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EC number: 220-482-8 | CAS number: 2781-11-5
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 05 Jun - 24 Aug 2005
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 006
- Report date:
- 2006
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- 1995
- Deviations:
- yes
- Remarks:
- gross pathological findings were not examined in the F1 generation
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Diethyl bis(2-hydroxyethyl)aminomethylphosphonate
- EC Number:
- 220-482-8
- EC Name:
- Diethyl bis(2-hydroxyethyl)aminomethylphosphonate
- Cas Number:
- 2781-11-5
- Molecular formula:
- C9H22NO5P
- IUPAC Name:
- diethyl {[bis(2-hydroxyethyl)amino]methyl}phosphonate
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- - Date of receipt: 29 Apr 2005
- Color: amber
- Form: liquid
- Storage conditions: room temperature (approx. 22 ± 3°C), protected from light
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Taconic Farms, Germantown, USA
- Females nulliparous and non-pregnant: yes
- Age at study initiation: (P) x 8 wks
- Weight at study initiation: (P) Males: 190-214 g; Females: 161-173 g
- Housing: individually in stainless steel cages; one male and one female in polycarbonate shoebox with corncob bedding during mating period.
- Diet: Harlan Teklad Certified Rodent Diet 8728C ad libitum
- Water: tap water from the city of Chicago ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 05 Jun 2005 To: 24 Aug 2005
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- deionized
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
DIET PREPARATION
- Rate of preparation of diet: every week
- Mixing appropriate amounts with: water
- Storage temperature of food: room temperature (approx. 22 ± 3°C)
VEHICLE
- Concentration in vehicle: 10, 50 and 150 mg/mL
- Amount of vehicle: 5 mL/kg bw - Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: up to 2 weeks
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged: individually shoebox cage with corncob bedding - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples of the dosing formulations taken from the 1st, 2nd and 7th week preparations were analyzed for homogeneity via HPLC-UV prior to using. The analytically determined concentrations were within 10% of the target concentrations.
- Duration of treatment / exposure:
- (P) Males: 2 weeks before mating, 1 week during mating, 2 weeks after mating (minimum of 35 days)
(P) Females: 2 weeks before mating, 1 week during mating, during gestation and lactation until post-partum day 4 (minimum of 46 days) - Frequency of treatment:
- 7 days/week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 750 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 12 P males and 12 P females per tested concentration and per control
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Doses were selected by the sponsor based on the results of previous toxicity studies with the test material.
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: 1 day prior to treatment initiation and weekly thereafter
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as gfood/kg body weight/day: No
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
- Oestrous cyclicity (parental animals):
- The stage of the estrous cycle was determined with daily vaginal smears taken during mating period until evidence for mating was found.
- Sperm parameters (parental animals):
- Parameters examined in P male parental generations:
testis weight and epididymis weight, stages of spermatogenesis and interstitial testicular cell structure - Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births
GROSS EXAMINATION OF DEAD PUPS:
yes, for external abnormalities; possible cause of death was not determined for pups born or found dead. - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals, including those found dead or euthanized moribund
- Maternal animals: All surviving animals, including those found dead or euthanized moribund
GROSS NECROPSY
- Gross necropsy consisted of examination of the external body surface, all orifices, the cranial, thoracic, and peritoneal cavities and their contents.
HISTOPATHOLOGY / ORGAN WEIGHTS
- The tissues of livers, ovaries, testes and epididymides were prepared for microscopic examination and weighed, respectively. - Postmortem examinations (offspring):
- The F1 animals were not subjected to postmortem examinations.
- Statistics:
- Calculation of means and standard deviations using Microsoft Excel; Systat 10 used for remaining statistical analysis. Analysis of data for homogeneity of variance using Levene's test. In case of homogeneous data, the data were further analyzed by one-way analysis of variance (ANOVA); in case of non-homogeneous data, Dunnett's test was performed for post-hoc comparisons. Mating and absolute pup-survival were analyzed using the Chi-Square test.
- Reproductive indices:
- Successful Mating: (# Successful Parturation / # Selected for Littering) x 100
% Pre-implantation loss = [(Total Corpora Lutea - Total Corpora Implants) / Total Corpora Lutea] x 100
% Post-implantation loss = [(Total Implants - Total Born) / Total Implants] x 100 - Offspring viability indices:
- % alive on day 0 = [(Total number of pups born - number of stillborn fetuses) / Total number of pups born] x 100
% alive on day 4 = (number alive on day 4 / number alive on day 0) x 100
% surviving = (number alive on day 4 / number alive on day 0) x 100
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- All signs observed (i.e. alopecia, red material around nose/eyes, forelimbs/gead scab, and ventral mass) were sporadically distributed among the groups and low in incidence.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One control female (animal number 62) died during the first week of the study due to gavage trauma.
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Body weight and body weight gain were similar across all groups with no observed treatment-related trends.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Food consumption was not affected by treatment.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Endocrine findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Histopathological findings (i.e. degeneration of germinal epithelium in the testes and interstitial infiltration with mixed cells in the epididymides) were considered incidental and non-treatment related.
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- reproductive
- Effect level:
- >= 750 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed up to highest dose tested
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (P0)
- Key result
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Anogenital distance (AGD):
- not examined
- Nipple retention in male pups:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 750 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: no adverse effects were observed up to the highest concentration
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- Based on these findings, the no-observed-adverse-effect level (NOAEL) for systemic and reproductive toxicity is equal to or greater than the highest dose tested 750 mg/kg bw/day.
- Executive summary:
Test Item was formulated in deionized water (vehicle) and was administered as a solution by oral gavage at dose levels of 0 (vehicle control), 50, 250 or 750 mg/kg bw/day to 12 Sprague Dawley rats/sex/group for the assessment of reproductive and developmental toxicity. Doses were administered at a constant volume of 5 mL/kg bw for 2 weeks prior to mating, during the approximately 1-week mating period, through gestation and lactation until sacrifice, for a total of 5 weeks of dosing for males and approximately 7 weeks for females. Parental food consumption, body weights, body weight gain, reproductive performance, organ weights and histopathology were evaluated during the study, along with offspring body weight and survival.
No treatment-related clinical signs or deaths occurred during the study. Parental body weight, body weight gain and food consumption were unaffected by treatment.
No statistically significant differences in mean corpora lutea, implantation sites, litter size, total pups born or pups born alive on postnatal days 0 were detected among the groups. Pup survival was unaffected by treatment on postnatal day 0 and 4. Offspring body weight and growth were similar across all groups and unaffected by treatment.
Parental reproductive organ weights (ovaries, testes or epididymides) failed to reveal any treatment-related effect. Male liver weights and liver-to-body weight ratios were increased in a dose-related manner; however, statistical significance was not achieved. No evidence of histological changes was observed in the ovaries, testes or epididymides.
Based on these findings, the no-observed-adverse-effect level (NOAEL) for systemic and reproductive toxicity is equal to or greater than the highest dose tested 750 mg/kg bw/day.
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