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EC number: 200-607-2 | CAS number: 65-31-6
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- secondary literature
- Justification for type of information:
- Data from peer reviewed journal
Data source
Reference
- Reference Type:
- publication
- Title:
- Sperm function and fertility profile of test material in male rats
- Author:
- P. Oyeyipo et al.
- Year:
- 2 014
- Bibliographic source:
- International Journal of Green Pharmacy, 2014
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- Reproductive toxicity study of test material was performed on male albino rats.
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- No data available
Test material
- Reference substance name:
- Nicotine dihydrogen ditartrate
- EC Number:
- 200-607-2
- EC Name:
- Nicotine dihydrogen ditartrate
- Cas Number:
- 65-31-6
- Molecular formula:
- C10-H14-N2.2C4-H6-O6
- IUPAC Name:
- nicotine dihydrogen ditartrate
- Details on test material:
- - Name of test material: Nicotine dihydrogen tartrate
- Molecular formula: C10H14N2.2C4H6O6
- Molecular weight: 462.4054 g/mol
- Substance type: Organic
- Physical state: No data
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: albino rats
- Details on species / strain selection:
- No data available
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Details on test animals and env. conditions
TEST ANIMALS
- Source: Animal House, College of Medicine,
University of Ibadan, Oyo State, Nigeria
- Age at study initiation: 8-10 weeks old
- Weight at study initiation: average weight ranged between 150 and 180 g
- Fasting period before study:
- Housing:
- Use of restrainers for preventing ingestion (if dermal):
yes/no
- Diet (e.g. ad libitum): ad libitum access to rat chow food
- Water (e.g. ad libitum): ad libitum access to drinking water.
- Acclimation period:
ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12:12‑hour light–dark
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- physiological saline
- Details on exposure:
- Details on exposure
PREPARATION OF DOSING SOLUTIONS:
Test material dissolved in normal saline
DIET PREPARATION
- Rate of preparation of diet (frequency):No data available
- Mixing appropriate amounts with (Type of food )
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water):
- Concentration in vehicle: 0, 1.0 mg/kg bw/day
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Other: The working solutions were stored in foil‑wrapped glass bottle at 4°C for no longer than 10 days - Details on mating procedure:
- - M/F ratio per cage:4:5
- Length of cohabitation: 5days
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:The presence of a vaginal plug was accepted as the index for a positive mate and taken as day one of pregnancy
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: [no / yes (explain)]
- After successful mating each pregnant female was caged (how):
- Any other deviations from standard protocol: - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 30 days
- Frequency of treatment:
- Daily
- Details on study schedule:
- No data available
Doses / concentrations
- Remarks:
- 0, 1.0mg/kg bw/day
- No. of animals per sex per dose:
- 32 male rats
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
- Positive control:
- No data available
Examinations
- Parental animals: Observations and examinations:
- Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: yes
DETAILED CLINICAL OBSERVATIONS: Yes
Time schedule: daily
BODY WEIGHT: Yes
Time schedule for examinations: daily
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes Food consumption was determined weekly.
Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day:
Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
Time schedule for examinations:
OTHER: - Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- Parameters examined in {P} male parental generations:
testis weight, epididymis weight, daily sperm production, sperm count in testes, sperm count in epididymides, , sperm motility, sperm morphology, were observed - Litter observations:
- The number of litters delivered and their body weights were determined.
- Postmortem examinations (parental animals):
- No data available
- Postmortem examinations (offspring):
- No data available
- Statistics:
- Data obtained were expressed in Mean ± SEM. Statistical analysis was performed by analysis of variance (ANOVA) followed by multiple comparison by two‑tailed t‑test. The values for P < 0.05 were considered to be statistically significant.
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- effects observed, treatment-related
- Description (incidence and severity):
- Oral administration of 1.0 mg/kg BW of test material on animals daily for a period of 4 weeks significantly
decrease (P < 0.05) the progressive motility of the sperm when compared with the control group
The mean epididymal sperm count of animals administered with 1.0 mg/kg BW was significantly decreased (P < 0.05) when compared with their control
A significant decrease (P > 0.05) was recorded for the mean percentage live sperm of rats treated with 1.0 mg/k bw when compared with the control
The test material caused an insignificant decrease (P > 0.05) in the epididymal sperm volume in the treated groups when compared with the control
Administration of 1.0 mg/kg bw test material significantly reduced normal sperm morphology
The mean serum testosterone level of animals that received 1.0 mg/kg bw of nicotine was significantly decreased (P < 0.05) when compared with the control group. - Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- Administration of 1.0 mg/kg bw test material caused significant decrease in libido score when compared with the control, test material significantly decreased percentage fertility when compared with the control
Effect levels (P0)
- Dose descriptor:
- LOAEL
- Effect level:
- 1 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- reproductive function (sperm measures)
- reproductive performance
- Remarks on result:
- other: effects observed treatment related
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- not specified
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not specified
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not specified
Effect levels (F1)
- Dose descriptor:
- other: not specified
- Generation:
- other: not specified
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- other: not specified
- Remarks on result:
- not measured/tested
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
Any other information on results incl. tables
Semen parameters of experimental rats treated with test material
Dose |
Motility (%) |
Live/dead (%) |
Volume (ml) |
Count (106/ml) |
ratio |
|
|
|
|
Control |
85.50±3.21 |
94.56±4.21 |
5.22±0.04 |
112.40±10.40 |
Nicotine |
|
|
|
|
1.0 mg/kg+ |
32.00±4.65* |
79.80±5.17* |
5.18±0.06 |
64.20±5.60* |
Values are expressed as means ± S.E.M of 8 rats per group. *P<0.05 vs control
Fertility profile of experimental rats treated with test material
Dose |
Libido score |
Litter number |
Litter weight (g) |
Percentage fertility |
Control |
8.82 ± 1.21 |
6.24 ±040 |
5.96± 0.20 |
100 |
1.0 mg/kg+ test material |
3.26 ±1.62* |
0.00 ±0.00* |
0.00 ±0.00* |
0* |
Values are expressed as means ± S.E.M of 8 rats per group. *P< 0.05 vs control
Applicant's summary and conclusion
- Conclusions:
- Low Observed Adverse Effect Level (LOAEL) was considered to be 1.0 mg/kg/day, When male albino rats were treated with test material orally.
- Executive summary:
Sperm function and fertility profile of test material was performed on 32 male albino rats whose average weight ranged between 150 and 180 g (8-10 weeks old). The test material dosage freshly prepared in normal saline for each group of animals was delivered orally at 1.0 mg/kg body weight (BW). The working solutions were stored in foil‑wrapped glass bottle at 4°C for no longer than10 days. A total of 20 untreated fertile, Proestrum female rats were used for the fertility test. Five untreated female rats were cohabited with each other of the four male groups from the day 31 of treatment. All animals were cohabited for 5 days. The presence of a vaginal plug was accepted as the index for a positive mate and taken as day one of pregnancy. The number of litters delivered and their body weights were determined. Oral administration of 1.0 mg/kg BW of test material on animals daily for a period of 4 weeks significantly decrease (P< 0.05) the progressive motility of the sperm when compared with the control group. The mean epididymal sperm count of animals administered with 1.0 mg/kg BW was significantly decreased (P< 0.05) when compared with their control. A significant decrease (P> 0.05) was recorded for the mean percentage live sperm of rats treated with 1.0 mg/k bw when compared with the control. The test material caused an insignificant decrease (P> 0.05) in the epididymal sperm volume in the treated groups when compared with the control. A significant decrease (P> 0.05) was recorded for the mean percentage live sperm of rats treated with 1.0 mg/k bw when compared with the control. The test material caused an insignificant decrease (P> 0.05) in the epididymal sperm volume in the treated groups when compared with the control. Administration of 1.0 mg/kg bw test material significantly reduced normal sperm morphology. The mean serum testosterone level of animals that received 1.0 mg/kg bw of nicotine was significantly decreased (P< 0.05) when compared with the control group.
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