Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Teratological studies of zinc ethylphenyldithiocarbamate (ZEPC), a vulcanization accelerator for rubber in rats
Author:
Nakaura S, Tanaka S, Kawashima K, Takanaka A, Omori Y
Year:
1983
Bibliographic source:
J Toxicol Sci 8, 337
Reference Type:
publication
Title:
Fetal toxicity of zinc ethylphenylditioncarbamate (ZEPC) (3.). Mechanism of formation of methemoglobin caused by ZEPC
Author:
Nakaura S, Kawanishi T, Ohno Y, Kawashima K, Tanaka S, Takahashi S, Takanaka A, Omori Y, Matumoto K
Year:
1985
Bibliographic source:
J Toxicol Sci 10, 252

Materials and methods

Principles of method if other than guideline:
For the examination of the effects of zinc ethylphenylthiocarbamate (ZEPC) to the prenatal and postnatal development, gravid rats received 31.2, 62.5, 125 or 250 mg ZEPC/kg bw suspended in olive oil from day 7 to 15 of gravidity by oral gavage.
GLP compliance:
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 bis(N-ethyl-N-phenyldithiocarbamate)

Test animals

Species:
rat
Strain:
not specified
Details on test animals or test system and environmental conditions:
No data.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on exposure:
No data
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
No data
Duration of treatment / exposure:
From day 7 to 15 of gravidity.
Frequency of treatment:
Daily
Duration of test:
No data.
Doses / concentrationsopen allclose all
Dose / conc.:
31.2 mg/kg bw/day (nominal)
Dose / conc.:
62.5 mg/kg bw/day (nominal)
Dose / conc.:
125 mg/kg bw/day (nominal)
Dose / conc.:
250 mg/kg bw/day (nominal)
No. of animals per sex per dose:
No data
Control animals:
not specified
Details on study design:
No data.

Examinations

Maternal examinations:
In a follow up experiment, a haemogram was conducted on rats which received daily doses of 125, 250, 500 or 1000 mg zinc ethylphenyldithiocarbamate/kg bw from day 7 to 9.
Ovaries and uterine content:
No data
Fetal examinations:
Haemogram
Statistics:
No data
Indices:
No data
Historical control data:
No data

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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):
A decrease in the number of erythrocytes, haemoglobin amount and haemotocrit value and an increase in microcyte count were observed in the gravid rats.
Clinical biochemistry findings:
not specified
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:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
effects observed, treatment-related
Description (incidence and severity):
With an increased dose of zink ethylphenylthiocarbamate an increased fetal mortality was observed. A dose of 250 mg zink ethylphenylthiocarbamate was lethal for all fetuses.
Changes in pregnancy duration:
not specified
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
not specified
Other effects:
not specified

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Remarks on result:
other: not specified

Maternal abnormalities

Abnormalities:
effects observed, treatment-related
Localisation:
other: haematogram
Description (incidence and severity):
A decrease in the number of erythrocytes, haemoglobin amount and haemotocrit value and an increase in microcyte count were observed in the gravid rats.

Results (fetuses)

Fetal body weight changes:
effects observed, treatment-related
Description (incidence and severity):
A decreased body weight of the fetuses of the dams of the 62.5 and 125 mg/kg bw group was observed.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): effects observed, treatment-related
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): A decreased body weight of the fetuses of the dams of the 62.5 and 125 mg/kg bw group was observed.
Reduction in number of live offspring:
not specified
Changes in sex ratio:
not specified
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
No external, visceral or skeletal anomalies were found in any of the dose groups examined.
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Description (incidence and severity):
No external, visceral or sceletal anomalies were found in any of the dose groups examined.
Other effects:
effects observed, treatment-related
Description (incidence and severity):
Zinc ethyphenyldithiocarbamate has fetal toxic effecs, though the compound has no teratogenic effects and the fetal death od ZEPC may be due to an action of the agent on the erythrocytes of pregnant rats. It is concluded that methemoglobinemia in pregnant rats may be responsible for the in utero toxicity observed after exposure to ZEPC.

Applicant's summary and conclusion

Conclusions:
Zinc ethyphenyldithiocarbamate has fetal toxic effects (fetal deaths, low body weights, skeletal variations, vhangeds of the haematogram), however no external, visceral or sceletal anomalies were found in any of the dose groups examined.
Executive summary:

For the examination of the effects of zinc ethylphenylthiocarbamate (ZEPC) to the prenatal and postnatal development, gravid rats received 31.2, 62.5, 125 or 250 mg ZEPC/kg bw suspended in olive oil from day 7 to 15 of gravidity by oral gavage. Zinc ethyphenyldithiocarbamate has fetal toxic effects (fetal deaths, low body weights, skeletal variations and changes of the haematogram), however no external, visceral or skeletal anomalies were found in any of the dose groups examined. The toxic effects found may be due to methemoglobinemia.