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EC number: 278-636-5 | CAS number: 77182-82-2
- 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
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Oct 1983 - May 1985
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 985
- Report date:
- 1985
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Version / remarks:
- May 1981
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)
- Version / remarks:
- Nov 1982
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Ammonium 2-amino-4-(hydroxymethylphosphinyl)butyrate
- EC Number:
- 278-636-5
- EC Name:
- Ammonium 2-amino-4-(hydroxymethylphosphinyl)butyrate
- Cas Number:
- 77182-82-2
- Molecular formula:
- C5H12NO4P.H3N
- IUPAC Name:
- ammonium 2-amino-4-[hydroxy(methyl)phosphoryl]butanoate
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Remarks:
- Hoe: WISKf (SPF71)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hoechst AG, Pharma Forschung Toxikologie, Kastengrund, Germany
- Age at study initiation: about 8-10 weeks
- Weight at study initiation: males: 143-154 g; females: 144-154 g
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 8/9 days
DETAILS OF FOOD AND WATER QUALITY:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 16
- Photoperiod (hrs dark / hrs light): 12/12 (illumination: 7 am to 7 pm)
IN-LIFE DATES: From: 17.10.1983 To: 08/09.12.1983
Administration / exposure
- Type of coverage:
- occlusive
- Vehicle:
- other: physiological saline
- Details on exposure:
- TEST SITE
- Area of exposure: nape (shaved)
- % coverage: 10
- Type of wrap if used: bandage (aluminium foil, Fixomull-Strech adhesive plaster)
- Time intervals for shavings or clipplings: at least once weekly
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, washed
- Time after start of exposure: Exposure for 6 h. After removal of bandage, treated skin was washed.
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.3 ml/kg bw
- Concentration (if solution): 7.5, 22.5, 75.0% solution (w/v)
- Constant volume or concentration used: yes
- For solids, paste formed: no, solution in deionized water
VEHICLE
- Justification for use and choice of vehicle (if other than water): deionized water
USE OF RESTRAINERS FOR PREVENTING INGESTION: not specified - Duration of treatment / exposure:
- 30 days (21 applications)
- Frequency of treatment:
- Monday-Friday, 6 h/d
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day
- Dose / conc.:
- 300 mg/kg bw/day
- Dose / conc.:
- 1 000 mg/kg bw/day
- No. of animals per sex per dose:
- 6 (5 for recovery groups; control and high dose)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
- Rationale for animal assignment (if not random): random
- Fasting period before blood sampling for clinical biochemistry:
- Rationale for selecting satellite groups:
- Post-exposure recovery period in satellite groups: 14 days
- Section schedule rationale (if not random):
- Other: - Positive control:
- not included
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Daily
BODY WEIGHT: Yes
- Time schedule for examinations: Twice weekly
FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Time schedule: Twice weekly
WATER CONSUMPTION: Yes
- Time schedule for examinations: Once weekly
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At the end of the study
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: All animals
- Parameters checked: hemoglobin, erythrocytes, leucocytes, hematocrit, reticulocytes, differential blood count*, thrombocytes, coagulation time, erythrocyte sedimentation rate, thromboplastin time, activated partial thromboplastin time, methemoglobin*. MCV, MCH, and MCHC were also calculated. (* no evaluation for 100 and 300 mg/kg bw/day groups, since the findings for 1000 mg/kg bw/day were normal)
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At the end of the study
- Animals fasted: No
- How many animals: All animals
- Parameters checked: sodium, potassium, inorg. phosphorus, uric acid, total bilirubin, direct bilirubin, creatinine, serum glucose, urea nitrogen, calcium, chloride, SGOT, SGPT, AP, LDH, cholesterol, total lipids, total protein, serum electrophoresis
- In view of the results at the end of the treatment period, the only parameters examined at the end of the recovery period were chloride and uric acid in the males and sodium, potassium and chloride in the females.
URINALYSIS: Yes
- Time schedule for collection of urine: At the end of the study (In the night from Day 28 to 29)
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters checked: Appearance, color, protein, glucose, hemoglobin, bilirubin, pH, sediment. No urinalysis was carried out at the end of the recovery period, since there were no substance-related changes
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- Autopsy included skin, orifices, eyes, teeth, oral mucosa, and internal organs
- Organs weighed: heart, lungs, liver, kidneys, spleen, brain, testes (without epididymes)/ovaries, adrenals, pituitary, thyroid
HISTOPATHOLOGY: Yes
heart, urinary, bladder, pancreas, lungs, testes, adrenals, liver, epididymides, thymus, kidneys, prostate, pituitary, spleen, seminal vesicles, brain, stomach, ovaries, eye with optic nerve, jejunum, uterus, bone marrow (femoral), colon, thyroid, treated skin areas, untreated skin areas - Statistics:
- Dunnett's test, Sidak test, Nemenyi/Dunnett, Nemenyi/Sidak
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- - 1000 mg/kg bw/day: 4 males and 2 females showed piloerection. One male animal refused its food almost entirely from the beginning of the
second week of treatment and had to be removed from the study in a cachectic condition on day 16; encrusted blood was also observed around the eyes and the mouth/nose of this animal.
- 300 mg/kg bw/day: one male animal showed notably aggressive behaviour, squatting position, pilo-erection and convulsive jumping and rolling spasms at the end of the treatment period. - Dermal irritation:
- effects observed, treatment-related
- Description (incidence and severity):
- On days 5 and 6 of the study, slight signs of irritation appeared on the treated skin areas of the females. During the further course of the study no
signs of dermal irritation were observed in either the females or the males. - Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- - 1000 mg/kg bw/day: One male was humanely killed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- - 300 mg/kg bw/day: decreased APTT in males, increased APTT in females. Decreased leucocytes in males
Since these changes were not dose-related and occurred only to a minimal extent and without further toxicological correlates, they must be considered as non-substance-related and of no toxicological relevance. - Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- - 1000 mg/kg bw/day: In males, a slight increase in uric acid and potassium; Decreases in sodium in females and chloride in both sexes
- 300 mg/kg bw/day: In males, a slight increase in uric acid and alpha3 globulin; decrease in sodium in females
- 100 mg/kg bw/day: Increase in gamma1 globulin in females
Effects cannot be considered as toxicologically relevant (independent of dose level and only to a minimum extent). Uric acid levels were still within range of normal biological variation and were thus considered not toxicologically relevant. - Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- effects observed, treatment-related
- Description (incidence and severity):
- - 1000 mg/kg bw/day: 4 males and 2 females showed either timid or aggressive behavior, increased motor excitation (especially followign tactile stimuli), or squatting position
- 300 mg/kg bw/day: one male showed notably aggressive behavior, squatting position, convulsive jumping, and rolling spasms - Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- clinical signs
- Remarks on result:
- other: NOEL comparable to NOAEL
Target system / organ toxicity
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 300 mg/kg bw/day
- System:
- central nervous system
- Organ:
- brain
- Treatment related:
- yes
- Dose response relationship:
- yes
Any other information on results incl. tables
Table 1: Clinical findings
Dose group (mg/kg bw/day) |
Sex |
Day of treatment |
Symptoms |
control |
Male |
1-30 |
No symptoms |
Female |
1-30 |
No symptoms* |
|
100 |
Male |
1-30 |
No symptoms |
Female |
1-30 |
No symptoms |
|
300 |
Male |
|
|
Animal No 19 |
10-15 10-19 |
aggressive behavior easily startled |
|
Animal No 23 |
24-30 27-30 |
Aggressive behavior, ‘kangaroo’ position, piloerection Convulsive jumpings |
|
Female |
1-30 |
No symptoms |
|
1000 |
Male |
|
|
Animal No 24 |
7-16 8-16 13-16 |
Right upper rodent tooth broken, ‘kangaroo’ position, crusted eyes, blood crusted nose Narrowed eye opening Piloerection, hyporeflexia, decreased respiratory rate, abdominal position |
|
Animal No 26 |
16-23 20-23 23 |
Aggressive behavior Easily startled piloerection |
|
Animal No 27 |
10-15 10-26 |
Aggressive behavior Easily startled |
|
Animal No 28 |
20-26 |
Lesion on the left foreleg |
|
Animal No 30 |
7-12 7-26 |
Aggressive behavior Hyperactivity following tactile stimulus |
|
Animal No 33 |
10-16 10-22 |
Aggressive behavior Easily startled |
|
Female |
|
|
|
Animal No 64 |
6-15 |
Hyperactivity following tactile stimulus |
|
Animal No 68 |
12-19 12-32 |
‘kangaroo’ position piloerection |
* Four females showed lesions; however, they were due to removing the occlusive bandage by test animal
Applicant's summary and conclusion
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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