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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Study performed according to currently valid guidelines without restriction.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Deviations:
yes
Remarks:
higher animal number was used to give 20 males and 20 females per group
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid - liquid: suspension
Details on test material:
Dechlorane Plus of 99% purity was suspended in corn oil, an analytical certificate is part of the study report.
Supplied by Occidental Chemical Corporation (Niagara Fall, New York)

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
the aniamls were 6-8 weeks of age at begining of the study and were maintained according to current recommendations at 64 - 79°F and 30-70% humidity, housed individually in steel wire mesh cages. Fluorescent lightning was provided for 12 hours per day.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Concentration, stability, and homogeneity of the test stubstance in vehicle was analytically verified, the formulations in vehicle were prepared weekly, dose levels of 0, 750, 1,500, and 5,000 mg/kg bw were administered daily by gavage
Details on mating procedure:
Mating was performed by housing one female and one male of the same treatment group together for 14 days, evidence of copulation was verified by the presence of a copulatory plug in the vagina or by vaginal lavage with the presence of sperm, the day of copulation was considered gestational day 0.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Homogeneity, stability, and concentration of test substance in vehicle were analytically verified by the sponsor, the results are reported separately.
Duration of treatment / exposure:
Males were treated for at least 63 days with 21 days premating, 14 days of mating, and 28 days after mating. Females were treated for up to 64 days with 21 days premating, 14 days of mating, and throughout gestation. Half of the pregnant females were killed on gestational day 20, the other half was further treated and killed on day 3 of lactation.
Frequency of treatment:
once daily
Details on study schedule:
Groups of 20 males and 20 females were administered the test substance at dose levels of 0, 750, 1,500, or 5,000 mg/kg bw once daily orally by gavage for 21 days before mating and throughout mating and gestation up to 28 days after mating for males, up to day 20 of gestation for 10 females, and up to day 3 of lactation for the remaining 10 females.
Doses / concentrationsopen allclose all
Dose / conc.:
0.75 mg/kg bw/day (nominal)
Dose / conc.:
1 500 mg/kg bw/day (nominal)
Dose / conc.:
5 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
20 males and 20 females per dose
Control animals:
yes, concurrent vehicle
Details on study design:
Half of the pregant females was killed at the end of gestation, the other half was allowed to give birth and the females and the pups were killed on day 3 of lactation.
Positive control:
none

Examinations

Parental animals: Observations and examinations:
Mortality and clinical signs of toxicity twice daily, detailed clinical observation daily, bodyweights every 3-4 days, food consumption weekly, oestrus cycle determination before successful copulation daily, evidence of copulation during mating daily, signs of parturition twice daily at the end of gestation, abnormalities at parturition, litter size, number of stillborn and liveborn pups, pup sex, pup bodyweights and gross malformations and variations as soon as possible after parturition, pup behaviour daily, pup bodyweight and survival on day 4 post partum, the females killed on gestational day 20 were examined at necropsy for location of viable and nonviable foetuses, early and late resorptions, number of corpora lutea, gravid uterine weight, placenta morpholy, foetal sex and weight, gross and visceral malformations and variations, all parental males and females underwent macroscopic pathology examination, the organ weights of epididymides and testes were determined. Pups were killed on day 4 of lactation and examined for gross malformations and variations.
Oestrous cyclicity (parental animals):
recorded during mating until successful copulation, no changes detected
Sperm parameters (parental animals):
not examined
Litter observations:
Pup behaviour, bodyweights, and survival was recorded until necropsy on lactational day 4, the pups were examined for gross malformations and variations, the sex was determined.
Postmortem examinations (parental animals):
All parental animals, males and females, were subjected to full necropsy with macroscopic pathological examination, the weight of epididymidis and testes was determined.
Postmortem examinations (offspring):
Pups killed on lactational day 4 were examined for gross malformations, foetuses of females killed on gestational day 20 were examined for number of live and dead foetuses, early and late resorptions, sex and bodyweight, gross and visceral malformations and variations.
Statistics:
Levene's / ANOVA- Dunnett's / Welch's, Aresin-Square-Root Transformation followed by group pair-wise comparison, Fisher's exact test, Covariate Analysis.
Reproductive indices:
Number of viable and nonviable foetuses, number of early and late resorptions, number of corpora lutea, bodyweights and sex of foetuses, gross and visceral malformations and variations.
Offspring viability indices:
Litter size, number of stillborn and liveborn pups, sex, bodyweights, gross malformations and variations, behaviour daily, and survival up to postnatal day 4.

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not examined
Other effects:
no effects observed

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)

No effects at all were observed.

Effect levels (P0)

Key result
Dose descriptor:
NOEL
Effect level:
>= 5 000 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
clinical signs
body weight and weight gain
food consumption and compound intake
organ weights and organ / body weight ratios
gross pathology
reproductive function (oestrous cycle)
reproductive function (sperm measures)
reproductive performance

Results: F1 generation

General toxicity (F1)

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

Details on results (F1)

No treatment-related effects were observed with respect to viability, sex distribution, bodyweights, gross and visceral malformations and variations, and behaviour up to day 4 after birth.

Effect levels (F1)

Key result
Dose descriptor:
NOEL
Generation:
F1
Effect level:
>= 5 000 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No treatment related effect at all was observed in any sex in any group at any dose level in all parameters examined.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Dechlorane Plus was essentially nontoxic to reproduction in males and females and did not affect embryofoetal and postnatal development of offspring up to a dose level of 5,000 mg/kg bw per day.
Executive summary:

The NOEL for effects on parental animals (males and females) and on embryofoetal and postnatal development was determined at or above the highest dose level of 5,000 mg/kg bw per day.