Registration Dossier

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from the SCCP report.

Data source

Reference
Reference Type:
other: secondary source
Title:
OPINION ON PHENYLBENZIMIDAZOLE SULFONIC ACID AND ITS SALTS
Author:
HEALTH AND CONSUMER PROTECTION DIRECTORATE GENERAL
Year:
2006
Bibliographic source:
OPINION ON PHENYLBENZIMIDAZOLE SULFONIC ACID AND ITS SALTS- SCCP/1056/06

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: OECD 414
Qualifier:
according to
Guideline:
other: B.31 of Annex V to Directive 67/548/EEC
Principles of method if other than guideline:
The present study was conducted to determine the reproductive toxicity potential of test chemical when administered orally to rats.
GLP compliance:
not specified
Limit test:
yes
Justification for study design:
No data

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid
Details on test material:
- IUPAC name:Phenylbenzimidazole Sulfonic Acid
- Molecular formula: C13H10N2O3S
- Molecular weight: 274.299g/mol
- Substance type: organic
-Physical state: solid

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Wistar BOR:Wisw (SPFcpb)
Details on species / strain selection:
No data
Sex:
female
Details on test animals and environmental conditions:
Virgin females were used in the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(distilled water)
Details on exposure:
No data
Details on mating procedure:
No data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
day 6 to 15 post coitum
Frequency of treatment:
daily
Details on study schedule:
No data
Doses / concentrationsopen allclose all
Dose / conc.:
0 other: mg/kg bw
Remarks:
Control group
Dose / conc.:
1 000 other: mg/kg bw
Remarks:
Test group
No. of animals per sex per dose:
Total:50
0 mg/kg bw (control group): 25 female rats
1000 mg/kg bw (test group): 25 female rats
Control animals:
yes, concurrent vehicle
Details on study design:
No data

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: No data
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data

BODY WEIGHT: No data
- Time schedule for examinations: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): No data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study):No data
- Time schedule for examinations: No data

OTHER: Following reproductive parameters were examined:
Corpora lutea
Implantations
Resorptions (complete, early and late)
Oestrous cyclicity (parental animals):
No data
Sperm parameters (parental animals):
No data
Litter observations:
No data
Postmortem examinations (parental animals):
Animals were sacrificed on day 20 and necropsied.

GROSS NECROPSY: Yes

HISTOPATHOLOGY / ORGAN WEIGHTS: Yes
Postmortem examinations (offspring):
No data
Statistics:
No data
Reproductive indices:
No data
Offspring viability indices:
No data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Description (incidence and severity):
There were no signs of toxicity in dams.
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No effect was observed on numbers of corpora lutea, implantation sites, and viable fetuses were found.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
1 000 other: mg/kg bw
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
other: No effects was observed on reproductive parameter tested.
Remarks on result:
other: No effect was observed on numbers of corpora lutea, implantation sites, and viable fetuses were found.

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
Did not show any such malformations.
Histopathological findings:
no effects observed
Description (incidence and severity):
Skeletal variations were the same (nature and frequency) in test- and control group.
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Details on results (F1)

Foetuses were weighed, inspected macroscopically for external malformations and prepared for inspection for visceral and skeletal malformations (by transverse section and double staining respectively). They did not show any such malformations. Skeletal variations were the same (nature and frequency) in test- and control group.

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 000 other: mg/kg bw
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects observed on foetuses.
Remarks on result:
other: No developmental toxicity was observed

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified

Any other information on results incl. tables

Parameters

Control

Test

Total

Mean

Total

mean

Animals

 

 

litter

%

 

Litter

%

Total

25

-

-

25

-

-

pregnant

23

-

-

24

-

-

Corpora lutea

279

12.1

-

269

11.2

-

Implantations

260

11.0

-

233

9.7

-

Resorptions

Complete

0

0

0*

1

0.04

0.3*

Early

6

0.26

2.5*

5

0.21

1.9*

Late

3

0.13

1.2*

3

0.13

1.2*

Foetuses

Dead

0

0

0*

0

0

0*

Live

251

10.9

96.3*

224

9.3

96.6*

Male

128

5.6

50.3**

132

5.5

58.4**

Female

123

5.3

49.7**

92

3.8

41.6**

*) relative to number of implantations (avg. of individual dams)

**) relative to number of live foetuses (avg. of individual dams)

Applicant's summary and conclusion

Conclusions:
Under the condition of this study, the no-observed-adverse-effect level (NOAEL) for dams and foetuses was considered to be 1000 mg/kg bw.
Executive summary:

The present study was conducted to determine the reproductive toxicity potential of test chemical when administered orally to rats. Virgin female rats were used for the study. Two dose groups (25 animals each) were used, one test- (1000 mg/kg bw) and one control group (0 mg/kg bw). They were dosed from day 6-15 post coitum and kept off-dose from day 16-19. There were no signs of toxicity in dams. Animals were sacrificed on day 20 and necropsied. Reproductive parameters were examined [viz.no. of corpora lutea, no. of implantations and resorptions (complete, early and late)]. Foetuses were weighed, inspected macroscopically for external malformations and prepared for inspection for visceral and skeletal malformations (by transverse section and double staining respectively). They did not show any such malformations. Skeletal variations were the same (nature and frequency) in test- and control group. No effect was observed on numbers of corpora lutea, implantation sites, and viable fetuses were found. Therefore, under the condition of this study, the no-observed-adverse-effect level (NOAEL) for dams and foetuses was considered to be 1000 mg/kg bw.