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EC number: 421-920-2 | CAS number: 154862-43-8
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Effects on fertility
Description of key information
Subacute NOAEL (parental/F1): >1000 mg/kg bw/day (OECD 421/GLP)
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Limit test:
- no
- Specific details on test material used for the study:
- TEST ITEM NAME: 3,9-bis[2,4-bis(1-methyl-1-phenylethyl)phenoxy]-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Dover Chemical Corporation, Lot No. 46D030816
- Expiration date of the lot/batch: March 08, 2017
- Purity: 99.3%
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In original container in a dry/cool, well ventilated place.
- Solubility and stability of the test substance in the solvent/vehicle: stable in vehicle for 4 hours. - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 11 to 13 wks
- Housing: individually, except during the mating period. During the mating period, the rats were housed in groups of 2 rats/cage (one male plus one female). Confirmed mated female rats were caged individually, and nesting material was provided from 14th day of gestation. During the study, the rats were housed in solid floor polypropylene rat cages (size: 41 x 28.2 x 18 cm). Each cage was fitted with a stainless steel top grill having provision for keeping a polypropylene water bottle with stainless steel drinking nozzle. The bottom of the cages were layered with clean sterilized rice (paddy) husk as the bedding.
- Diet (e.g. ad libitum): standard rodent pellet feed (Teklad Certified Global 16% Protein Rodent diet manufactured by Envigo, USA) ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 24 deg C
- Humidity (%): 64 - 67%
- Air changes (per hr): 20-21
- Photoperiod (hrs dark / hrs light): 12 / 12 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The test dose formulations were prepared every day prior to dosing and were used within 4 hours of preparation. The prepared formulation was kept on a magnetic stirrer in order to maintain a homogeneous preparation. The dose volume was 10 mL/kg body weight.
- Details on mating procedure:
- Each female was placed with a single male from the same dose level until copulation occurred or 2 weeks had elapsed. Each morning, the females were examined for the presence of sperm and the ‘day 0’ of pregnancy was recorded. Day 0 of pregnancy was defined as the day on which sperm was observed in the vaginal smears of rats.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentration and homogeneity of the test item in the dose formulation was analysed using a validated HPLC method once before initiation of treatment and twice during treatment period. Dose formulations were found to be within the acceptance level of ± 15% of nominal concentration demonstrating that the prepared concentrations were as intended by the study plan and %CV was less than 10, suggesting that the prepared formulations were homogeneously mixed.
- Duration of treatment / exposure:
- Dosing of both the sexes was initiated 2 weeks prior to mating and continued during the mating period. After mating, the male rats were further dosed up to and including the day before scheduled sacrifice (after approximately 80% of the females had delivered ). Females were further dosed during pregnancy and up to post-partum day 3.
- Frequency of treatment:
- once daily, seven days a week, at approximately the same time each day
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 15 males and 15 females per group
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- The dose levels were selected based on the results of 14-day dose range finding study (JRF Study N° 410-1-04-14642), in which no test item related effect was observed in high dose (i.e., 1000 mg/kg b. wt./day) on body weight, feed consumption and organ weight.
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Animals were observed twice a day for mortality and morbidity
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: All animals were observed twice a day for visible clinical signs during the treatment period.
BODY WEIGHT: Yes
- Time schedule for examinations: Body weight of all the male animals were recorded on the first day of dosing and at weekly interval thereafter and at death. Body weight of all female animals was recorded on first day of dosing and at weekly interval during pre-mating and mating period. During gestation period, female animals were weighed on gestation days 0, 7, 14 and 20. During lactation period, female animals were weighed within 24 hours of parturition (day 0 post-partum), post-partum day 4 (i.e., lactation day 4) and at death.
FOOD CONSUMPTION:
- Feed consumption of all male animals was measured weekly during pre-mating and post-mating period. For female animals, during pre-mating period feed weights were recorded at weekly interval. During gestation period, feed weights were measured on days 0, 7, 14 and 20 and during lactation period, feed weights were measured on lactation days 0 and 4. Feed consumption was not measured during mating period. - Litter observations:
- Each litter was examined as soon as possible after delivery to establish the number of pups, sex of pups, stillbirths, runts and the presence of gross anomalies. Pups which were found dead in the study were weighed and subjected to post-mortem examination.
Individual pup body weight was recorded on lactation days 0 and 4. - Postmortem examinations (parental animals):
- All animals were subjected to full gross necropsy. At the time of sacrifice, the testes and epididymis of all adult male animals were weighed. During sacrifice, number of corpora lutea and implantation sites were recorded for each dam.
Detailed histological examination was performed on the ovaries, testes and epididymis of the animals from the high dose group and the control group. - Postmortem examinations (offspring):
- All pups were subjected to gross pathological examination.
- Statistics:
- Data such as body weight, body weight change, feed consumption, uterine data (number of implantation, number of corpora lutea, the mean number and percent of pre-implantation, post-implantation and post-natal loss), litter parameters (number and weight of male pups, female pups, total pups (male + female)), duration of gestation and pre-coital interval were analysed using Bartlett’s test of homogeneity of variance. If the result was not significant then analysis of variance (ANOVA) was carried out and if the results was significant then t-test was carried out. If ANOVA was significant then Dunnett’s multiple comparison tests was carried out.
Data such as mortality rate, gestation index, parturition index, pups survival index, live birth index and fertility index were analyzed using Chi-Square test. - Reproductive indices:
- male fertility index, female fertility index, gestation index, parturition index and mating index, gestation period and pre-coital interval, pre-implantation loss, pre-natal (post-implantation) loss, post-natal loss.
- Offspring viability indices:
- live pups index and live birth index, survival / mortality index
- Clinical signs:
- no effects observed
- Mortality:
- mortality observed, non-treatment-related
- 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
- Histopathological findings: non-neoplastic:
- no effects observed
- Reproductive performance:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed at limit dose of 1000 mg/kg/day
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, non-treatment-related
- Body weight and weight changes:
- no effects observed
- Gross pathological findings:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 1 000 other: maternal dose (mg/kg/day, actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed at highest dose tested
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- Daily oral gavage administration of the 3,9-bis[2,4-bis(1-methyl-1-phenylethyl)phenoxy]-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane(CAS: 154862-43-8) to male and female rats at dose levels of 250, 500 and 1000 mg/kg b. wt./day during pre-mating, mating, post-mating, gestation period and until post-partum day 3 did not produce test item-related adverse effects on reproduction and development. Thus, the No Observed Adverse Effect Level of the substance CAS: 154862-43-8 was found to be 1000 mg/kg b. wt./day.
Reference
Parental animals
There were non-treatment-related mortalities. There were no effects on the following parameters in parental animals: clinical signs, body weight, food consumption, organ weights, gross pathological effects, histopathological effects, reproductive performance, duration of pregnancy, pre-implantation loss, parturition index, or live birth index.
F1 animals
There were non-treatment-related mortalities. There were no effects on the following parameters in F1 animals: clinical signs, food consumption, fetal body weight changes, reduction in number of live offspring, changes in sex ratio, changes in litter size and weights, changes in postnatal survival and external malformations.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- There is one key study available and it is an OECD 421/GLP study,
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Toxicity to Reproduction (Screening)
There is one reproduction/developmental toxicity screening test in rats available.
In a reproduction/developmental toxicity screening test (OECD 421/GLP), 3,9-bis[2,4-bis(1-methyl-1-phenylethyl)phenoxy]-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane (99.3%) was administered to Wistar rats (15 animals/sex/group) by gavage in corn oil at dose levels of 0, 250, 500 or 1000 mg/kg bw/day, 7 days per week. Dosing of both the sexes was initiated 2 weeks prior to mating and continued during the mating period. After mating, the male rats were further dosed up to and including the day before scheduled sacrifice. Females were further dosed during pregnancy and up to post-partum day 3.
The concentration and homogeneity of the test item in the dose formulation was analysed using a validated HPLC method once before initiation of treatment and twice during treatment period. Dose formulations were found to be within the acceptance level of ± 15% of nominal concentration and %CV was less than 10, suggesting that the prepared formulations were homogeneously mixed.
There were non-treatment-related mortalities in parenal animals. There were no effects on the following parameters in parental animals: clinical signs, body weight, food consumption, organ weights, gross pathological effects, histopathological effects, reproductive performance, duration of pregnancy, pre-implantation loss, parturition index, or live birth index. The NOAEL was >1000 mg/kg bw//day.
There were non-treatment-related mortalities in F1 animals. There were no effects on the following parameters in F1 animals: clinical signs, food consumption, fetal body weight changes, reduction in number of live offspring, changes in sex ratio, changes in litter size and weights, changes in postnatal survival and external malformations. The NOAEL was >1000 mg/kg bw/day.
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the available information in the dossier, the conclusion for the substance 3,9-bis[2,4-bis(1-methyl-1-phenylethyl)phenoxy]-2,4,8,10-tetraoxa-3,9-diphosphaspiro[5.5]undecane (CAS No. 154862-43-8) does not need to be classified for reproductive toxicity when the criteria outlined in Annex I of 1227/2008/EC are applied.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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