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EC number: 225-059-1 | CAS number: 4635-59-0
- 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
Endpoint summary
Administrative data
Description of key information
Rats exposed to 0.002, 0.012, and 0.059 mg/l 4-chlorobutyryl chloride for 4 weeks (6hrs/day, 5days/week) by inhalation showed clinical symptoms linked to respiratory tract inflammation/ irritation (TNO, 1996). Growth retardation, changes in blood parameters clinical chemistry, and organ weights (liver, kidney, spleen, and lung, adrenals) are predominantly noted at the high dose level and can be explained to be secondary due to severe effects on the respiratory tract. They were noted in a dose-related manner, regarding both severity and localization. The entire respiratory tract was severely affected in all high-dose animals, whereas only very slight effects on the transitional and respiratory epithelium were in animals exposed to the lowest dose of 0.002 mg/l, which may be regarded as a lowest observed adverse effect level (LOAEL). Based on histology findings, there was no other target organ than the respiratory tract in concentrations up to 0.059 mg/L.
Key value for chemical safety assessment
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Dose descriptor:
- LOAEC
- 2 mg/m³
- Study duration:
- subacute
- Species:
- rat
Additional information
In an OECD TG 412 study with supporting substance CCl2, groups of 5 Wistar rats/sex were exposed by inhalation to 0, 2.1, 11.8, and 59.1 mg/m³ (0, 0.002, 0.012, and 0.059 mg/L) as a vapor for 6 h/d, 5 d/week for 4 weeks (20 exposures days for males and 21 for females) (TNO, 1996).
There were no deaths and clinical signs were limited to sniffing in all high-dose rats during the last week of exposure and in a few rats of the mid-dose group. Statistically significant decreased body weights were observed in both high-dose and mid-dose (males only) groups.
Statistically significant increases in red blood cells, hemoglobin and packed cell volume were observed in high dose males; similar but less pronounced effects were noted in females (only packed cell volume and red blood cells reached a level of significance). The differential white blood cell count revealed statistically significantly increased absolute and relative numbers of neutrophils and decreased absolute and relative numbers of lymphocytes in the high-dose groups. There were no test substance related clinical chemistry changes.
Statistically significant relative organ weight increases were noted for adrenals, kidneys, and lungs in both high-dose groups; only the relative kidney weight was increased in the mid-dose group. Absolute weight increases were noted for adrenals (females only) and lungs (increase), and liver and spleen (decrease) in the high dose group.decrease) in the high dose group. Small testes, either unilateral or bilateral, were noted in 4 males, one from each group including the control group. Since this finding was seen in all groups, this finding was not considered to be treatment-related. Swollen lungs were observed in all high-dose animals and in 5 mid-dose animals.
Microscopic changes were noted in the nasal cavity for low dose rats; in the nasal cavity, larynx and trachea for mid-dose rats; and in the entire respiratory tract for high-dose rats. The effects (severity, localization, extension) in the nasal cavity depended on the dose level. In low-dose animals, it was described as very slight to slight squamous metaplasia and hyperplasia of the transitional epithelium, and very slight focal hyperplasia of the respiratory epithelium. In mid-dose animals, the localization of effects on the transitional epithelium was comparable to that seen in low-dose rats; the severity ranged from slight to moderate. The transitional epithelium was almost entirely hyperplasic and included mucous cell hyperplasia. Very slight to slight suppurative rhinitis was seen. In high-dose rats, almost the entire transitional and ciliate respiratory lining of the nasal cavity was affected by squamous metaplasia, hyperplasia, and suppurative rhinitis, which included focal intraepithelial microabcesses and focal epithelial erosion. Epithelial hyperplasia was seen in the larynx of 9 high-dose and 3 mid-dose rats. Occasionally, very slight inflammatory cell infiltrates, epithelial erosion and intraluminal cell debris with mucous were observed. Focal hyperplasia predominated in mid-dose animals; a more diffuse, disorganized atypical hyperplasia was mainly noted in high-dose rats. Epithelial hyperplasia of the trachea and extrapulmonary bronchi was found in animals of the mid- and high-dose groups. The lesion progressed from focal, organized hyperplasia with mucous cell hyperplasia mainly in mid-dose rats to diffuse, more disorganized, atypical hyperplasia mainly in high-dose animals. Microscopic changes in lungs were seen in high-dose rats only. The lesions consisted of epithelial hyperplasia lining the bronchi/bronchioli, an increased number of polymorphonuclear cells around blood vessels and bronchi/bronchioli, perivascular edema and an increase in size and activation of peribronchial/peribronchiolar lymphoid tissue. The epithelial hyperplasia ranged from an atypical hyperplasia in the upper bronchi to mucous cell hyperplasia in the lower bronchi/bronchioli. No lesions were observed in the epithelium of the terminal bronchioli.
The entire respiratory tract was severely affected in all high-dose animals, whereas only very slight effects on the transitional and respiratory epithelium were observed in animals exposed to the lowest dose of 0.002 mg/L, which may be regarded as a lowest observed adverse effect level (LOAEL).
Based on histology findings, there was no other target organ than the respiratory tract in concentrations up to 0.059 mg/L.
Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: larynx; respiratory: lung; respiratory: nose; respiratory: trachea
Justification for classification or non-classification
No classification concerning repeated dose toxicity is warranted according to EU Regulation 67/548 and EU Regulation 1272/2008 as classification criteria are not met.
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