Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Methodology and results insufficient reported

Data source

Reference
Reference Type:
publication
Title:
The toxicology of resin Vulcacite P Extra N accelerator of vulcanization
Author:
Yalkut SI
Year:
1971
Bibliographic source:
Gig. Sanit., 36, 28-31 (in Russian language)

Materials and methods

Principles of method if other than guideline:
For the evaluation of the subchronic/chronic toxicity of zinc ethylphenylthiocarbamate 10 rats each (no information of strain and sex) received by gavage 6 times weekly 500 mg/kg bw for 1.5 months, 100 or 10 mg/kg bw for 4 months and 1 mg/kg bw for 10 months.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Zinc bis(N-ethyl-N-phenyldithiocarbamate)
EC Number:
238-677-1
EC Name:
Zinc bis(N-ethyl-N-phenyldithiocarbamate)
Cas Number:
14634-93-6
Molecular formula:
C18H20N2S4Zn
IUPAC Name:
zinc(2+) bis([ethyl(phenyl)carbamothioyl]sulfanide)
Specific details on test material used for the study:
No data

Test animals

Species:
rat
Strain:
not specified
Details on species / strain selection:
No data
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data

Administration / exposure

Route of administration:
oral: gavage
Details on route of administration:
No data
Vehicle:
not specified
Details on oral exposure:
No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
1.5, 4 or 10 month
Frequency of treatment:
6 times weekly
Doses / concentrationsopen allclose all
Dose / conc.:
500 mg/kg bw/day (nominal)
Remarks:
1.5 month
Dose / conc.:
100 mg/kg bw/day (nominal)
Remarks:
4 month
Dose / conc.:
10 mg/kg bw/day (nominal)
Remarks:
4 month
Dose / conc.:
1 mg/kg bw/day (nominal)
Remarks:
10 month
No. of animals per sex per dose:
10 rats/dose
Control animals:
not specified
Details on study design:
Mortality, body weight, clinical biochemistry and haematological finding and histopathological examination.

Examinations

Observations and examinations performed and frequency:
Mortality, body weight, clinical biochemistry and haematological finding and histopathological examination.
Sacrifice and pathology:
AHistopathological results were reported.

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
At a dosage of 500 mg/kg bw 3 rats died after 32, 34 or 41 days. The other dosages did not cause any deaths.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
At a dose of 500 mg/kg bw the body weight gain was 12% (after 1.5 months) lowever than in the control group, at a dosage of 100 mg/kg bw the body weight gain was 16% (after 2 months) lower than in the control group.
Food consumption and compound intake (if feeding study):
not specified
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):
In the haemogram the both upper dosages caused "strong disorders". With a dosage of 10 mg/kg bw at the end of the thrird months there was a trend towards a reduced erythrocyte number and at the end of the experiment a strong
reticulocytosis was seen. Furthermore, the prothrombin time was decreased after 3 months (administration of 100 mg/kg bw) or 4 months (administration of 10 mg/kg bw).
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
The cytochrome oxidase activity in the liver was decreased after 4 months (100 mg/kg bw), the ceruloplasmin activity was decreased 4 months after administration of 100 mg/kg bw and 3 months after administration of 10 mg/kg bw.
Furthermore, after the administration of 100 mg/kg bw an increase in the catalase index (p <0.05) was observed..
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Slight granular degeneration of liver cells, increased aveolar and histocytic cells in the lungs, peribronchial infiltration, dilatation and hyperemia of the renal vessels, granular degenerationof the tubular epithelium with isolated necroses as well as dilated spleen vessels were observed at a dosage of 100 mg/kg bw and 10 mg/kg bw. At a dosage of 100 mg/kg bw numerous megakaryocytes were found in the spleen pulp.
Histopathological findings: neoplastic:
not specified

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
haematology
histopathology: non-neoplastic
Remarks on result:
other: The oral administration of 1 mg/kg bw over 10 months revealed no effects compared to controls.

Target system / organ toxicity

Critical effects observed:
yes
Lowest effective dose / conc.:
10 mg/kg bw/day (nominal)
System:
haematopoietic
Organ:
kidney
liver
spleen
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
yes

Applicant's summary and conclusion

Conclusions:
The oral administration of 1 mg/kg bw over 10 months revealed no effects. With higher doses haematological and histopathological findings (liver, lung, spleen) were repoted.
Executive summary:

After a subchronic/chronic oral administration of 500 mg/kg bw of zinc ethylphenyldithiocarbamate to rats for 1.5 months some cases of deaths occurred. A dosage of 100 mg/kg bw or 10 mg/kg bw changes in the haemogram, the prothrombin time,and the cytochrome oxidase were observed. Histopathological effects on the liver, lung and kidneys were detected. The oral administration of 1 mg/kg bw over 10 months revealed no effects.