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EC number: 418-570-8 | CAS number: 25383-07-7
- 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
Acute Toxicity: oral
Administrative data
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- July 23, 1994 - July 29, 1994
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.1 (Acute Toxicity (Oral))
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Deviations:
- no
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
Test material
- Reference substance name:
- (R)-α-phenylethylammonium (-)-(1R, 2S)-(1,2-epoxypropyl)phosphonate monohydrate
- EC Number:
- 418-570-8
- EC Name:
- (R)-α-phenylethylammonium (-)-(1R, 2S)-(1,2-epoxypropyl)phosphonate monohydrate
- Cas Number:
- 25383-07-7
- Molecular formula:
- C11H20NO5P
- IUPAC Name:
- (R)-α-phenylethylammonium (-)-(1R, 2S)-(1,2-epoxypropyl)phosphonate monohydrate
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Name of test material (as cited in study report): Fosfomycin PEA salt
- Physical state: white crystalline powder
- Lot/batch No.: 4177
- Expiration date of the lot/batch: at least 3 years from the manufacturing date
- Stability under test conditions: at least 3 years
- Storage condition of test material: plastic bag in a cartboard box, at room temperature protected from the light.
- Other: manufacturing date: June 10, 1994
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Italia S.p.A.
- Age at study initiation: 7/9 weeks
- Weight at study initiation: Males: 225-250 g. Females: 200-225 g
- Fasting period before study: 16 hours
- Housing: 5 animals/sex/cage in T11C air-conditioned room in grill cages 40.5x38.5x18h cm with stainless feeder.
- Diet (e.g. ad libitum): Ad libitum (GLP 4RF21 top certificate pellet diet)
- Water (e.g. ad libitum): Ad libitum (from the municipal water main system, filtered).
- Acclimation period: Five days before the start of the test
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 ºC
- Humidity (%): 55 ± 10 %
- Air changes (per hr): 20 per hour (filtered on HEPA 99.97 %)
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light (7 a.m - 7 p.m)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: Methocel (methylcellulosae aqueous solution)
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: 100 mg/ml
MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg - Doses:
- 2000 mg/kg bw
- No. of animals per sex per dose:
- 5
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs and mortality: at 30 minutes, 2, 4 and 6 hours on the first day after the administration (day 1) and then twice a day up to termination of the observation period.
Weighing: twice pre-trial (at randomization and on day 1 just before administration) and on days 3, 8 and 14.
- Necropsy of survivors performed: Yes. All surviving animals (fasted overnight) were killed by excision of the femoral arteries, after i.p. overdosage anesthesia with 5% sodium pentobarbital.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Clinical signs and behaviour, body weight and gross pathology examinations.
Results and discussion
Effect levels
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No animals died during the observation period.
- Clinical signs:
- Signs involving the CNS (hypoactivity, muscular tremors, palpebral closure and hypothermia), the respiratory apparatus (shallow breathing) and piloerection, hunched posture and salivation were clinically observed in the treated rats starting from 30 minutes - 4 hours and lasting up to 6-24 hours after the test article administration. Sporadic cases of ataxia, reddish nasal discharge and chromodacryorrhea were also observed in some animals during the first days of the study. Recovery of all treated rats was achieved within 24 (females) - 48 hours (males) of treatment.
- Body weight:
- Low body weight gain was observed in some animals only at the day 3 weighing. Body weight gain returned to normal at the subsequent weighings.
- Gross pathology:
- No appreciable macroscopic findings were evident in any treated rat.
Any other information on results incl. tables
Table 1. Clinical signs frequency (cumulative)
Clinical signs |
No. of rats affected |
Signs observed (time) |
|
From* |
To** |
||
Hypoactivity |
10 |
30 m |
6 h |
Ataxia |
2 |
2 h |
6 h |
Reddish nasal discharge |
2 |
2 d |
- |
Shallow breathing |
3 |
2 h |
2 d |
Piloerection |
10 |
30 m |
2 d |
Hunched posture |
10 |
30 m |
2 d |
Muscular tremors |
6 |
30 m |
6 h |
Salivation |
6 |
30 m |
6 h |
Chromodacryorrhea |
1 |
2 d |
- |
Palpebral closure |
4 |
4 h |
6 h |
Hypothermia |
3 |
2 h |
2 d |
Recovery |
10 |
2 d |
3 d |
* first observation in one or more animals; ** last observation in one or more animals.
(day of treatment = day 1)
Table 2. Body weight (g). Dose: 2000 mg/kg.
Day |
1 M |
2 M |
3 M |
4 M |
5 M |
6F |
7F |
8F |
9F |
10F |
Pre-trial |
269 |
260 |
269 |
274 |
267 |
242 |
228 |
224 |
228 |
236 |
1* |
247 |
235 |
248 |
250 |
238 |
220 |
209 |
209 |
210 |
214 |
3 |
258 |
251 |
269 |
260 |
249 |
226 |
209 |
214 |
215 |
224 |
8 |
298 |
287 |
305 |
285 |
301 |
248 |
229 |
236 |
261 |
248 |
14 |
362 |
344 |
352 |
353 |
344 |
263 |
252 |
253 |
281 |
270 |
Table 3. Gross pathology examination.
Dose (mg/kg) |
Animals |
Macroscopic findings |
2000 |
Males No. 1-5 |
No appreciable macroscopic findings |
|
Females No. 6-10 |
No appreciable macroscopic findings |
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Remarks:
- EU criteria.
- Conclusions:
- The oral LD50 of the test article in rats was higher than 2000 mg/kg bw.
- Executive summary:
A toxicity study in Sprague Dawley Crl:CD (SD) rats (5 males and 5 females) with a single oral administration of the test article Fosfomycin PEA salt at the dosage of 2000 mg/kg bw (limit dose) was performed in accordance with EU Method B.1 and OECD Guideline 401. The test article was administered as a suspension in 0.4% methylcelllulosae aqueous solution at the constant volume of 20 ml/kg. All rats were treated after a 16 hour fasting period. The day of treatment was considered day 1 of the study. The animals were weighed twice before treatment (at randomization and on day 1 just before treatment) and on days 3, 8 and 14. They were clinically observed for 14 days following the treatment. On day 15 all treated rats were killed by excision of the femoral arteries, after i.p. overdosage anesthesia with 5% sodium pentobarbital and they were submitted to a thorough autopsy.
No animals died during the observation period.
The main clinical signs observed were: hypoactivity, muscular tremors, palpebral closure and hypothermia), the respiratory apparatus (shallow breathing) and piloerection, hunched posture starting from 30 minutes - 4 hours and lasting up to 6-24 hours after the test article administration. Sporadic cases of ataxia, reddish nasal discharge and chromodacryorrhea were also observed in some animals during the first days of the study. Recovery of all treated rats was achieved within 24 (females) - 48 hours (males) of treatment.
Low body weight gain was observed in some animals only at the day 3 weighing. Body weight gain returned to normal at the subsequent weighings. No appreciable macroscopic findings were evident in any treated rat.
In conclusion, the oral LD50 of the test article in rats was higher than 2000 mg/kg bw and transient clinical signs involving the CNS and the respiratory apparatus were the main findings.
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