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EC number: 236-671-3 | CAS number: 13463-41-7
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- chronic toxicity: oral
- Remarks:
- combined repeated dose and carcinogenicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 004
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- GLP compliance:
- yes
Test material
- Reference substance name:
- Pyridine-2-thiol 1-oxide, sodium salt
- EC Number:
- 223-296-5
- EC Name:
- Pyridine-2-thiol 1-oxide, sodium salt
- Cas Number:
- 3811-73-2
- Details on test material:
- - Analytical purity: 40.8%
- Lot/batch No.: 99072150
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Nossan Srl
- Age at study initiation: 27-29 days
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Duration of treatment / exposure:
- 104 weeks (except low dose males, which were sacrificed during week 98)
- Frequency of treatment:
- Daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 0.5, 1.4, 4.0/2.8/2.1 mg a.s. / kg bw. High dose was reduced from 4.0 mg a.s. / kg bw to 2.8 mg a.s. / kg bw from week 7 onwards due to severe toxicity. High dose was further reduced to 2.1 mg a.s. / kg bw for females after 9 months of treatment
Basis:
- No. of animals per sex per dose:
- -Main group: 56
-Control, low dose, medium dose: 12
-High dose: 20
-Veterinary control: 16
Examinations
- Observations and examinations performed and frequency:
- -Bodyweight
-Food consumption
-Water consumption
-Clinical signs
-Behaviour
-Palpation
-Ophthalmic examination
-Haematology:
Number of animals: 20 animals/sex/group
Time points: After 3, 6, 12, 18, 24 months of treatment
Parameters: Haematocrit, haemoglobin concentration, erythrocyte count, reticulocyte count, MCV, MCH, MCHC, total and differential leukocyte count, platelet count, prothrombin time
-Clinical chemistry:
Number of animals: 10 animals/sex/group
Time points: After 6, 12, 18, 23 months of treatment
Parameters: alkaline phosphatase, alanine aminotransferase, aspartate amino¬transferase, urea, creatinine, glucose, albumin, total bilirubin, total cholesterol, total protein, sodium, potassium, calcium, chloride.
Other Determination of acetylcholinesterase of surviving animals of the high dosed and the control satellite groups.
-Urinalysis:
Number of animals: 10 animals/sex/group
Time points: After 3, 6, 12, 18, 24 months of treatment
Parameters: Appearance, volume, specific gravity, pH, protein, glucose, blood, ketones, bilirubin.
Other Microscopic examination of the sediment. - Sacrifice and pathology:
- -Organ weights: adrenals, brain, epididymides, heart, liver, kidneys, ovaries, spleen, testes, uterus
-Histopathology: adrenals, aorta, bone marrow, brain, caecum, colon, duodenum, epididymides, eyes, Harderian gland, heart, ileum, jejunum, kidneys, larynx, liver, lungs, lymph nodes – cervical and mesenteric, mammary area, nasal cavity, nasopharynx, oesophagus, optic nerves, ovaries, pancreas, paranasal sinuses, parathyroid, pharynx, pituitary, prostate, rectum, salivary glands, sciatic nerve, seminal vesicle, skeletal muscle, skin, spinal cord, spleen, sternum, stomach, testes, thyroid, trachea, urinary bladder, uterus. - Statistics:
- Continuous variables: analysis of variance followed by Dunnett's test.
Tumour incidence: Fishers exact test.
Histopathology findings: non-parametric Kolmogorov-Smirnov test
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Details on results:
- -Mortality: Control: 1 female in week 29.
Low dose: 2 females (week 21 and 45).
Mid dose: 1 male (week 52) and 1 female (week 43)
High dose: 1 male (week 49) and 3 females (weeks 6, 26, 37)
-Body weight: A significant lower body weight was observed in the high dosed males and females, compared to the control. The body weight gain was also significantly lower in the mid dosed females.
-Clinical signs: Some toxic signs as ataxia, motility impairment, emaciation, etc. were noted in few animals of the mid dosed group and in the high dosed group in few males and most females.
-Motor activity: An increase in locomotor activity was noted in high dosed animals, compared to the control
-Reactivity to stimuli: A significant decrease in landing foot splay was noted in mid- and high-dosed animals
-Macroscopic post mortem: Decedents:Possibly treatment-related findings were: reduced size of skeletal muscle and thickness of the sciatic nerve.
Terminals:Thickness of the sciatic nerve and reduced size of skeletal muscle were mainly noted in high dosed females.
-Organ weights: No effects in males. Females: significant decrease of the heart weight in high dosed animals, compared to the control.
-Histopathology: Decedents: Skeletal muscle: mild to moderate myofiber degeneration, necrosis and atrophy, in one case also adipose tissue replacement and focal inflammation, in high dosed animals. Lower degree of findings in the mid dosed female.
Terminals: Skeletal muscle and sciatic nerve were the main targets:
Skeletal muscle: slight to marked myofiber degeneration, necrosis and atrophy, and slight to moderate adipose tissue replacement of myofibers were reported in males and females of the mid- and high-dosed groups, with a dose-related trend. Inflammatory cell infiltrations were observed in high dosed animals of both sexes.
Sciatic nerve: slight to moderate fibre degeneration in 5/17 high dosed females. Mild degree of this change was reported in single males from the mid- and high-dose groups and in a mid-dose female.
Other organs: Findings such as bile duct proliferation in livers or neoplastic lesions were considered of no or minor relevance.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 0.5 mg/kg bw/day (nominal)
- Sex:
- male/female
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Peripheral nervous tissue (the sciatic nerve was investigated histopathologically) and skeletal muscle are the main targets of toxic action and related clinical signs such as ataxia, necropsy findings and histological changes were found in the 3 dosed groups in both sexes in a dose-related expression. The NOAEL is 0.5 mg/kg body weight per day for the 12 months toxicity study. This information may not be used for any purpose other than in support of the Chemical safety Report submitted by Arch Chemicals Inc. under Regulation EC 1907/2006.
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.
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