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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 200-193-3 | CAS number: 54-11-5
- 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:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: The study was performed in accordance with standard test protocols (OECD 425) in a quality controlled laboratory. The study is valid according to criteria mentioned in the test protocols.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
- Deviations:
- yes
- Remarks:
- 95% Confidence intervals could not be calculated.
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- up-and-down procedure
- Limit test:
- no
Test material
- Reference substance name:
- Nicotine
- EC Number:
- 200-193-3
- EC Name:
- Nicotine
- Cas Number:
- 54-11-5
- Molecular formula:
- C10H14N2
- IUPAC Name:
- 3-(1-methylpyrrolidin-2-yl)pyridine
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- NMRI
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: TOXI COOP ZRT. Cserkesz u. 90., 1103 Budapest, Hungary
- Age at study initiation: 8 weeks old in first, second and third step and 9 weeks old in fourth, fifth, sixth, seventh, eighth and ninth step
- Weight at study initiation: +/- 20% of mean weight
- Fasting period before study: The day before treatment the animals were fasted. The food, but not water was withheld for 3-4 hours.
- Housing: 3 animals/cage during acclimatization, individually after the treatment
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days in first step, 7 days in second step, 9 days in third step, 11 days in fourth step, 12 days in fifth step, 13 days in sixth step, 14 days in seventh step, 16 days in eighth step and 17 days in ninth step
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10-15 air exchanges/hour by central air-condition system
- Photoperiod (hrs dark / hrs light): Artificial light, from 6 a.m. to 6 p.m.
IN-LIFE DATES: From: Day 0 To: Day 14
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: The test item was applied in a concentration of 1.75, 5.5, 17.5 and 55 mg/mL
- Amount of vehicle (if gavage): Concentration of formulations was adjusted to maintain a treatment volume of 10 mL/kg bw - Doses:
- 17.5; 55; 175; 550 mg/kg bw. The first animal was dosed a step below the best preliminary estimate of the LD50. The dose progression factor was 3.2.
- No. of animals per sex per dose:
- Group 1 (17.5mg/kg bw): 3 animals
Group 2 (55mg/kg bw): 3 animals
Group 3 (175mg/kg bw): 2 animals
Group 4 (550mg/kg bw): 1 animal - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days (see below)
- Necropsy of survivors performed: yes (see below)
Mortality
Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each day for 14 days
General state, external appearance, behavior and clinical symptoms
Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body weight
The body weights were recorded on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g.
Necropsy
All survivor mice were sacrificed under isofluran anaesthesia at the end of the observation period. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed, and any abnormality was recorded with details of its location, colour, shape and size. - Statistics:
- The using doses were given by a software program: AOT425StatPgm.
Calculation of the results was performed with the help of validated software. The estimation of the biological data was accomplished using the Probit analysis by SPSS+software.
The 95%-confidence limits were not calculated by statistical test (Probit analysis by SPSS+software), because their range is too wide.
Results and discussion
Effect levels
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- ca. 77.83 mg/kg bw
- Based on:
- test mat.
- Mortality:
- The animal treated with 550 mg/kg bw dose (group 4) died on the treatment day 10 sec after the treatment.
The animal treated with 175 mg/kg bw dose (group 3) died on the treatment day 10 sec after the treatment. The other animal of this dose group survived until the end of the 14-day observation period.
Two animals treated with 55 mg/kg bw dose (group 2) died on the treatment day 20 sec and 30 minutes after the treatment, respectively. The third animal of this dose group survived until the end of the 14-day observation period.
There was no deaths in 17.5 mg/kg bw dose (group 1), all three animals survived until the end of the 14-day observation period.
The deaths were related to the systemic toxic effect of the test item.
The LD50 value is 77.83 mg/kg bw on basis of statistical test (Probit analysis by SPSS+software). The approximate 95 % confidence limits were not calculated because their range is too wide. - Clinical signs:
- other: In the group 1 (17.5 mg/kg bw), CNS - and emotion symptoms (decreased activity, tremor, clonic convulsion), disturbance of coordination (abnormal gait) and disturbance of the autonomic functions (dyspnoea) were observed in animals on the treatment day bet
- Gross pathology:
- Altogether 9 mice were treated with the test item. Four animals died spontaneously during the study. Five animals survived until the end of study.
No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.
Any other information on results incl. tables
Summary of Lethality - Post-treatment observation period (14 days), Females
|
Applicant's summary and conclusion
- Interpretation of results:
- Toxicity Category III
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- It can be concluded, that the LD50 value of test item Nicotine is 77.83 mg/kg bw, given to mice orally for single application on basis of statistical test (Probit analysis by SPSS+software). However, the 95 % confidence limits could not calculated because their range is too wide.
- Executive summary:
The Up-and-Down-Procedure (OECD 425) was performed to determine the acute oral toxicity of the test item Nicotine in mice.
General information
The first animal was dosed a step below the best preliminary estimate of the LD50. The initial dose was 17.5 mg/kg bw. The first animal survived until 48 hours after the treatment, so the second animal received a higher dose as 55 mg/kg bw. The second animal survived until 48 hours after the treatment, so the third animal received a higher dose as 175 mg/kg bw. The third animal survived until the 48 hours after the treatment, so the fourth animal received a higher dose as 550 mg/kg bw. The fourth animal died on the treatment day, so the fifth animal received a lower dose as 175 mg/kg bw. The fifth animal died on the treatment day, so the sixth animal received a lower dose as 55 mg/kg bw. The sixth animal died on the treatment day, the seventh animal received a lower dose as 17.5 mg/kg bw. The seventh animal survived until the 48 hours after the treatment, so the eighth animal received a higher dose as 55 mg/kg bw dose. The eighth animal died on the treatment day, so the ninth animal received a lower dose as 17.5 mg/kg bw. The ninth animal survived until the end of study. Dosing was stopped, because the stopping criteria according to the Guideline was met: LR criterion (if the likelihood-ratios calculated exceed the critical likelihood-ratio, the LR stopping criterion is satisfied and testing stops). The dose progression factor was 3.2. The first, second, third and seventh survivor animal was observed for up to 48 hours before the next animal treated. Dosing was stopped, because the maximum number of animals tested. The doses were given by a software program: AOT425StatPgm. All animals were periodically weighed, observed for clinical and behavioral symptoms. Gross pathological examination was carried out on the treatment day and 15th day after the treatment.
Lethality, Clinical symptoms and Body weight
The mouse treated with 550 mg/kg bw dose of test item died on the treatment day 10 seconds after the treatment. One out of two mice treated with 175 mg/kg bw dose died on the treatment day 10 seconds after the treatment. Two out of three mice treated with 55 mg/kg bw dose died on the treatment day 20 seconds and 30 minutes after the treatment, respectively. No lethality was noted at single oral dose (gavage) of 17.5 mg/kg bw. In the group 1 (17.5 mg/kg bw), CNS - and emotion symptoms (decreased activity, tremor, clonic convulsion), disturbance of coordination (abnormal gait) and disturbance of the autonomic functions (dyspnoea) were observed in animals on the treatment day between 30 min. and 3 hours after the treatment. In the group 2 (55 mg/kg bw), CNS - and emotion symptoms (decreased activity, tremor, tonic convulsion, clonic convulsion, closed eyes) and disturbance of the autonomic functions (dyspnoea) were observed in animals on the treatment day between 30 min. and 4 hours after the treatment.
In the group 3 (175 mg/kg bw), CNS - and emotion symptoms (decreased activity, tremor, closed eyes, clonic convulsion) and disturbance of the autonomic functions (decreased respiration rate, dyspnoea) were observed in animals on the treatment day between 30 min. and 4 hours after the treatment, except clonic convulsion, which appeared 10 seconds after the treatment. In the group 4 (550 mg/kg bw), CNS - and emotion symptoms (tonic convulsion, clonic convulsion) were observed in animals on the treatment day 10 seconds after the treatment. The body weight development was undisturbed in all survivor animals.
Gross pathology
The animal of group 4, one animal of group 3 and two animals of group 2 died spontaneously on the treatment day. One animal of group 3, one animal of group 2 and all animals of group 1 survived until the end of the 14-day observation period. No pathological changes were found related to the effect of the test item during the macroscopic examination of the animals.
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.