract and limited to MMH (other investigated substances were of the hydrazine family):

The mechanism and site of toxic activity of MMH (methylhydrazine) were investigated by acute toxicity studies in mice, by studying cardiovascular and autonomic effects in dogs, by noting the effect on convulsions of transection of the central nervous system at several levels in dogs, and by evaluating selected protective agents in mice. Four separate mechanisms of action are suggested by differences in pharmacologic activity. MMH manifests its MAO inhibitory activity by intensifying the response to tyramine. MMH convulsions originate in a pre-pontine area. In mice, prevention from the effects of MMH, is achieved by pyridoxine and amino-oxyacetic acid. p-dimethylaminobenzaldehyde, but not p-chlorobenzaldehyde or p-nitrobenzaldehyde, protects against the effects of MMH in mice. However, none of the tested items worked to avoid convulsions and death in rats.