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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 243-900-0 | CAS number: 20592-85-2
- 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
Carcinogenicity
Administrative data
Description of key information
There are no data for ATMP-xNa (CAS 20592-85-2, EC No., 243-900-0), therefore data were read-across from ATMP-H (CAS 6419-19-8; EC 229-146-5).
In a well-conducted key chronic toxicity/carcinogenicity study, ATMP-H (powder, 100% active acid) was administered via the diet to Long-Evans rats at dose levels of 50, 150 or 500 mg active acid/kg bw/day for 24 months. The NOAEL for carcinogenicity and general toxicity was at least 500 mg active acid/kg bw/day (BioDynamics Inc., 1979c, Reliability 2).
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 04.12.1975 to 03.12.1979
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- Version / remarks:
- Study conducted prior to adoption of OECD test guideline.
- Deviations:
- yes
- Remarks:
- No satellite groups, limited measurements of blood and clinical chemistry parameters.
- GLP compliance:
- no
- Remarks:
- pre-GLP
- Species:
- rat
- Strain:
- Long-Evans
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Blue Spruce Farms, Altamont, New York.
- Age at study initiation: 6-7 weeks
- Weight at study initiation: Mean 212.6 g (males) and 149.0 g (females)
- Fasting period before study: Not specified
- Housing: Individually in elevated stainless steel cages.
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 18 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Monitored but no data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light
IN-LIFE DATES: From: 17.11.1976 To: 30.11.1978 - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- DIET PREPARATION
- Rate of preparation of diet: Weekly
- Mixing appropriate amounts with: Standard laboratory diet.
- Storage temperature of food: No data - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- 50 gram samples of the control feed and each dietary level were taken weekly and shipped to the sponsor. No further details.
- Duration of treatment / exposure:
- 24 months
- Frequency of treatment:
- Continuous
- Post exposure period:
- None.
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Remarks:
- active acid
- Dose / conc.:
- 150 mg/kg bw/day (actual dose received)
- Remarks:
- active acid
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Remarks:
- active acid
- No. of animals per sex per dose:
- 70
- Control animals:
- yes, plain diet
- Details on study design:
- Post-exposure period: None
Satellite groups: None - Positive control:
- None
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily for the first two months and then twice daily until termination.
- Cage side observations: Mortality, gross signs of toxicology or pharmacologic effects.
Interim necropsies were performed on 10/sex/group after 6 and 12 months, then on all surviving animals after 24 months. Animals that died spontaneously or were killed in a moribund condition were also examined.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly, for signs of local or systemic toxicity, pharmacologic effects and palpation for tissue masses.
BODY WEIGHT: Yes
- Time schedule for examinations: Twice pre-test, weekly through to week 13 of treatment, every two weeks for weeks 14 to 26, then monthly, and finally at termination.
FOOD CONSUMPTION AND COMPOUND INTAKE: pretest, weekly up to week 13, every other week for weeks 14 to 26 and then monthly.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION AND COMPOUND INTAKE: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Pretest, then 3, 6, 12, 18 and 24 months.
- Dose groups that were examined: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At 3, 6, 12, 18 and 24 months.
- Anaesthetic used for blood collection: Yes, ether.
- Animals fasted: Yes, overnight.
- How many animals: 6/sex from control and high dose groups.
- Parameters checked in table [No.1] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At 3, 6, 12, 18 and 24 months.
- Animals fasted: Yes, overnight
- How many animals: 6/sex from control and high dose groups.
- Parameters checked in table [No. 1] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: 6, 12 and 24 months all groups 6/sex; 3 months: 6/group (males) and 6/control and high dose groups (females); 18 months: 6/sex for control and high dose groups.
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined.
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 2)
HISTOPATHOLOGY: Yes (see table 2) - Other examinations:
- None
- Statistics:
- Body weight, food consumption, haematology and clinical chemistry parameters, organ weights, organ/body weight ratios and organ/brain weight ratios were analysed. Mean values of all dose groups were compared to control at each time interval. Haematology and clinical chemistry: intergroup comparison v control by F-test and Student's t-test (using t-test modification if variances differed). Body weight, food consumption, organ weights and ratios by Dunnett's t-test.
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no physical observations that were attributed to the administration of the test substance.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- Mortality data did not reveal any treatment-related effect. Males (per 70): 18 (controls), 22 (low), 21 (medium) and 18 (high) died. Females (per 70): 23 (controls), 24 (low), 19 (medium) and 19 (high) died during study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean body weight values for the high dose males were slightly reduced (5-10%) from week 16 to 87 resulting in slight reduction in terminal body weight, however, this was not statistically significant. Values for the low and mid dose groups were comparable to the controls.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Mean food consumption values for the high dose males were generally comparable to or greater than those of the control group (3-17%) during most weeks. Values for the low and mid dose groups were comparable to the controls.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related effects.
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were observed.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were observed.
- Endocrine findings:
- not examined
- Urinalysis findings:
- no effects observed
- Description (incidence and severity):
- No treatment-related effects were observed.
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Changes were observed in the highest dose group only. No other groups were affected at any sample time. Males: 15% reduction in absolute spleen weight at 24 months; 14% reduction in absolute and relative liver weight at 24 months; 23% increase in relative testes weight at 12 months, 14% increase in relative kidney weight at 12 months, 14% decrease in absolute liver weight at 6 months. Females: 13% decrease in absolute kidney weight at 12 months; 8% decrease in relative liver weight at 6 months. These changes were not considered adverse.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no gross lesions attributable to treatment.
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- No treatment-related findings.
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- No treatment-related findings were observed. Isolated miscellaneous tumours were present in all dose groups, however, there is no evidence that this would be a treatment-related effect.
- Other effects:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 500 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Remarks:
- active acid
- Sex:
- male/female
- Basis for effect level:
- other: No neoplastic findings.
- Critical effects observed:
- no
- Conclusions:
- In a carcinogenicity study (reliability score 2), conducted in a protocol similar to OECD Test Guideline 453 but pre-GLP, ATMP-H (powder, 100% active acid) was administered via the diet to Long-Evans rats at dose levels of 50, 150 or 500 mg active acid/kg bw/day for 24 months. The NOAEL for carcinogenicity and general toxicity in male and females was ≥ 500 mg active acid/kg bw/day.
Reference
Table 3 Summary of number of in-lfe masses observed at necropsy.
Group (mg/kg bw/day) | I (0) | II (50) | III (150) | IV (500) | ||||
Number | % | Number | % | Number | % | Number | % | |
Males | 20/70 | 28.6 | 20/70 | 28.6 | 21/70 | 30 | 15/70 | 21.4 |
Females | 22/70 | 31.4 | 23/70 | 32.9 | 17/70 | 24.3 | 20/70 | 28.6 |
Table 4 Summary of observed tumours.
Time of examination | Type of neoplastic change | |||
Group I | Group II | Group III | Group IV | |
6 months | None | None | None | None |
12 months | Adrenal pharochonacytoma (1f) |
Pituitary |
Uterine polyp (1f) |
Pituitary |
24 months* | Osteosarcoma axilla (1m) |
*pituitary and mammary tumours common.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 500 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Based on the available read-across data from the ATMP-H, no classification is required for carcinogenicity for ATMP-xNa according to Regulation (EC) No 1272/2008.
Additional information
There are no data for ATMP-xNa, therefore data were read-across from ATMP-H. See attachment to IUCLID Section 13 for justification of read-across.
In the key chronic toxicity and carcinogenicity study, conducted in a similar manner to OECD Test Guideline 453 but pre-GLP, ATMP-H (powder, 100% active acid) was administered via the diet to Long-Evans rats (70/sex/dose) at dose levels of 50, 150 or 500 mg/kg bw/day (groups II to IV) for 24 months. Control animals received untreated diet (Group I). Animals were regularly observed for clinical signs of toxicity and body weights and food consumption were measured. Interim necropsies were performed at 6 and 12 months (10/sex/dose). Ophthalmoscopic examination, haematology, clinical chemistry and urinalysis were performed at months 3, 6, 12, 18 and 24. Histopathological examinations were conducted on all animals that died or had to be killed in extremis. In addition, histopathological examinations were conducted for 10 animals/sex for groups I and IV at 6 months and for all survivors in Groups I and IV at 24 months. The mean body weight values for the high dose males were slightly reduced (5-10%) from week 16 to 87. Mean food consumption values for the high dose males were generally comparable to or greater than those of the control group (3-17%) during most weeks. In the high dose group, statistically significant changes to organ weights occurred (adrenal glands, spleen, liver, pituitary). No treatment-related gross lesions or histopathological findings occurred in any of the groups. The NOAEL for carcinogenicity and general toxicity was concluded to be at least 500 mg active acid/kg bw/day (BioDynamics Inc., 1979c, Reliability 2).
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.