2,2'-(vinylenedi-p-phenylene)bisbenzoxazole

Toxicity to reproduction

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 from secondary source

Data source

Reference

Reference Type:

secondary source

Title:

Human & Environmental Risk Assessment on ingredients of European household cleaning products .

Author:

HERA risk assessments

Year:

2003

Bibliographic source:

HERA targeted risk assessment . May, 2003

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Reproductive and developmental toxicity study of test material was performed on rats.

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)

EC Number:

248-421-0

EC Name:

Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)

Cas Number:

27344-41-8

Molecular formula:

C28H22O6S2.2Na

IUPAC Name:

Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate

Test material form:

solid

Details on test material:

- Name of test material (IUPAC name): 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonic) acid
- Common name: 4,4'-Bis(2-sulfostyryl)biphenyl
- Molecular formula: C28H20Na2O6S2
- Molecular weight: 562.572 g/mol
- Smiles notation: c1(c2ccc(\C=C/c3c(cccc3)S(=O)(=O)[O-])cc2)ccc(\C=C/c2c(cccc2)S(=O)(=O)[O-])cc1.[Na+].[Na+]
- InChl: 1S/C28H22O6S2.2Na/c29-35(30,31)27-7-3-1-5-25(27)19-13-21-9-15-23(16-10-21)24-17-11-22(12-18-24)14-20-26-6-2-4-8-28(26)36(32,33)34;;/h1-20H,(H,29,30,31)(H,32,33,34);;/q;2*+1/p-2/b19-13-,20-14-;;
- Substance type: Organic

Specific details on test material used for the study:

No data available

Test animals

Species:

rat

Strain:

other: Tif:RAI f (SPF) hybrid

Details on species / strain selection:

No data available

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation:9 weeks
- Weight at study initiation:
- Fasting period before study: Females were caged individually in Macrolon cages containing standardized soft wood bedding material.
- Housing:
- Diet (e.g. ad libitum): standard pelleted rat food (Nafag No. 890; Gossau, Switzerland) ad libitum
- Water (e.g. ad libitum):water ad libitum
- Acclimation period:7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3 °C
- Humidity (%):30-70%,
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): daily cycle of 12 hours light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous solution of carboxymethylcellulose (0.5% w/w).

Details on exposure:

Details on exposure
Test material dissolved in aqueous solution of carboxymethylcellulose (0.5% w/w).
VEHICLE
- Justification for use and choice of vehicle (if other than water): Test material dissolved in aqueous solution of carboxymethylcellulose (0.5% w/w).

- Concentration in vehicle:0,1000mg/kg bw/day
- Amount of vehicle (if gavage): 20ml/kg
- Lot/batch no. (if required): No data available
- Purity: No data available

Details on mating procedure:

- M/F ratio per cage:one male rat was housed with 3 females
- Length of cohabitation: No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:vaginal lavage showed spermatozoa or a vaginal plug was observed; this was designated as gestation day zero
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: [no / yes (explain)]No data available
- After successful mating each pregnant female was caged (how): an individual
- Any other deviations from standard protocol:No data available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

10 days (6 through day 15 of gestation)

Frequency of treatment:

Daily

Details on study schedule:

No data available

Doses / concentrations

Remarks:

0, 1000mg/kg bw/day

No. of animals per sex per dose:

Total :48
0 mg/kg :24 female
1000mg/kg:24 female

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:

BODY WEIGHT: Yes
- Time schedule for examinations:

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

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

OTHER:

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

No data available

Postmortem examinations (parental animals):

SACRIFICE
All animals survived to necropsy on gestation day 21
GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]

HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.

Postmortem examinations (offspring):

SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at [#?] days of age.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:

GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]

HISTOPATHOLOGY / ORGAN WEIGTHS
About one-half of each litter was taken for visceral evaluation by the Wilson slicing technique after fixation. The remaining fetuses from each litter were fixed, cleared with KOH solution and then treated with alizarin red S for examination of skeletal features.

Statistics:

No data available

Reproductive indices:

No data available

Offspring viability indices:

No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Description (incidence and severity):

There were no remarkable cage-side observations during the study.

Dermal irritation (if dermal study):

not specified

Mortality:

no mortality observed

Description (incidence):

No effect on survival of treated rats were observed as compared to control.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No effect on body weight of treated rats was observed as compared to control.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

No effect on food consumption of treated rats was observed as compared to control.

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:

no effects observed

Description (incidence and severity):

All animals survived to necropsy on gestation day 21, except for one dam from the treated group, found dead on gestation day 15. Necropsy revealed no pathological findings. Necropsy of all other animals did not reveal adverse effects or abnormal findings

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):

2.The number of implantation sites and preimplantation losses were comparable in the two groups. Early resorption rate was not affected by treatment, and there were no late resorptions, abortions or dead fetuses. Thus, the number of viable fetuses was comparable in the two groups. Statistical analysis of these endpoints did not show significant differences from the control group.
There was no evidence for an impairment of reproductive functions in animals

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

food consumption and compound intake

histopathology: non-neoplastic

reproductive performance

Remarks on result:

other: No effects on reproductive performance

Target system / organ toxicity (P0)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality / viability:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

body weights were not affected by treatment.

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):

The findings observed during fetal examinations were of equal frequency in the control and treated groups; thus, treatment-related effects on fetal external, visceral, or skeletal development did not occur in this study.

Histopathological findings:

not specified

Other effects:

no effects observed

Description (incidence and severity):

Fetal sex ratios were not affected by treatment.

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not examined

Effect levels (F1)

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

viability

mortality

body weight and weight gain

gross pathology

Remarks on result:

other: No developmental toxic effects observed

Target system / organ toxicity (F1)

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Overall reproductive toxicity

Reproductive effects observed:

not specified

Treatment related:

not specified

Relation to other toxic effects:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

In reproductive and developmental toxicity study , NOAEL was considered to be 1000mg/kg bw/day as no effects on reproductive and developmental parameters were observed . When female rats were treated wtih test material orally.

Executive summary:

In reproductive and developmental toxicity study , femaleTif:RAI f (SPF) hybrid ratsrats were treated wtih test material in dose concentration 0,1000mg/kg orally from day 6 through day 15 of gestation, inclusive.Test materialwas administered by gavage in an aqueous solution of carboxymethylcellulose (0.5% w/w). The control group received the vehicle solution. The dose volume in both groups was 20 ml/kg body weight, based on the daily body weight.24 females in each group, a proven fertile male rat of the same strain was placed in a mating cage with 3 females each. The female was removed and indicated as pregnant if vaginal lavage showed spermatozoa or a vaginal plug was observed; this was designated as gestation day zero.All the animals observed for body weight ,food consumption and mortality. There were no remarkable cage-side observations during the study. Maternal body weights and food consumption were not affected by treatment. All animals survived to necropsy on gestation day 21, except for one dam from the treated group, found dead on gestation day 15. Necropsy revealed no pathological findings. Necropsy of all other animals did not reveal adverse effects or abnormal findings.Three animals in the control group were not pregnant, and one in the treated group died on gestation day15. Thus, the number of pregnant animals with viable fetuses at necropsy was 21 and 23 for the control and treated group, respectively.

The number of implantation sites and preimplantation losses were comparable with the control groups. Early resorption rate was not affected by treatment, and there were no late resorptions, abortions or dead fetuses. Thus, the number of viable fetuses was comparable with control groups. Statistical analysis of these endpoints did not show significant differences from the control group.Fetal sex ratios and body weights were not affected by treatment. The findings observed during fetal examinations were of equal frequency in the control and treated groups; thus, treatment-related effects on fetal external, visceral, or skeletal development did not occur in this study.Hence,NOAEL was considered to be 1000mg/kg bw/day as no effects on reproductive and developmental parameters were observed. When female rats were treated wtih test material orally