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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The study does not fully comply with the current version of the test guideline (OECD 414) due to the dosing period (GD 6-15). Litter numbers were below 16 in all groups.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 25 inseminated Long-Evans rats were administered Triflumuron once daily by oral gavage at doses of 0, 10, 30 or 100 mg/kg bw/day from the 6th to the 15th day of gestation. The rats body weights, appearance and behaviour were recorded for maternal toxic effects; the fetuses (delivered by cesarean section on the 20th day of gestation) were examined for morphological abnormalities.
GLP compliance:
no
Remarks:
The study was performed before GLP principles were compulsory.

Test material

Constituent 1
Chemical structure
Reference substance name:
2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide
EC Number:
264-980-3
EC Name:
2-chloro-N-[[[4-(trifluoromethoxy)phenyl]amino]carbonyl]benzamide
Cas Number:
64628-44-0
Molecular formula:
C15H10ClF3N2O3
IUPAC Name:
3-(2-chlorobenzoyl)-1-[4-(trifluoromethoxy)phenyl]urea
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Long-Evans
Remarks:
FB 30
Details on test animals or test system and environmental conditions:
Each test group consisted of 25 inseminated rats (2,5 - 3,5 months old, 185-200 g). The rats were housed singly in Type II Makrolon cages under standardized conditions, with 12 hours of electric light daily, at a room temperature of 20 to 23°C and an average relative humidity of 60%. They were fed pelletized Altromin R chow and tap water ad Iibitum.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% aqueous Cremophor emulsion
Details on exposure:
Female rats each received a daily oral dose of the test substance from Gestation Day 6 to 15 (total of 10 doses), administered by gavage. The test compound was applied at a constant volume of 10 mL/kg bw.
Analytical verification of doses or concentrations:
no
Details on mating procedure:
Untreated male and virgin female rats were mated overnight in a ratio of 1 male to 2 females per Type III Makrolon cage. Vaginal smears were obtained on the morning after mating. If sperm was seen to be present in the smear, this day was considered to be Gestation Day 0 for the respective female.
Duration of treatment / exposure:
10 days
Frequency of treatment:
Once daily
Duration of test:
Animals were sacrificed on GD 20.
Doses / concentrationsopen allclose all
Dose / conc.:
10 mg/kg bw/day
Remarks:
Low dose group
Dose / conc.:
30 mg/kg bw/day
Remarks:
Mid dose group
Dose / conc.:
100 mg/kg bw/day
Remarks:
High dose group
No. of animals per sex per dose:
Each dose group comprised of 25 female rats.
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
Clinical signs and body weight were determined daily. Gross necropsy performed at sacrifice.
Fetal examinations:
- Thorough inspection of all fetuses for external anomalies and alterations;
- Measurement of litter weight and of average fetus weight per Iitter;
- Determination of the sex of each fetus;
- Examination of a number of fetuses for visceral malformations by our modification (1) of the WILSON technique (2)
- Evisceration of the remaining fetuses and examination of the abdominal and thoracic organs, followed by clearing of the fetuses with diluted potassium hydroxide solution, staining of the bone system with Alizarin Red S, and assessment of the bone system.
Statistics:
The parameter values were tested for statistical significance by the following methods:

a) Non-parametric ranking method described by WILCOXON (U test of WILCOXON, MANN and WHITNEY) for weight gains, number of implantations, number of fetuses, number of resorptions, fetus weight, placenta weight.

b) Chi-square test (correction of YATES) for number of fetuses with bone alterations, number of fetuses with anomalies, number of stunted fetuses.

c) Either chi-square test (correction of YATES) or FISHER exact test, depending upon the expected frequency, for quotas of fertilized and pregnant rats.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Description (incidence and severity):
Oral administration of the test item at doses of up to and including 100 mg/kg bw/day was tolerated by the dams without having any adverse effects on their physical appearance and behavioural patterns.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
Treatment had no effect on average weight gains. The results are attached below in tabular form.
Gross pathological findings:
no effects observed
Description (incidence and severity):
Observed effects were not due to administration of the test item.
Other effects:
no effects observed
Description (incidence and severity):
No effect on physical appearance. The results are attached below in tabular form.

Maternal developmental toxicity

Changes in number of pregnant:
no effects observed
Description (incidence and severity):
All fertilized rats in all groups were pregnant at scheduled sacrifice. The results are attached below in tabular form.

Effect levels (maternal animals)

Key result
Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other:

Maternal abnormalities

Key result
Abnormalities:
no effects observed

Results (fetuses)

Fetal body weight changes:
no effects observed
Changes in litter size and weights:
no effects observed
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Details on embryotoxic / teratogenic effects:
Dose levels up to and including 100 mg/kg did not show any signs of having either embryotoxic or teratogenic effects. The data show that there were no biologically significant differences between the treated groups and the controls with respect to the following parameters: Implantation quota, Litter size, Resorption quota, Average fetus weight, Average placenta weight, Incidence of stunted fetuses (weighing less than .3 grams), Frequency of fetuses with slight alterations of bone development, Malformation quota. Results are attached below in tabular form.

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other:

Fetal abnormalities

Key result
Abnormalities:
no effects observed

Overall developmental toxicity

Key result
Developmental effects observed:
no

Applicant's summary and conclusion

Conclusions:
A prenatal developmental toxicity study was performed in the rat (25/group) using gavage dose levels of 10, 30 and 100 mg/kg bw/d. Triflumuron showed no maternal toxicity or effects on embryonic and fetal development (NOAEL = 100 mg/kg bw/day).
Executive summary:

Triflumuron was evaluated for maternal compatibility and for embryotoxic and/or teratogenic effects in a study on rats dosed orally with the test compound from Gestation Day 6-15.  Groups of 25 rats (FB 30 strain) were treated with the following dose levels:


Control group: 0 mg/kg bw/d (0.5 % aqueous Cremophor emulsion)


Low dose group: 10 mg/kg bw/d triflumuron


Mid dose group: 30 mg/kg bw/d triflumuron


High dose group: 100 mg/kg bw/d triflumuron


The test compound was applied dissolved in a 0.5% aqueous Cremophor emulsion, at a constant volume of 10 ml/kg bw. Doses of up to and including 100 mg/kg bw/d were tolerated by the mothers without inducing any signs of toxicity. Doses of up to and including 100 mg/kg bw/d had neither embryotoxic nor specific teratogenic effects. In summary, triflumuron applied at doses of up to and including 100 mg/kg bw/d did not have any untoward effects either on the mothers or on embryonic and fetal development. Maternal and developmental NOAELs of 100 mg/kg bw/d are therefore determined for this study.