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EC number: 201-247-9 | CAS number: 80-07-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Valid guideline study under GLP-conditions.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 008
- Report date:
- 2008
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Bis(4-chlorophenyl) sulphone
- EC Number:
- 201-247-9
- EC Name:
- Bis(4-chlorophenyl) sulphone
- Cas Number:
- 80-07-9
- Molecular formula:
- C12H8Cl2O2S
- IUPAC Name:
- 1-chloro-4-(4-chlorobenzenesulfonyl)benzene
- Details on test material:
- - Name of test material: 4,4'-dichlorodiphenyl sulfone
- Physical state: white solid pellets
- Analytical purity: >98.4 %
- Batch No.: LP070811
- Storage condition: at room temperature in the dark
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, UK
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: 286-361 g (males), 192-233 g (females)
- Housing: in solid floor polypropylene cages with stainless steel grid tops and softwood flake bedding (Datesand Ltd, Cheshire, UK); in groups of 5 animals/sex/cage premating, or 1 male and 1 female/cage during the mating period, or 1 mated female/cage during gestation and lactation
- Diet: pelleted diet (Rodent PMI 5002 certified diet, BCM IPS Limited, London, UK), ad libitum
- Water: mains drinking water supplied from polycarbonate bottles, ad libitum
- Acclimation period: 2 weeks
ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 2 °C
- Humidity: 55 ± 15 %
- Air changes: 15 air changes/hour
- Photoperiod: 12 hours dark / 12 hours light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS
The test material was prepared at the appropriate concentrations as a suspension in Arachis oil BP. The stability and homogeneity of the dose formulations were determined. Formulations were shown to be stable for at least 14 days. Samples were taken of each formulation and analysed for DCDPS concentration.
VEHICLE
- Justification for use and choice of vehicle: Arachis oil BP is a standard vehicle in studies of this type
- Concentration in vehicle: 0, 1.25, 3.75 or 12.5 mg/mL
- Amount of vehicle: a dose volume of 4 mL/kg bw was used - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentration of DCDPS in the test material formulations was determined by high performance liquid chromatography (HPLC) using an external standard technique. The test material formulations were extracted with acetonitrile to give a final, theoretical test material concentration of approximately 0.1 mg/mL. Standard solutions of test material were prepared in acetonitrile at a nominal concentration of 0.1 mg/mL. The standard and sample solutions were then analysed by HPLC. The analytical method has been satisfactorily validated in terms of linearity, specificity and accuracy for the purposes of the study.
- Details on mating procedure:
- - M/F ratio per cage: 1:1 within each dose group
- Length of cohabitation: max. 14 days
- Proof of pregnancy: vaginal plug and sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- 42 days
Total observation time up to 54 consecutive days (including a two week maturation phase, pairing, gestation and early lactation for females) - Frequency of treatment:
- once daily
- Duration of test:
- up to 54 consecutive days of dosing
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 5, 15, and 50 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 10 animals
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: based on previous toxicology studies
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS:
- Time schedule: before dosing and up to 5 hours (workdays) or 1 hour (weekend) thereafter
BODY WEIGHT:
- Time schedule for examinations: day 1, weekly thereafter (males); weekly until mating, GD 0, 7, 14, 20, PPD 1 and 4
FOOD CONSUMPTION :
- Food consumption for each group determined and mean daily diet consumption calculated as g food/rat/day: Yes, premating and 3 weeks after and individual for females during pregnancy.
FEED EFFICIENCY:
Body weight gain/feed intake: for periods of measured feed consumption
WATER CONSUMPTION:
Visual observation only
POST-MORTEM EXAMINATIONS:
Full external and internal examination for macroscopic anomalies.
Organ weights: epididymes, testes, liver
Histopathology: coagulation gland, liver, ovaries, pituitary, prostate, seminal vesicles, testes, uterus/cervix, vagina - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination.
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes - Fetal examinations:
- Full external and internal examination for macroscopic anomalies
- Statistics:
- Standard methods such as linear regression, ANOVA, Dunntett's, Mann Whitney U test for parametric values, Chi square and Kruskall Wallis for non parametric data.
- Indices:
- Percent post-implantation loss, live birth index, viability index, sex ratio plus weights and righting reflex on day 4.
- Historical control data:
- Historical control data for the same strain were included in the report.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
none
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOEL
- Effect level:
- 15 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
Mean offspring body weight gain between days 1 and 4 of lactation were statistically significantly reduced for offspring from litters treated with 50 mg/kg bw/day. No such effects were detected in offspring from litters treated with 15 or 5 mg/kg bw/day.
Relevant data are summarised in tabular form in section "Any other information on results incl. tables"
Effect levels (fetuses)
- Dose descriptor:
- other: Reduced body weight gain in pups
- Basis for effect level:
- fetal/pup body weight changes
- Remarks on result:
- not determinable
- Remarks:
- No distinct causal relation is evident for the reduced body weight gain (developmental effect) in pups except the association with maternal toxicity. A plausible hypothesis is to see it as a consequence of effects upon maternal metabolism. The altered metabolism may have limited the ability of the female to provide sufficient nutrition to the offspring.
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Offspring body weight and body weight change
Dose level [mg/kg bw/day] |
Offspring body weight [g] |
Offspring body weight change [g] |
||||
Day 1 |
Day 4 |
Days 1-4 |
||||
Males |
Females |
Males |
Females |
Males |
Females |
|
0 (control) |
7.3 ± 0.9 |
6.8 ± 0.8 |
10.5 ± 1.5 |
9.9 ± 1.5 |
3.2 ± 0.7 |
3.1 ± 0.8 |
5 |
6.8 ± 0.6 |
6.4 ± 0.6 |
9.7 ± 1.3 |
9.0 ± 1.2 |
2.9 ± 0.8 |
2.6 ± 0.7 |
15 |
6.8 ± 0.6 |
6.6 ± 0.5 |
9.3 ± 0.9 |
8.9 ± 0.8 |
2.5 ± 0.5 |
2.4 ± 0.5 |
50 |
7.0 ± 0.7 |
6.6 ± 0.6 |
9.3 ± 1.3 |
8.7 ± 1.2 |
2.3 ± 0.6 * |
2.1 ± 0.7 ** |
All values are mean ± standard deviation of 10 animals
* Significantly different from control group p<0.05
** Significantly different from control group p<0.01
Applicant's summary and conclusion
- Conclusions:
- All doses induced effects in the parental generation, which were significantly adverse in the males. Reduced body weight gain was noted in the offsping of mothers treated at 50 mg/kg bw/day (developmental effect). In the absence of any other treatment related finding in the offspring, reduced body weight gain was considered to be secondary to changes in maternal metabolism, but this can not be finally assessed based on the available data.
- Executive summary:
In a reproduction/developmental toxicity screening study (Safepharm Ltd, 2008), DCDPS (>98.4 %) in arachis oil was administered to 10 Sprague-Dawley rats/sex/dose level by oral gavage (4 mL/kg bw) at dose levels of 0 (vehicle only), 5, 15 or 50 mg/kg bw/day. Rats were dosed with DCDPS for two weeks maturation, pairing and pregnancy up to day 4 post partum, thus a total of 42 days. In the developmental screening part of the study, there were no treatment related effects noted on mortality, clinical aspects, food and water consumption as well as food efficiency, reproductive performance/fertility and offspring litter size and viability. Males treated with 50 mg/kg bw/day showed a reduction in cumulative body weight gain throughout the treatment period and a reduction in weekly body weight gain during the first two weeks of treatment. Offspring from litters treated with 50 mg/kg bw/day showed a reduction in body weight gain considered as developmental effect. At necropsy, enlarged livers were seen in males at 15 mg/kg bw/day and in males and females at 50 mg/kg bw/day. Animals of either sex from all treatment groups showed an increase in liver weight. Dose-dependent centrilobular hepatocyte enlargement was seen in all treated groups. Centrilobular hepatocyte vacuolation was noted at 50 mg/kg bw/day being more prevalent in males. Based on these results, the NOAEL for parental toxicity was established at 15 and 50 mg/kg bw/day for male and female animals, respectively. The NOEL for developmental toxicity/teratogenicity was set at 15 mg/kg bw/day based on reduced body weight gain in the offspring at 50 mg/kgbw/day.
This screening study is acceptable and satisfies the requirement for test guideline OECD 421.
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