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EC number: 231-668-3 | CAS number: 7681-52-9
- 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: inhalation
Administrative data
- Endpoint:
- short-term repeated dose toxicity: inhalation
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- supporting study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: relevant supporting study to demonstrate data for Cl2 release for sodium hypochlorite
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 979
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
- Deviations:
- not specified
- Principles of method if other than guideline:
- No guideline indicated as study is a 6 weeks inhalation study. The conduct was similar to OECD guideline 412 "Repeated Dose Inhalation Toxicity: 28 day or 14 day Study".
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Chlorine
- EC Number:
- 231-959-5
- EC Name:
- Chlorine
- Cas Number:
- 7782-50-5
- Molecular formula:
- Cl2
- IUPAC Name:
- chlorine
- Details on test material:
- Chlorine gas
Chlorine and nitrogen mixture
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure:
- not specified
- Vehicle:
- other: no data
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 30 days (6 weeks)
- Frequency of treatment:
- 5 days/week, 6 h per day
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 1.0, 3.0 and 9.0 ppm
Basis:
nominal conc.
- Remarks:
- Doses / Concentrations:
1.0±0.04 ppm, 3.0±0.1 ppm, 8.99±0.45
Basis:
analytical conc.
- Control animals:
- other: air control group
- Details on study design:
- Post-exposure period: none
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):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Behaviour (functional findings):
- not specified
- 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:
- The results of this study indicated that unequivocal upper and lower respiratory tract change were produced in Fischer 344 rats exposed to 9 ppm of chlorine. This conclusion was supported by the clinical signs of generalised respiratory tract irritation, increased lung weights and lung to body weight ratios, and the histopathological changes which extended throughout the upper and lower respiratory tract of rats exposed to 9 ppm. The increases in the total number of segmented neutrophils at 9 ppm correlated very well with the inflammation and mucopurulent exudate of the upper and lower respiratory tract. The respiratory tract effects found in animals exposed to 3 or 1 ppm chlorine were very similar and much less severe than those seen at 9 ppm. Concentration-dependent elevations were seen in urine specific gravity at all exposure concentrations in females and 9 or 3 ppm in males. Blood urea nitrogen was raised in both sexes exposed to 9 ppm . The kidneys of both sexes were darkened in appearance and the histopathological examination of males exposed to 9 ppm showed swelling of the epithelial cells of the proximal convoluted tubules with increased eosinophilic cytoplasmic homogeneity and decreased granularity. The presence of renal effects was also supported by clinical observation of urinary staining and matting of the fur around the genitalia in both sexes exposed to 9 or 3 ppm chlorine. Evidence of hepatic effects were seen from elevations of the activity of several enzymes. A concentration-related increase in alkaline phosphates was seen in rats of both sexes exposed to 9 or 3 ppm. Additionally, gamma-glutamyl transpeptidase was elevated in both sexes exposed to 9 ppm and serum glutamic pyruvic transaminase was elevated in females at 9 ppm. Animals exposed to 9 ppm showed an increased hepatocellular cytoplasmic eosinophilic homogeneity. Furthermore, an increase in the degree of hepatocellular cytoplasmic vaculation was seen at 9 or 3 ppm. The spleen and thymus of rats exposed to 9 ppm showed a decreased content of lymphoid elements. This finding correlated with the statistically significant decreases in absolute and relative weights of these two organs at 9 ppm which may have been a function of the poor physical condition and decreased nutritional fate of these rats. Ulceration and oedema of the stomach wall was found in both sexes exposed to 9 ppm. A plausible explanation for this observation includes general stress or ingestion of hydrochloric and/or hypochlorous acids as a result of natural grooming or deposition in the oral cavity, either directly or via the mucus escalator.
Effect levels
- Dose descriptor:
- LOAEL
- Effect level:
- <= 3 mg/m³ air
- Sex:
- male/female
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The described observations indicated that repeated exposure of Fischer 344 rats to chlorine resulted in pulmonary effects at all level used, and hepatic and renal effects at 9 and 3 ppm chlorine. However, these results are difficult to interpret as they pertain to human exposures largely because of differences between rats and humans regarding pulmonary anatomy, patterns of respiration, and amount of pulmonary ventilation. A LO(A)EL of 1.0 ppm corresponding to 3.0 mg/m3 (0.806 mg/kg bw/d assuming a body weight of 320 g and a respiratory volume of 0.086 m3/6 h) but no NO(A)EL was found.
- Executive summary:
The results of this study indicated that unequivocal upper and lower respiratory tract change were produced in Fischer 344 rats exposed to 9 ppm of chlorine. This conclusion was supported by the clinical signs of generalised respiratory tract irritation, increased lung weights and lung to body weight ratios, and the histopathological changes which extended throughout the upper and lower respiratory tract of rats exposed to 9 ppm. The increases in the total number of segmented neutrophils at 9 ppm correlated very well with the inflammation and mucopurulent exudate of the upper and lower respiratory tract. The respiratory tract effects found in animals exposed to 3 or 1 ppm chlorine were very similar and much less severe than those seen at 9 ppm. Concentration-dependent elevations were seen in urine specific gravity at all exposure concentrations in females and 9 or 3 ppm in males. Blood urea nitrogen was raised in both sexes exposed to 9 ppm . The kidneys of both sexes were darkened in appearance and the histopathological examination of males exposed to 9 ppm showed swelling of the epithelial cells of the proximal convoluted tubules with increased eosinophilic cytoplasmic homogeneity and decreased granularity. The presence of renal effects was also supported by clinical observation of urinary staining and matting of the fur around the genitalia in both sexes exposed to 9 or 3 ppm chlorine. Evidence of hepatic effects were seen from elevations of the activity of several enzymes. A concentration-related increase in alkaline phosphates was seen in rats of both sexes exposed to 9 or 3 ppm. Additionally, gamma-glutamyl transpeptidase was elevated in both sexes exposed to 9 ppm and serum glutamic pyruvic transaminase was elevated in females at 9 ppm. Animals exposed to 9 ppm showed an increased hepatocellular cytoplasmic eosinophilic homogeneity. Furthermore, an increase in the degree of hepatocellular cytoplasmic vaculation was seen at 9 or 3 ppm. The spleen and thymus of rats exposed to 9 ppm showed a decreased content of lymphoid elements. This finding correlated with the statistically significant decreases in absolute and relative weights of these two organs at 9 ppm which may have been a function of the poor physical condition and decreased nutritional fate of these rats. Ulceration and oedema of the stomach wall was found in both sexes exposed to 9 ppm. A plausible explanation for this observation includes general stress or ingestion of hydrochloric and/or hypochlorous acids as a result of natural grooming or deposition in the oral cavity, either directly or via the mucus escalator.
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