Registration Dossier

Administrative data

Endpoint:
chronic toxicity: other route
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: limited documentation; no control group, only one concentration

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1959
Report Date:
1959
Reference Type:
publication
Title:
1,3-Dimethylurea (CAS: 96-31-1), SIDS Initial assessment report for SIAM 17
Author:
OECD SIDS
Year:
2009
Bibliographic source:
Unep publications
Report Date:
2003

Materials and methods

GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,3-Dimethylurea (CAS: 96-31-1), no further data

Test animals

Species:
dog
Details on test animals and environmental conditions:
No data provided.

Administration / exposure

Route of administration:
other: oral, by gavage or via feed
Vehicle:
water
Duration of treatment / exposure:
50-984 days
Frequency of treatment:
20-323 administrations
Doses / concentrations
Remarks:
Doses / Concentrations:
1000 mg/kg bw/day
No. of animals per sex per dose:
11 (10 male, 1 female)
Control animals:
no
Details on study design:
Post-exposure period: no

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
2 dogs died after the 3rd or 9th administration from intercurrent diseases that were not considered related to the test substance (hepatitis, intestinal invagination)
Mortality:
mortality observed, treatment-related
Description (incidence):
2 dogs died after the 3rd or 9th administration from intercurrent diseases that were not considered related to the test substance (hepatitis, intestinal invagination)
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
6 animals lost weigt (about 30 %).
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
All animals showed loss of appetite.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
Some animals showed leucocytosis.
Clinical biochemistry findings:
not specified
Urinalysis findings:
effects observed, treatment-related
Description (incidence and severity):
Haematuria was the most prominent clinical symptom, and was present in all animals. Haematuria was first noted after 3-4 administrations of the test substance. From the 6th study week onwards, bladder epithelia were found in urinary sediments.
Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
All animals showed weakness of hind legs, and 4 animals stiffness of hind legs, wich turned into complete paralysis in one animal after 8 months. 8 of 9 animals had pathological changes in the urinary bladder.
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
3 animals had intestinal inflammation, 3 interstitial nephritis, and 3 pneumonia.
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Thickening of urinary bladder wall, hemorrhages, hypertrophic mucosa, partial loss of epithelia and signs of secondary bacterial infection was observerd. No changes were found in urethrae, ureters, brain, spinal cord or peripheral nerves.
Histopathological findings: neoplastic:
not specified
Details on results:
OTHER FINDINGS
- 7 animals vomited after application of the test substance

Effect levels

Dose descriptor:
LOAEL
Effect level:
1 000 mg/kg bw/day
Basis for effect level:
other: stiffness and paralysis of the legs

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion