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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
other: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
2005
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
EFSa scientific report
Justification for type of information:
Justification for Read Across is provided in Section 13 of IUCLID

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Conclusion regarding the peer review of the pesticide risk assessment of the active substance fosetyl
Author:
EFSA
Year:
2005
Bibliographic source:
European Food Safety Authority, 2005. Conclusion on the peer review of the pesticide risk assessment of the active substance fosetyl. EFSA Scientific Report (2005) 54, 1-79.
Reference Type:
secondary source
Title:
EPA memorandum
Author:
EPA
Year:
1990
Bibliographic source:
Second Carcinogenicity Peer Review of Aliette
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
insufficient number of days of exposure
Principles of method if other than guideline:
Eighty (20 per group) mature CFY strain SPF female rats were treated from day 6 to day 15 of pregnancy inclusively by oral gavage of 2.0 mL/100 g of a solution of the test item in sterile distilled water at the following concentrations: 0, 500, 1000 and 4000 mg/kg bw.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
other: CFY

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
2.0 mL/100 g of a solution of the test item in sterile distilled water at the following concentrations: 0, 500, 1000 and 4000 mg/kg bw.
Details on mating procedure:
No data
Duration of treatment / exposure:
From day 6 to day 15 of pregnancy
Frequency of treatment:
Once per day
Duration of test:
20 days.
Doses / concentrationsopen allclose all
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Dose / conc.:
4 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
20 female rats per dose
Control animals:
yes, concurrent no treatment

Examinations

Maternal examinations:
On day 20 of pregnancy all animals were sacrificed, dissected and observed for macroscopic pathological changes in maternal organs.
Fetal examinations:
On day 20 of pregnancy all animals were sacrificed. Live young were examined externally. The pups in each litter were then examined for visceral and skeletal malformations.
Indices:
In the controls, 500 and 1000 mg/kg groups, 1/20 mated animals. All the females from the high dose group were pregnant.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Test item treatment in rats caused maternal toxicity (5/20 pregnant dams died, retarded body weight gain) at the highest dose tested (4000 mg/kg bw/day), when administered orally by gavage from day 6 to day 15 of pregnancy inclusively.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOEL
Effect level:
ca. 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
mortality
body weight and weight gain
early or late resorptions
Dose descriptor:
LOEL
Effect level:
ca. 4 000 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
mortality
body weight and weight gain
early or late resorptions

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
effects observed, treatment-related
Skeletal malformations:
effects observed, treatment-related
Description (incidence and severity):
Delayed ossification

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOEL
Remarks:
developmental toxicity
Effect level:
ca. 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
fetal/pup body weight changes
skeletal malformations
Dose descriptor:
LOEL
Remarks:
developmental toxicity
Effect level:
ca. 4 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
fetal/pup body weight changes
skeletal malformations

Fetal abnormalities

Abnormalities:
effects observed, treatment-related
Localisation:
other: delayed ossification

Overall developmental toxicity

Developmental effects observed:
yes
Lowest effective dose / conc.:
4 000 mg/kg bw/day (nominal)
Treatment related:
yes
Relation to maternal toxicity:
developmental effects occurring together with maternal toxicity effects, but not as a secondary non-specific consequence of maternal toxicity effects
Dose response relationship:
yes

Applicant's summary and conclusion

Conclusions:
NOEL (maternal toxicity) = 1000 mg/kg bw/day
NOEL (development) = 1000 mg/kg bw/day
Executive summary:

The developmental toxicity of the substance was evaluated in an experimental study whereby groups of 20 gravid female CFY rats were administered 2.0 mL/100 g test item in sterile distilled water from day 6 to day 15 of pregnancy inclusively via oral gavage at concentrations of 500, 1000 and 4000 mg/kg bw/day for 20 days, alongside a vehicle control group tested in parallel.

As a result of maternal toxicity at highest dose level, litter weight and mean foetal weight were reduced, total resorptions were increased and delayed ossification of fetuses were observed. At 1000 mg/kg bw/day, it can be said that developmental effects occurred together with maternal toxicity effects, but not as a secondary non-specific consequence of maternal toxicity effects. At 500 and 1000 mg/kg bw/day there were no conclusive effects on either maternal or foetal parameters.

Based on the early resorptions, reduced body weight gain and mortality observed at the highest dose administered of 4000 mg/kg bw/day, the NOEL for maternal toxicity was set at 1000 mg/kg bw/day. Based on the delayed ossification, poor body weight and body weight gains and increased total resorptions of offspring at the highest dose, the NOAEL for developmental toxicity was expressed as 1000 mg/kg bw/day, however, it should be ruled out that it cannot be ruled out that these observations were effects of maternal toxicity.