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Toxicological information

Repeated dose toxicity: other routes

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Administrative data

Endpoint:
chronic toxicity: other route
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Does not meet important criteria of today standard method; documentation insufficient for assessment.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1978

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Di-(4-aminophenyl)-methane (MDA), purified or crude; no more data.

Test animals

Species:
dog
Strain:
Beagle
Sex:
female

Administration / exposure

Route of administration:
other: oral by gelatine capsules
Vehicle:
corn oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
47-86 months (4-7 years)
Frequency of treatment:
3 days/week (with occasional pauses)
Doses / concentrations
Remarks:
Doses / Concentrations:
70 mg/day
No. of animals per sex per dose:
4-5
Control animals:
no
Details on study design:
Post-exposure period: See Remarks

Examinations

Sacrifice and pathology:
Moribund dogs, and those that survived until the end of the experiment (7.2 yr), were sacrificed, and subjected to post-mortem examination.  Various organs were examined for micropathological changes.
Other examinations:
Cytoscopic examinations were started after 2 yr and continued at 15 month intervals. After 4.5 yr clinical chemical tests were performed on 3 dogs of each group, and were then conducted at intervals of 4 months or more frequently as indicated.

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Purified and crude MDA produced similar effects. There was occasional body weight

reduction followed by prompt recovery while treatment was interrupted. There was

moderate to severe gross and histopathological changes in the liver. The lesions ranged from enlarged liver cells and slight structural changes to degeneration, portal fibrosis, liver cell necrosis, haemosiderosis, cell infiltration of the portal areas, dilated bile ducts and thickened bile. Less severe effects were 

seen in the kidneys and spleen, and occasionally in other organs. Tumours of the

urinary bladder or liver did not occur. There was no specific effect on blood

sugar, blood urea nitrogen, creatinine, uric acid, total protein, albumin, and only a questionable effect on alkaline phosphatase activity.

Applicant's summary and conclusion