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Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) for target chemical 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (Nicotine sulphate) (CAS no: 65-30-5) was considered based on different experimental studies conducted on rats. The LD50 value was considered to be 50 mg/kg bw in rats. All other acute oral studies in rat concluded that the LD50 value is between 50 - 300 mg/kg bw for rat. Thus, comparing these values with the criteria of CLP regulation, Nicotine sulphate can be classified as “Category 3” for acute oral toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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:
data from handbook or collection of data
Justification for type of information:
Data is from handbook.
Reference:
Composition 0
Composition 0
Composition 0
Composition 0
Composition 0
Composition 0
Composition 0
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Acute oral toxicity of 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (CAS no: 65-30-5) in rat.
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- IUPAC Name: 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid
- Common Name: Nicotine sulphate
- InChI: 1S/2C10H14N2.H2O4S/c2*1-12-7-3-5-10(12)9-4-2-6-11-8-9;1-5(2,3)4/h2*2,4,6,8,10H,3,5,7H2,1H3;
(H2,1,2,3,4)/t2*10-;/m00./s1
- Smiles: CN1CCC[C@H]1c2cccnc2.CN3CCC [C@H]3c4cccnc4.OS(=O)(=O)O
- Molecular formula:C10H16N2O4S
- Molecular weight :422.547 g/mol
- Substance type:Organic
- Physical state:Solid, white brown crystalline
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
not specified
Doses:
50 mg/kg bw
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
50 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50% mortality was observed
Mortality:
50% mortality was observed
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The acute oral LD50 value was considered to be 50 mg/kg bw, when rats were treated with 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (CAS no: 65-30-5) via oral route.
Executive summary:

Acute oral toxicity study of 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (CAS no: 65-30-5) was conducted in rats at the dose concentration of 50 mg/kg bw. 50% mortality was observed. Hence, LD50 value was considered to be 50 mg/kg bw, whenrats were treated with3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid via oral route.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
50 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from handbook.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity:

In different experimental studies, target chemical 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (Nicotine sulphate) (CAS no: 65-30-5) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for Nicotine sulphate. The studies are summarized as below –

The experimental study conducted on rats and mentioned in handbooks, authoritative databases and secondary sources for the target chemical 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (Nicotine sulphate) (CAS no: 65-30-5) was designed and conducted for acute oral toxicity. The acute oral toxicity study was conducted in rats at the dose concentration of 50 mg/kg bw. 50% mortality was observed. Hence, LD50 value was considered to be 50 mg/kg bw, when rats were treated with3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid via oral route.

In another experimental study conducted on rats and mentioned in publication and handbook for the target chemical 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (Nicotine sulphate) (CAS no: 65-30-5) at the dose concentration of 55 mg/kg bw. 50% mortality was observed. Hence, LD50 value was considered to be 55 mg/kg bw, when rats were treated with 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid via oral route.

The above experimental studies are supported with the study mentioned in publication and conducted on rats for the target chemical Nicotine sulphate to determine acute oral toxicity dose. The study was conducted in male Sprague-Dawley rats at the dose concentration of 75 (44-127) mg/kg bw. Single oral dose toxicity was usually determined by the method of Smyth et al. (1962) in which the LD50 and its 95% confidence limits are estimated by the moving average technique (Thompson, 1947; Weil, 1952). 50% mortality was observed. Hence, LD50 value was considered to be 75 mg/kg bw, with 95% confidence limits of 44-127 mg/kg bw, when male Sprague-Dawley rats were treated with 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid via oral route.

These studies are supported with the study available in publications and handbooks for the target chemical Nicotine sulphate. The acute oral toxicity study was conducted in 80 female Sherman strain rats at the dose concentration of 83 mg/kg bw. The given test chemical was dissolved as suspension in 95% ethyl alcohol and administered via oral gavage route. The survivors were held for daily observation until they appeared to have recovered completely or for a minimum of 14 days. Animals were died within 1hr to 4 days. Hence, LD50 value was considered to be 83 mg/kg bw, with 95% confidence limit of 75-91 mg/kg bw, when female Sherman strain rats were treated with 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid via oral gavage route.

All the above experimental studies are further supported with the study conducted on rats and mentioned in handbook, authoritative database and secondary literature at the dose concentration of 90 mg/kg bw. 50% mortality was observed. Hence, LD50 value was considered to be 90 mg/kg bw, when rats were treated with 3 -[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid via oral route.

The above experimental studies are contradicted with the studies conducted on mice. The studies are as follows –

The experimental study conducted on mice and mentioned in peer-reviewed journal and handbooks for the target chemical 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (Nicotine sulphate) (CAS no: 65-30-5).The acute oral toxicity study was conducted in mice at the dose concentration of 16 (12-21) mg/kg bw. 50% mortality was observed. Hence, LD50 value was considered to be16 mg/kg bw, with 95% confidence limit of 12-21 mg/kg bw, when mice were treated with 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid via oral route.

The above study is supported with the study conducted on mice and mentioned in authoritative databases and secondary sources for the target chemical 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (Nicotine sulphate) (CAS no: 65-30-5). The acute oral toxicity study was conducted in mice at the dose concentration of 8.55 mg/kg bw. Animals were observed for mortality and clinical signs.50% mortality was observed. Clinical signs such asdyspnea, behavioural changes, muscle contraction or spasticity, tremor were observed in treated mice. Hence, LD50 value was considered to be 8.55 mg/kg bw, when mice were treated with 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid via oral route.

From all the above experimental studies for the target chemical 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (Nicotine sulphate) (CAS no: 65-30-5), the LD50 value for rat is between 50-300 mg/kg bw and LD50 value for mice is between 5-50 mg/kg bw. As the rat is more preferable species for animal study than mice. Thus, comparing this value with the criteria of CLP regulation, Nicotine sulphate can be classified as “Category 3” for acute oral toxicity.

Justification for classification or non-classification

Based on the above experimental studies on 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (Nicotine sulphate) (CAS no: 65-30-5), it can be concluded that LD50 value is between 50-300 mg/kg bw, for acute oral toxicity. Thus, comparing this value with the criteria of CLP regulation, 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine; sulfuric acid (Nicotine sulphate) can be classified as “Category 3” for acute oral toxicity.