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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study in Japanese without complete English Translation

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid - liquid: suspension
Remarks:
migrated information: dispersion
Details on test material:
Lot/batch No: PAK5633
Purity: 98.3%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
males: 50-52 days
females: from 14 days before mating to day 3 of lactation

terminal kill:
males: days 51-53
females: day 4 of lactation
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 6, 30, 150 or 750 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
12 m/ 12 f
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: 1 day

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHTS: Yes

FOOD CONSUMPTION: Yes
Postmortem examinations (parental animals):
GROSS PATHOLOGY: Yes (see attached file)
HISTOPATHOLOGY: Yes (see attached file)
Statistics:
yes

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Other effects:
effects observed, treatment-related

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
effects observed, treatment-related
Reproductive performance:
not specified

Details on results (P0)

In males, exopthalmos was noted in 2 aimals at 750 mg/kg bw. Transiently lowered food consumption was also noted at 750 mg/kg bw. No changes caused by the substance were noted in terms of body weight, necropsy findings, organ weights, or sperm examination. On histopathological examination, vacuolization of lens fibers and hyperplasia of epithelium lentis were noted in 2 and 1 animal, respectively, at 750 mg/kg bw.

In females, mydriasis was noted at 750 mg/kg bw. Transiently lowered body weithg were evident at 750 mg/kg bw during the pregnancy period and transiently reduced food consumption was noted before mating. No changes caused by the substance were noted with regard to necropsy, organ weights, or histopathological examination.

The individual results are summarised in the attached file Tables and Figures.

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
150 mg/kg bw/day (actual dose received)
Sex:
male/female
Dose descriptor:
LOAEL
Effect level:
750 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: exophthalmos in males; mydriasis in females

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
From this study a NOAEL of 150 mg/kg bw for male and female rats was derived
Executive summary:

In this study performed according to OECD Guideline 421, male and female Sprague Dawley rats were dosed orally via gavage with 0, 6, 30, 150, or 750 mg/kg bw over 50 -52 days (male) and from 14 days before mating to day 3 of lactation (females). terminal kill in males was on days 51 -53 and in females on day 4 of lactation.

In males, exopthalmos was noted in 2 animals at 750 mg/kg bw. Transiently lowered food consumption was also noted at 750 mg/kg bw. No changes caused by the substance were noted in terms of body weight, necropsy findings, organ weights, or sperm examination. On histopathological examination, vacuolization of lens fibers and hyperplasia of epithelium lentis were noted in 2 and 1 animal, respectively, at 750 mg/kg bw.

In females, mydriasis was noted at 750 mg/kg bw. Transiently lowered body weight were evident at 750 mg/kg bw during the pregnancy period and transiently reduced food consumption was noted before mating. No changes caused by the substance were noted with regard to necropsy, organ weights, or histopathological examination.

From this study a NOAEL of 150 mg/kg bw for male and female rats was derived