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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD 414 and GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.3800 (Reproduction and Fertility Effects)
GLP compliance:
yes (incl. QA statement)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity: >99% (lot #3099997 brought by Monsanto Company)

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: methylcellulose
Duration of treatment / exposure:
30 days
Frequency of treatment:
once a day
Doses / concentrations
Remarks:
Doses / Concentrations:
0.3, 1.5 & 3.0
Basis:
nominal conc.
mg/kg bw/day
No. of animals per sex per dose:
20
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
reduced body weight gain for female (gestation days 6-19) at mid and high dose groups.
Oestrous cyclicity (parental animals):
no significant differences
Sperm parameters (parental animals):
no significant differences
Litter observations:
no significant differences
Postmortem examinations (parental animals):
no significant differences at low dose group and control grop
Postmortem examinations (offspring):
no examined
Statistics:
Statistical analyses were performed by a Digital Vax 11/730 computer. All analysis were two-tailed with a minimum significance level of 5%. One way analysis of variance followed by Dunnett's test was used to analize material and fetal data including body weights, food consumptions, number of viable fetuses, implancation sites, and corpora lutea. Mann-whitney U test was used to compare post-implantation loss, dead fetuses, and resorptions. Fetal sex ratios were analyzed using the Chi-Square test. Fisher's Exact test was used to analyze the incidence and number of fetal malformations and variactions utilizing the dam (litter) as the experimaental unit.
Reproductive indices:
inplantation index, gestation index, delivery index, live birth index
Offspring viability indices:
no examined

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
No apperant treatment-related clinical signs were observed at the 0.3 mg/kg/day level. clinical signs of toxicity were observed at the 1.5 and 3.0 mg/kg/day levels and induced labored breathing, rales, few feces, whitish colored mucoid material in the ca
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean maternal body weight and body weight gain were similar between the control and 0.3 mg/kg/day groups. At the 1.5 and 3.0 mg/kg/day levels, statistically significant dose-dependent body weight loss occured during the first three days of dosing (gestati
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Mean maternal body weight and body weight gain were similar between the control and 0.3 mg/kg/day groups. At the 1.5 and 3.0 mg/kg/day levels, statistically significant dose-dependent body weight loss occured during the first three days of dosing (gestati
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
not examined
Other effects:
effects observed, treatment-related
Description (incidence and severity):
Test substance intake: Food consumption calculated as grams/animal/day and grams/kg/day was similar between the control and 0.3 mg/kg/day groups. At the 1.5 mg/kg/day level, food consumption was statistically reduced during the first part of dosing (gestation days 6-9 and 9-12)

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Details on results (P0)

reduced body weight gain for female (gestation days 6-19) at mid and high dose groups.

Effect levels (P0)

Dose descriptor:
NOAEL
Remarks:
Maternal toxicity
Effect level:
0.3 mg/kg bw/day
Based on:
test mat.
Sex:
male/female

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
not examined
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings:
not examined

Details on results (F1)

no observed

Effect levels (F1)

Dose descriptor:
NOEL
Generation:
F1
Effect level:
3 mg/kg bw/day
Based on:
test mat.
Sex:
male/female

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL for maternal toxicity = 0.3 mg/kg/day in rabbit (OECD414)
F1-NOEL = 3.0 mg/kg/day
Executive summary:

NOAEL for maternal toxicity = 0.3 mg/kg/day in rabbit (OECD 414) F1-NOEL = 3.0 mg/kg/day