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EC number: 953-863-9 | CAS number: -
- 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: dermal
Administrative data
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2015-05-26 to 2015-08-10
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was performed in accordance with standard test protocols (OECD 402) 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 guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- 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-methyl-2-pyrrolidinyl)pyridine
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: S&K LAP Kft.
2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: Young adult rabbits, nulliparous and non-pregnant, females were 11 weeks old, males were 11 weeks old
- Weight at study initiation: Body weight range in main study
at starting (males, group 1): 2210 - 2310 g
Body weight range in main study
at starting (females, group 1): 2420 - 2776 g
Body weight range in main study
at starting (females, group 2): 2606 - 2780 g
Body weight range in main study
at starting (females, group 3): 2500 - 2656 g
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): CRLT/ny rabbit diet produced by Szindbád Kft., 2100 Gödöllő, Szárítópuszta, Hungary, ad libitum
- Water (e.g. ad libitum): tap water from watering bottles ad libitum
- Acclimation period: 5 days in females and 6 days in males
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10-15 air exchanges/hour by central air-condition system
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.
IN-LIFE DATES: From: 0 To: 15
Administration / exposure
- Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
- Area of exposure: back of animals
- % coverage: 10%
- Type of wrap if used: The entire trunk of the animal was wrapped with semi occlusive plastic wrap
REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test item was removed using body temperature water
- Time after start of exposure: 24-hour exposure period - Duration of exposure:
- 24-hour exposure period
- Doses:
- Preliminary study: 1000, 200, 50 and 5 mg/kg bw dose in females
Main study: 200, 100 and 50 mg/kg bw dose in females and 50 mg/kg bw dose in males - No. of animals per sex per dose:
- Preliminary study: n=2 animals/dose
Main study: n=5 animals/sex/dose - Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
Observations
Mortality
Inspection for signs of morbidity and mortality were made twice daily at the beginning and end of the working day.
Clinical observations
Careful clinical observation was made at the following intervals: 1h, 5h after the treatment and once each day for 14 days thereafter in preliminary study and 30 min., 1h, 2h, 3h, 4h and 5h after the treatment and once each day for 14 days thereafter in main study.
Individual observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern as well. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body weight
The body weight was recorded on day 0 (shortly before the treatment) in preliminary study and on day -1, on day 0 (just before the treatment), on day 1, on day 7 and on day 15 in main study. The precision was 1 g.
Pathology
All animals were subjected to gross pathology in main study. All survivor rabbits were sacrificed under EUTHANIMAL 40% anaesthesia (approx. 0.25 ml/kg). 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.
Animals of preliminary study were humanely sacrificed on Day 14. - Statistics:
- 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.
Results and discussion
Effect levelsopen allclose all
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 70.4 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 28.3 - <= 131.2
- Sex:
- female
- Dose descriptor:
- other: LOAEL
- Effect level:
- 50 mg/kg bw
- Based on:
- test mat.
- Mortality:
- In males, no mortality observed over a 14-day period following a 24-hour dermal exposure to Nicotine of group 1 treated with 50 mg/kg bw dose.
One out of five females treated with 50 mg/kg bw dose died on the treatment day 2 hours after the treatment. Four out of five females treated with 100 mg/kg bw dose died during the study. One animal died on Day 1. On the treatment day, one animal died 5 hours after the treatment, one animal died 1 hour after the treatment and one animal died 2 hours after the treatment. All females treated with 200 mg/kg bw dose died on the treatment day. Four animals died 1 hour after the treatment and one animal died 2 hours after the treatment, as well.
All deaths seemed to be consequences of systemic toxic effect of the test item.
The males were not more sensitive than females on the basis of this study. - Clinical signs:
- other: Males: Group 1 (50 mg/kg bw): No treatment related systemic toxic symptoms were observed throughout the post-treatment period. Females: Group 1 (50 mg/kg bw):Decreased activity (1 case of 82 observations), tremor (1/82), incoordination (1/82), lateral pos
- Gross pathology:
- Altogether 10 female rabbits died spontaneously during the study. All male rabbits and five female animals survived until the scheduled necropsy on Day 15.
Males
External necropsy findings as crusting (2 animals) and wound (2 animals) on the treated site of skin was observed in group treated with 50 mg/kg bw dose
No gross pathology findings were found in one male during the macroscopic examination. These findings could be related to the test item irritant effect.
Females
In 50 mg/kg bw dose group, external finding as slight redness on the treated site was observed in one animal. It could be related to the test item irritant effect.
In 100 mg/kg bw dose group, an internal necropsy finding as autolysis was observed in one animal. It is normal physiological process after death. Severe hydrometra was observed in two animals. The hydrometra is physiological finding and connected to the cycle of the animal. External finding as slight redness on the treated site was observed in three animals and moderate redness on the treated site was recorded in one animal. Besides, slight oedema was detected in one animal. The redness and oedema could be related to the test item irritant effect.
In 200 mg/kg bw dose group, an internal necropsy finding as slight hydrometra was observed in two animals and moderate hydrometra was recorded in one animal. The hydrometra is physiological finding and connected to the cycle of the animal.
External finding as severe redness on the treated site was observed in four animals and moderate redness on the treated site was recorded in one animal. Slight oedema was detected in one animal and moderate oedema on the treated site was found in two animals. The redness and oedema could be related to the test item irritant effect. - Other findings:
- Dermal irritation symptoms were observed on the treatment site in both sexes.
In males treated with 50 mg/kg bw dose (group 1), very slight redness (score 1), well defined redness (score 2) and moderate to severe redness (score 3) was observed in one animal between Day 1 and Day 7. Moderate to severe redness (score 3) and severe redness (score 4) was detected in two animals between Day 1 and Day 7. Very slight redness (score 1) and well defined redness (score 2) was recorded in one animal between Day 1 and Day 7. Very slight redness (score 1) occurred in one animal between Day 1 and Day 5. Another sign as desquamation appeared in four animals on Day 6 and in one animal on Day 7. Crusting was recorded in four animals. It was observable between Day 7 and Day 14. Wound was found in two animals. It was observable between Day 11 and Day 14.
One male became free of skin irritation symptoms by Day 10.
In females treated with 50 mg/kg bw dose (group 1), very slight redness (score 1) was observed in two animals on Day 1. Well defined redness (score 2) and very slight redness (score 1) was detected in one animal on Day 1 and on Day 2, respectively. Moderate to severe redness (score 3) and well defined redness (score 2) was recorded in one animal on Day 1 and on Day 2, respectively.
Very slight redness (score 1) occurred in one animal treated with 100 mg/kg bw dose (group 2) on Day 1.
The survivor females became free of skin irritation symptoms by Day 3.
There was no oedema observed during the 14-day observation period in both sexes, but it was observable in females of group 2 and 3 on necropsy day.
Any other information on results incl. tables
Summary of lethality - Post-treatment observation period (14 days)
Females
Test item | Group | Dose (mg/kg bw) | Lethality |
Nicotine | 1 | 50 | 1/5 |
Nicotine | 2 | 100 | 4/5 |
Nicotine | 3 | 200 | 5/5 |
Remark: LD50 (females)= 70.4 mg/kg bw [95% Confidence limits: 29.3; 131.2]
Males
Test item | Group | Dose (mg/kg bw) | Lethality |
Nicotine | 1 | 50 | 0/5 |
Applicant's summary and conclusion
- Interpretation of results:
- Toxicity Category II
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Under the experimental conditions, the acute dermal LD50 value of the test item Nicotine is 70.4 mg/kg bw in female NZW rabbits on basis of statistical test (Probit analysis by SPSS+software). The confidence interval is 28.3 and 131.2 mg/kg bw.
The males are not more sensitive than females based on mortality. - Executive summary:
An acute dermal toxicity study was performed with test item Nicotine in NZW rabbits. A full test was carried out on basis of a preliminary study. First, three groups of female animals (n=5 animals/dose) were exposed to Nicotine at 50, 100 and 200 mg/kg bw test item by dermal route. After completion of the study in female sex, one group of 5 males was dosed at 50 mg/kg bw test item by dermal route. Test item was applied in undiluted form and left in contact with the skin for 24 hours, followed by a 14-day observation period.
Mortality
All male rabbits dosed at 50 mg/kg bw test item survived until the end of the 14-day observation period. All female rabbits dosed at 200 mg/kg bw test item died on the treatment day between 1 and 2 hours after the treatment. Four female rabbits dosed at 100 mg/kg bw test item died between the treatment day and Day 1. One female rabbit dosed at 50 mg/kg bw test item died on the treatment day 2 hours after the treatment. The mortalities seemed to be consequences of systemic toxic effect of the test item and were correlated with the systemic clinical symptoms. The LD50 value is 70.4 mg/kg bw in females. The 95 % confidence limits as follows: lower is 28.3 mg/kg bw and upper is 131.2 mg/kg bw. The males were not more sensitive than females on the basis of this study.
Systemic clinical symptoms, local dermal symptoms
In males treated with 50 mg/kg bw dose, no systemic clinical symptoms were observed during the study. In females treated with 50 mg/kg bw dose, CNS symptoms (decreased activity, tremor), disturbances of coordination (incoordination, lateral position) and disturbance of the autonomic functions (dyspnoea) were observed on the treatment day 1 hour after the treatment. In females treated with 100 mg/kg bw dose, CNS symptoms (decreased activity, tremor, closed eyes, clonic convulsion), disturbance of coordination (abnormal gait) and disturbances of the autonomic functions (increased respiration rate, dyspnoea) were observed on the treatment day between 30 min. and 5 hours after the treatment. In females treated with 200 mg/kg bw dose, CNS symptoms (decreased activity, tremor, closed eyes, clonic convulsion), disturbance of coordination (abnormal gait) and disturbance of the autonomic functions (salivation) were observed on the treatment day between 30 min. and 1 hour after the treatment.
The test item caused dermal irritation symptoms on the treatment site in both sexes. In males, very slight to severe erythema was observed between Day 1 and Day 7 and other signs as desquamation, crusting and wound were detected between Day 6 and the necropsy day, as well. In females, very slight to severe erythema was recorded in 50 mg/kg bw dose group between treatment day and Day 2. Very slight to severe erythema and slight oedema was found in 100 mg/kg bw dose group between treatment day and Day 1. Moderate to severe erythema and slight to moderate oedema was detected in 200 mg/kg bw dose group on the treatment day.
Body weight, body weight gain
The body weight development was undisturbed in all survivor animals, except one female treated with 50 mg/kg bw dose on second week. This body weight loss can be evaluated as an individual variation without toxicological meaning.
Gross pathology
The macroscopic external necropsy findings on the treated site as erythema, oedema, crusting and wound were related to the local irritant effect of the test item. No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy.
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