Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 251-908-0 | CAS number: 34274-28-7
- 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:
- No data. Dates of treatment were 27.12.1978 to 19.01.1979
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Remarks:
- The study is a read across from ATMP (CAS 6419-19-8).
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 979
- Report date:
- 1979
Materials and methods
Test guideline
- Guideline:
- other: FDA "Guidelines for reproductive studies for evaluation of drugs for human use", segment II (teratological study)
- Deviations:
- not specified
- Remarks:
- Treatment on GD 6 - 15; no record of gravid uterine weight; number corpora lutea not recorded; no analytical confirmation of exposure levels.
- Principles of method if other than guideline:
- Study was used to assess the teratogenic and/or embryotoxic potential of the test substance.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- [nitrilotris(methylene)]trisphosphonic acid, sodium salt
- EC Number:
- 243-900-0
- EC Name:
- [nitrilotris(methylene)]trisphosphonic acid, sodium salt
- Cas Number:
- 20592-85-2
- Molecular formula:
- General formula C3H12NO9P3.xNa where x=3-5 ATMP-3Na C3H9NNa3O9P3 ATMP-4Na C3H8NNa4O9P3 ATMP-5Na C3H7NNa5O9P3
- IUPAC Name:
- Sodium salt of [nitrilotris(methylene)]trisphosphonic acid (3-5Na:1)
- Test material form:
- liquid
1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- 72 d at mating
Weight: approx. 240 - 250 Number: 24 / dose Supplier: Charles River, Wilmington, Mass. Individually housed, food (Purina Certified Rodent Chow 5002) and water available ad libitum.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- ADMINISTRATION / EXPOSURE GD 6-15 Test substance mixed with water, administered at 10 mg/kg/d. Volume adjusted based on most recent body weight data. Prepared daily.
- Analytical verification of doses or concentrations:
- no
- Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1:2
- Length of cohabitation: Overnight
- Further matings after two unsuccessful attempts: No data
- Verification of same strain and source of both sexes: No data
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy. - Duration of treatment / exposure:
- GD 6 - 15
- Frequency of treatment:
- daily
- Duration of test:
- 16 days
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day
- Remarks:
- measured as the active acid
- Dose / conc.:
- 500 mg/kg bw/day
- Remarks:
- measured as the active acid
- Dose / conc.:
- 1 000 mg/kg bw/day
- Remarks:
- measured as the active acid
- No. of animals per sex per dose:
- 24 mated females/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Sex: female
Duration of test: 21 d
Examinations
- Maternal examinations:
- Clinical observations performed and frequency: - gross signs, twice daily - detailed physical examination of GD 0, 6, 10, 15, 20 and 21 (pre-necropsy) Parent: - bwt: GD 0, 6 -15, 21
- Organs examined at necropsy Dams sacrificed on GD21 by lethal exposure to diethyl ether.
Parent: - complete post-mortem examination - uterus: live / dead foetuses, late / early resorptions, implantation sites - ovaries: corporea lutea per ovary - Fetal examinations:
- Fetal: - crown-rump distance - sex (anogenital distance) - external malformations - approx. 50% of foetuses subject to gross dissection and visceral examination followed by processing / staining (Alizarin red) for skeletal abnormalities / variations - remainder subject to Wilson serial sectioning for neural / visceral defects (10X or 20X magnification) after fixing in Bouin's solution
- Statistics:
- Chi squared or F-test and Student's T-test. T-tests modified using Cochran's approximation when variances differed significantly. Live foetuses, resorptions, implantations and corpora lutea compared using one-tailed T-test.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No clinical signs in any dose groups were found.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One female in the 100 mg/kg bw/day dose group was concluded to be in moribund condition and was sacrificed on GD6 (first day of treatment).
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- No significant differences were found in maternal body weight gain between groups. The body weight gain GD6-15: 50/49/50/44 - 12% (non-significant) reduction in body weight gain at 1000 mg/kg bw/d on GD6-15. Individual body weight gain for dam 822 (high dose) on GD6-15 = 22 g; mean gain for controls = 50 g; mean gain for high dose group = 44 g. Body weight gain for this dam on GD 0-6 (preceding treatment) and on GD 15-21 (post-treatment) was similar or greater than mean bdoy weight gain for control and high dose group.
- Food consumption and compound intake (if feeding study):
- not examined
- 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:
- not examined
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were observed in any of the dose groups.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- effects observed, non-treatment-related
- Description (incidence and severity):
- A statistical significant 7.5 % increase in implantation efficiency at 100 mg/kg bw/day was observed. However, this was considered unrelated to the test substance by authors as the implantation (14.5/14.7/14.0/13.7) and implantation efficiency (84.3%/91.8%/84.0%/81.2%) was comparable.
- Total litter losses by resorption:
- no effects observed
- Description (incidence and severity):
- Mean number of resorptions were 0.2/0.8/0.5/0.8 which were all within historical control range data, There was an increase although not statistical significant increase in dams with 2 or more resorptions in treated groups (0%/22.7%/8.3%/20.8%), However, this was also within historical control range and therefore, considered to not be test substance treatment-related effects.
- Early or late resorptions:
- not specified
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- No dead foetuses were observed in any of the dose groups.
- Changes in number of pregnant:
- no effects observed
- Description (incidence and severity):
- The pregnancy rate was comparable between all dose groups (100% in control, mid and high dose groups, 95.6% at 100 mg/kg bw/d).
- Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The mean number of corpora lutea were 17.2/16.0/16.7/16.8. The 100 mg/kg bw/day dose group had a 7% decrease in corpora lutea. However, this was considered by the authors to be unrelated to the treatment
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 500 mg/kg bw/day
- Based on:
- act. ingr.
- Remarks:
- active acid
- Basis for effect level:
- other: Effects on body weigh gain.
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- not specified
- Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- Sex: males/litter 6.9/7.0/6.6/6.0; females 7.4/6.9/7.0/6.9 (no significant effect). Sex ratio (m:f): 92.4%/102.0%/94.6%/87.3% (no significant effect)
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- The body weight for males were 5.54/5.43/5.71/5.49 and for females 5.25/5.17/5.34/5.16 which did not indicate any significant effect.
- Anogenital distance of all rodent fetuses:
- not examined
- Changes in postnatal survival:
- not examined
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- In the 1000 mg/kg bw/day dose group, one female had 6 foetuses (from a total litter of 16) with a syndrome of defects that included: flexed forepaws, shortened and thickened torso, abdominal distension and exaggerated forward flexure of the head (see maternal body weight, above). No other animals, including the other animals in the 1000 mg/kg bw/day dose group, had any external malformations and thereby, this effect were considered to be incidental and not related to treatment of the test substance.
- Description (incidence and severity):
- Total of foetuses examined: 177/158/169/159 - per foetus: 4.0%/1.9%/3.0%/1.3% (no significant effect) - per litter: 20.8%/13.6%/20.8%/8.7% (no significant effect). In the control dose group, angulated ribs, cervical rib and wavy rib were observed. In the 100 mg/kg bw/day dose group, angulated rib, cervical rib as well as angulated and wavy rib were observed. In the 500 mg/kg bw/day dose group. cervical rib, angulated and wavy rib as well as 7 lumbar vertebra were observed. In the 1000 mg/kg bw/day dose group, 5 lumbar vertebra and fused sternebrae were observed. There was no significant variation in the ossification: fetuses 80.2%/83.5%/79.3%/84.3%; litters 95.8%/100.0%/100.0%/100.0%.
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Total foetuses examined: 162/147/156/150 - per fetus: 4.3%/8.2%/4.5%/4.0% (no significant effect) - per litter: 16.7%/40.9%/29.2%/20.8% (no significant effect). In the control dose group, distended renal pelvis, renal pelvis, ureter and bladder malformations were observed. In the 100 mg/kg bw/day dose group, a similar incidence in the control dose group as well as a fold in retina. In the 500 mg/kg bw/day dose group, a similar incidence as in the control dose group as well as ectopic kidney. In the 1000 mg/kg bw/day dose group, a similar incidence as in the control dose group as well as fold in retina, anophthalmia, malrotation of heart occurring in two foetuses from the same litter which had an altered maternal body weight and observed external malformations.
The incidence of visceral malformations per fetus were: 0.6%/1.3%/0.6%/1.9% (no significant effect) - per litter: 4.2%/9.1%/4.2%/12.% (no significant effect). In the control dose group, distended ureter was observed. In the 100 mg/kg bw/day, a distended ureter +/- renal pelvis occurred. In the 500 mg/kg bw/day dose group, a similar incidence occurred as in the control dose group. In the 1000 mg/kg bw/day, a similar incidence occurred as in the control dose group as well as malpositioned testis were observed. - Other effects:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Crown-rump length: males 4.2/4.2/4.3 (P<0.01)/4.2; females 4.1/4.1/4.2 (P<0.01)/4.1. There was an increase at 500 mg/kg bw/day, however, this was not considered be of biological insignificance by authors.
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Effect levels (fetuses)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- act. ingr.
- Remarks:
- active acid
- Sex:
- male/female
- Basis for effect level:
- other: No teratogenic effects observed.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- act. ingr.
- Remarks:
- active acid
- Sex:
- male/female
- Basis for effect level:
- other: No fetotoxic effects observed.
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- In a well-documented pre-GLP teratology study (FDA segment II teratological study; reliability score 2) ATMP-H (aqueous solution containing 22.4% w/w active acid) was not embryotoxic or teratogenic when administered to rats at 100 or 500 mg active acid/kg bw/day (measured as the active acid) by gavage on GD6-15. At 1000 mg/kg bw/d, six fetuses from a single litter showed common multiple malformations in presence of a 50% decrease in individual maternal body weight gain (possibly indicative of concurrent maternal toxicity); all other high dose fetuses were normal. The clear absence of any comparable effect in other high dose litters and lack of dose-response indicates that 1000 mg active acid/kg bwt/d was the no-effect level for embryotoxicity and fetotoxicity. The maternal NOAEL was 500 mg active acid/kg bw/day.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.