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EC number: 205-086-5 | CAS number: 132-98-9
- 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
Endpoint summary
Administrative data
Description of key information
Penicillin V oral (Penicillin V potassium, Phenoxymethyl penicillin) and parenteral (Phenoxymethylpenicillin Benzathine) formulations are indicated in the treatment of mild to moderately severe infections due to penicillin sensitive microorganisms and have been widely used in human medicine for several decades having a well defined safety profile.
No relevant systemic toxic effects were noted in the acute inhalation toxicity studies.
Penicillin V has low acute toxicity with oral LD50 > 4000 mg/kg in mouse and LD50 > 1040mg/kg in rat. Due to the long term use it is well established that penicillins have a minimal direct toxicity to animals and man, and toxic effects of non-allergic nature have only been observed after extremely high doses. At oral administration the target organ is gastrointestinal tract. Penicillin Vis generally well tolerated in humans but may occasionally cause transient nausea, diarrhoea and allergic reactions. It is well known that changes in the intestinal flora occur in all individuals treated orally with penicillin. The degree of alteration is related directly to the quantity administered. This effect is usually of no clinical significance and the normal microflora is re-established shortly after therapy is stopped.
Safety after single administration
A large oral overdose of phenoxymethylpenicillin may cause nausea, vomiting, stomach pain, diarrhoea, and rarely, major motor seizures. If other symptoms are present, consider the possibility of an allergic reaction. Hyperkalaemia may result from overdose, particularly in patients with renal insufficiency (Sandoz, 2015).
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Species:
- rat
- Key result
- Dose descriptor:
- LD50
- Effect level:
- > 2 220 mg/kg bw
- Remarks on result:
- other: LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)
- Clinical signs:
- other: other:
- Interpretation of results:
- GHS criteria not met
- Endpoint:
- acute toxicity: oral
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Remarks:
- Data on Penicillin V free base
- Adequacy of study:
- supporting study
- Study period:
- 1958
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Species:
- mouse
- Route of administration:
- oral: unspecified
- Key result
- Effect level:
- ca. 6 578 mg/kg bw
- Remarks on result:
- other:
- Clinical signs:
- other: other:
- Interpretation of results:
- GHS criteria not met
- Endpoint:
- acute toxicity: oral
- Type of information:
- not specified
- Adequacy of study:
- supporting study
- Study period:
- 1971
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- GLP compliance:
- not specified
- Species:
- rat
- Route of administration:
- oral: unspecified
- Key result
- Dose descriptor:
- LD50
- Effect level:
- > 1 040 mg/kg bw
- Remarks on result:
- other: low acute oral toxicity
- Clinical signs:
- other: other:
- Interpretation of results:
- Category 4 based on GHS criteria
- Conclusions:
- Based on published data
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 1 040 mg/kg bw
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 06 June 2019 - 14 November 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Version / remarks:
- adopted 07 September 2009
- Deviations:
- yes
- Remarks:
- Relative humidity during the inhalation exposure
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.2 (Acute Toxicity (Inhalation))
- Version / remarks:
- Official Journal L 142, 31/05/2008
- Deviations:
- yes
- Remarks:
- Relative humidity during the inhalation exposure
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.1300 (Acute inhalation toxicity)
- Version / remarks:
- August 1998
- Deviations:
- yes
- Remarks:
- Relative humidity during the inhalation exposure
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- acute toxic class method
- Limit test:
- yes
- Specific details on test material used for the study:
- Test item: Pen V Potassium
Lot No.: B519322
Appearance:White solid powder
Manufacturing date:April 2019
Expiry date: 30 April 2024
Storage:Room temperature (15-25°C), protected from light
Safety precautions: Routine safety precautions were applied (lab coat, mask, gloves, safety glasses) - Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Rats are the preferred species of choice as historically they have been used for safety evaluation studies and they are specified by the appropriate regulatory authorities. The Wistar rat was selected due to a wide range of experience with this strain of rat in toxicity studies.
Hygienic level at arrival: SPF
Hygienic level during the test: Good conventional
Justification of strain: Same strain was used in the preliminary and in the main tests
Number of animals: 2 animals in the sighting exposure (1 male and 1 female) 10 animals in the main study (5 males and 5 females)
Sex:Male and female. Females were nulliparous, non-pregnant
Age of animals: Young adult rats, 8-12 weeks old (at start of the study) Bodyweight range at starting: The weight variation did not exceed ± 20% of the mean weight for either sex
Acclimatization time: 19 days (sighting exposure), 34 days (main study)
Husbandry
Animal health: Only healthy animals were used. The breeder certified the healthy status.
Hygienic level during the test: Good conventional Animal room number: 401/7
Housing: Group caging (up to 3 animals, by sex, per cage)
Cage type:Polypropylene/polycarbonate (type III) with stainless steel mesh lids.
Bedding: Laboratory bedding
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature:22 ± 3 °C
Relative humidity: *30 - 70 %
Ventilation: Above 10 air exchanges/hour by central air-conditioning system.
Housing/Enrichment: Rats were group-housed to allow social interaction, and with deep wood sawdust bedding, to allow digging and other normal rodent activities.
The temperature and relative humidity were checked and recorded daily during the study. Before housing the animals, the microbiological status of the room was checked.
Food and Water supply
Animals received ssniff® SM R/M-Z+H "Autoclavable complete feed for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum. Food was changed at weekly intervals. The food is periodically analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Copy of the relevant Certificate of Analysis of the diet is attached to the Report as Appendix 6. Copies of the relevant Certificates of Analysis are maintained in TOXI-COOP ZRT.’s archive. Animals received tap water from municipal supply, as for human consumption, from watering bottles ad libitum. Fresh drinking water was given daily. The drinking water is periodically analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Copies of the relevant Certificates of Analysis are maintained in TOXI-COOP ZRT.’s archive.
Bedding
SAFE 3/ 4-S-FASERN, Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH+Co.KG (Holzmühle 1, D-73494 Rosenberg, Germany) was used in the study. The quality of the bedding material is guaranteed by the supplier. Cages and bedding material were changed twice a week. A copy of the relevant certificate is retained in the archives of TOXI-COOP ZRT.The bedding is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- clean air
- Mass median aerodynamic diameter (MMAD):
- ca. 2.4 µm
- Geometric standard deviation (GSD):
- ca. 2.29
- Remark on MMAD/GSD:
- The MMADs and GSDs were within the respective target ranges. In conclusion, the particle size distributions obtained was considered to be appropriate for this type of study.
- Details on inhalation exposure:
- The test item was aerosolised using a Wright Dust Feeder II. (CH Technologies (USA), Inc., 263 Center Ave, Westwood, NJ 07675, USA; Serial Number: 052) located at the top of the exposure chamber. Compressed air was supplied by means of an oil-free compressor and passed through a suitable filter system prior to introduction to the dust generator.
- Analytical verification of test atmosphere concentrations:
- yes
- Remarks:
- The actual concentration of generated atmosphere was measured gravimetrically at regular intervals during exposures by pulling a suitable, known volume of test atmosphere from the exposure chamber, through GF10 glass fibre filters .
- Duration of exposure:
- ca. 4 h
- Remarks on duration:
- The animals were exposed to an atmosphere of the test item for a single, continuous four-hour period, generated according to the system and flow rates determined during the technical trials. The four-hour exposure period
- Concentrations:
- 5 mg/L
- No. of animals per sex per dose:
- A group of ten animals (five males and five females) was exposed for a four-hour period to the target concentration of 5 mg/L.
- Control animals:
- no
- Details on study design:
- The animals were held in polycarbonate restraining tubes and exposed “nose-only” under dynamic air flow conditions, using an anodised aluminium Flow Past Exposure Chamber (TSE Systems GmbH, Bad Homburg, Germany). Validation of this type of system was published by J. Pauluhn. (1994). The exposure unit was placed in closed hood in order to avoid cross-contamination and contamination of the laboratory environment. Fresh aerosol from the generation system was constantly supplied to the inner plenum (distribution chamber) of the exposure system from where, under positive pressure, it was distributed to the individual exposure ports. The animals were held in polycarbonate restraint tubes located around the chamber which allowed only the animal’s nares to enter the exposure port. After passing through the animal’s breathing zone, used aerosol entered the outer cylinder from where it was exhausted through a suitable filter system. Atmosphere generation was therefore dynamic. A schematic diagram of the exposure system is presented in Figure 1. Airflows and relative pressures within the system were constantly monitored and controlled by the computer system thus ensuring a uniform distribution and constant flow of fresh aerosol to each exposure port (breathing zone). The flow of air through each port was at least 0.7 L/min. This flow rate was considered adequate to minimise re-breathing of the test atmosphere as it is about twice the respiratory minute volume of a rat.Homogeneity of the test atmosphere within the test chamber and amongst the exposure ports was not specifically determined during this study. However, chambers of this design have been fully validated and have shown to produce evenly distributed atmospheres in the animals’ breathing zones (J. Pauluhn, 1994).
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 5.07 mg/L air
- Based on:
- test mat. (dissolved fraction)
- Exp. duration:
- 4 h
- Mortality:
- No mortality was observed
- Clinical signs:
- other: In Group 1 (5.07 mg/L), red staining on snout (2/5♂, 1/5♀) and dyspnoea (5/5♂, 5/5♀) were observed in animals during and/or after the exposure. All clinical signs ceased from the day following exposure until the end of the observation period.
- Body weight:
- Slight bodyweight loss was noted in two male exposed animals on the day following exposure and in four males during period Day 1-3 of the observation period. In further animals normal bodyweight gain was noted during whole observation period.
- Gross pathology:
- A single four hours nose-only exposure of test item Pen V Potassium to Han: WIST of Wistar origin rats followed by a 14-day observation period at the mean achievedtest concentration of 5.07 mg/L was not associated with any test item-related macroscopic findings on the exposed animals, except one case where right side pyelectasis was observed in one male.
- Other findings:
- Under the experimental conditions of this study, no death occurred in a group of 10 rats exposed to the mean achieved test concentration of 5.07 mg/L of Pen V Potassiumfor 4 hours. The acute inhalation median lethal concentration of Pen V Potassium, in Han: WIST of Wistar origin rats is therefore considered to be greater than 5.07 mg/L.
- Interpretation of results:
- GHS criteria not met
- Remarks:
- Based on the results of the current study Pen V Potassium is non-toxic after acute inhalative administration.The study result triggers the following classification/labelling: - Regulation (EC) No 1272/2008 (CLP): none
- Conclusions:
- The acute inhalation LC50 of the test substance in Wistar rats is >5.07 mg/L.
- Executive summary:
This study was performed to assess the acute inhalation toxicity of Pen V Potassium following a 4 hour exposure at the mean achieved concentration of 5.07 mg/L to 5 male and 5 female rats. A single sighting exposure was performed prior to the main study with 1 maleand 1 female at the target concentration of 5 mg/L.The main study group, consisting of 10 Han: Wistar rats (5 males and 5 females), was exposed to the target concentration of Pen V Potassium of 5 mg/L. The animals were exposed for 4 hours using a nose-only exposure system, followed by a 14-day observation period. The day of exposure was designated Day 0. Aerosol concentration was measured gravimetrically. The particle size distribution of the test aerosol was determined regularly during the exposure period. Clinical observations and bodyweights were recorded throughout the study and at the end of the scheduled period the surviving animals were euthanised and subjected to a gross examination post mortem. The quality of the test atmosphere fully complied with criteria documented in the respective guidelines: OECD No. 403, EPA OPPTS 870.1300 and Council Regulation (EC) No 440/2008. Under the experimental conditions of this study, no death occurred in a group of 10 rats exposed to the mean achieved test concentration of 5.07 mg/L of Pen V Potassiumfor 4 hours. The acute inhalation median lethal concentration of Pen V Potassium, in Han: WIST of Wistar origin rats is therefore considered to be greater than 5.07 mg/L.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LC50
- Value:
- 50.7
Additional information
Justification for classification or non-classification
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.