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EC number: 200-709-7 | CAS number: 69-53-4
- 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
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Equivalent or similar to the OECD 451 Guideline.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 982
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Deviations:
- not specified
- GLP compliance:
- not specified
Test material
- Reference substance name:
- (2S,5R,6R)-6-{[(2R)-2-amino-2-phenylacetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate
- Cas Number:
- 7177-48-2
- Molecular formula:
- C16H25N3O7S
- IUPAC Name:
- (2S,5R,6R)-6-{[(2R)-2-amino-2-phenylacetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate
- Details on test material:
- - Name of test material (as cited in study report): Ampicillin trihydrate
- Lot/batch No.: 61849K; lot 33564-550 (week 72)
- Storage condition of test material: 4 ºC
- Other:
Maximum Storage Time: 2 weeks
Supplier: Ersana, Inc. (Humacao, Puerto Rico)
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, MI)
- Age at study initiation: 7-8 weeks of age
- Housing: All animals were housed five per cage; Polycarbonate (Lab Products, Int ., Rochelle Park, NJ)
- Diet (e.g. ad libitum): NIH 07 Rat and Mouse Ration (Zeigler Bros , Gardners, PA]; available ad libitum
- Water (e.g. ad libitum): City water from deep well passed through reverse osmosis unit to remove 90 % of the dissolved salts (Osmonics, Inc., Hopkins, MN); rats automatic watering system (Edstrom Industries, Waterford, WI); available ad libitum.
- Acclimation period: 18 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 66 - 81 ºF
- Humidity (%): 18 - 100%
- Air changes (per hr): 12 room air changes/h
- Photoperiod (hrs dark / hrs light): fluorescent light 12 h/d
IN-LIFE DATES: From 2/9/1980 to 23/8/1982
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- VEHICLE
- Justification for use and choice of vehicle (if other than water): Ampicillin trihydrate is only slightly soluble in water; therefore, corn oil was selected to improve suspendability in the gavage vehicle.
The test substance was initially prepared with corn oil as 30% or 15% (w/v) suspensions, mixed in Waring blender or Tekmer homogenizer. The suspension was divided into amounts needed daily.
- Amount of vehicle (if gavage): 5 mL/kg bw - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- See Table 1 "Overall remarks, attachments"
- Duration of treatment / exposure:
- 103 weeks
- Frequency of treatment:
- 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 750 and 1500 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 50
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
Doses for the 2-year study were selected because no dose-related organ toxicity, decreases in body weight gain, or deaths were seen in the 13-week studies at doses up to 3000 mg/kg body weight. Clinical signs in the 13-week study included diarrhea at 3000 mg/kg in male and female rats. The doses of ampicillin trihydrate used in the 2-year study were limited because the maximum concentration of the chemical in corn oil that could be used as a gavage suspension was determined to be 300 mg/mL; the maximum volume of corn oil administered in NTP 2-year studies is usually 5 mL/kg body weight for rats.
Examinations
- Observations and examinations performed and frequency:
- Observation: 2/day
Clinical signs: 1/week
Body weights: 1/week for 12 weeks, then 1/4 week
Palpation of animals: 1/month from 41 to 101 week - Sacrifice and pathology:
- Necropsy and histologic exam performed on all animals.
The following tissues were examined:
Gross lesions and tissue masses, blood smear, mandibular or mesenteric lymph nodes, salivary glands, sternebrae, femur or vertebrae including marrow, thyroid gland, parathyroids, small intestine, large intestine, liver, prostate/testes/epididymis or ovaries/uterus, lungs with mainstem bronchi, skin, heart, esophagus, stomach, brain, thymus, traches, pancreas, spleen, kidneys, adrenal glands, urinary bladder, pituitary gland, spinal cord (if neurologic signs present), eyes (if grossly abnormal), mammary glands and pharynx (if grossly abnormal)
Results and discussion
Results of examinations
- Details on results:
- - Body weight: Mean body weights of dosed male and female rats were similar or slightly increased over those of the corresponding vehicle control group throughout the studies.
- Diarrhea, chromodacryorrhea, and excessive urination were considered to be compound related.
- Survival: No significant differences in survival were observed between any groups of either sex.
PATHOLOGY:
Hematopoietic System: Mononuclear cell leukemia in male rats occurred with a significant positive trend, and the incidences in the dosed groups were greater than that in the vehicle controls. The incidence of mononuclear cell leukemia was not increased in dosed female rats. Hematopoietic hyperplasia of the bone marrow was reported at increased incidences in dosed male (vehicle control, 7/50, 14%; low dose, 16/48, 33%; high dose, 17/50, 34%) and female rats (13/50, 26%; 22/49, 45%; 25/50, 50%). Hematopoietic hyperplasia was frequently present in rats with malignant neoplasms in a variety of organs. Necrosis and inflammation associated with neoplasia may have provided the physiologic stimulus or demand for increased blood leukocytes and hematopoietic hyperplasia.
Adrenal Gland: Focal cellular change of the adrenal cortex was observed at increased incidence in high dose male and female rats (male: vehicle control, 1/50; low dose, 5/50; high dose, 7/49; female: 6/50; 12/50; 15/49). Pheochromocytomas and pheochromocytomas or malignant pheochromocytomas (combined) of the adrenal medulla in male rats occurred with significant positive trends, and the incidences in the high dose group were significantly greater than those in the vehicle controls. The incidences of focal hyperplasia of the adrenal medulla were not increased in dosed male rats relative to vehicle controls. Adrenal medulla lesions were not increased in female rats.
Mammary Gland: Hyperplasia was observed at an increased incidence in low dose male rats (vehicle control, 4/50; low dose, 11/50; high dose, 4/50). The incidence of mammary gland fibroadenomas was not increased in dosed male rats (1/50; 1/50; 0/50). The incidence of hyperplasia of the mammary gland was similar in dosed and vehicle control female rats (23/50; 23/50; 22/50). The incidence of fibroadenomas in low dose female rats was significantly greater than that in the vehicle controls by the incidental tumor test (P = 0.019) (16/50; 25/50; 19/50).
Thyroid Gland: C-cell hyperplasia was observed at increased incidences in low dose male and high dose female rats (male: vehicle control, 4/50; low dose, 11/48; high dose, 7/46; female: 10/50; 12/49; 21/49). The incidences of C-cell adenomas or carcinomas (combined) in dosed rats were not significantly different from those in the vehicle controls (male: 2/50; 6/48; 3/46; female: 2/50; 1/49; 1/49).
Liver: Cytoplasmic vacuolization was observed at increased incidences in high dose male rats (male: vehicle control, 2/50; low dose, 5/49; high dose, 10/50; female: 2/50; 4/50; 4/50).
Forestomach: Hyperkeratosis and acanthosis were observed at increased incidences in high dose male rats (hyperkeratosis: vehicle control, 3/48; low dose, 6/44; high dose, 9/45; acanthosis: 0/48; 2/44; 5/45). The incidences of hyperkeratosis (2/49; 1/50; 3/47) and acanthosis (0/49; 0/50; 0/47) were not increased in dosed female rats.
Prostate: Inflammation was observed at an increased incidence in high dose male rats (vehicle control, 22/49, 45%; low dose, 27/48, 56%; high dose, 36/47, 77%).
Eye: Retinal degeneration, cataracts, hemorrhage, and posterior synechia were observed at notably greater incidences in vehicle control rats of each sex than in the dosed groups. Vehicle control animals were positioned on the top two rows of the rack throughout the studies, and the appearance of eye lesions was probably due to the placement of the animals on the rack and proximity to the fluorescent light source rather than to chemical administration.
Applicant's summary and conclusion
- Conclusions:
- There was equivocal evidence that ampicillin is a carcinogen in male rats.
There was no evidence that ampicillin is a carcinogen in female rats. - Executive summary:
Groups of 50 rats of each sex were administered 0, 750, or 1500 mg/kg ampicillin trihydrate in corn oil by gavage, 5 days per week for 103 weeks (dose volume, 5 mL/kg body weight)
Necropsy and histologic exam performed on all animals.
The following tissues were examined: Gross lesions and tissue masses, blood smear, mandibular or mesenteric lymph nodes, salivary glands, sternebrae, femur or vertebrae including marrow, thyroid gland, parathyroids, small intestine, large intestine, liver, prostate/testes/epididymis or ovaries/uterus, lungs with mainstem bronchi, skin, heart, esophagus, stomach, brain, thymus, traches, pancreas, spleen, kidneys, adrenal glands, urinary bladder, pituitary gland, spinal cord (if neurologic signs present), eyes (if grossly abnormal), mammary glands and pharynx (if grossly abnormal)
Under the conditions of this 2- year gavage study, there was equivocal evidence of carcinogenicity of ampicillin trihydrate for male F344/N rats as shown by increased incidences of pheochromocytomas of the adrenal medulla and by marginally increased incidences of mononuclear cell leukemia. There was no evidence of carcinogenicity for female F344/N rats receiving 750 or 1500 mg/kg. Nonneoplastic lesions of the forestomach were seen in male rats.
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