Registration Dossier
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EC number: 231-836-6 | CAS number: 7758-19-2
- 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
Key value for chemical safety assessment
Effects on fertility
Description of key information
Chlorine dioxide and chlorite are characterized together for toxicity to reproduction because studies conducted with chlorite, the predominant degradation product of chlorine dioxide, are likely relevant to characterizing the toxicity of chlorine dioxide. In addition, studies conducted with chlorine dioxide may be relevant to characterizing the toxicity of chlorite. Chlorine dioxide is fairly unstable and rapidly dissociates, predominantly into chlorite and chloride, and to a lesser extent, chlorate. There is a ready interconversion among these species in water (before administration to animals) and in the gut (after ingestion). Therefore, what exists in water or the stomach is a mixture of these chemical species (i.e., chlorine dioxide, chlorite, chlorate) and possibly their reaction products with the gastrointestinal contents.
Key study: Experimental results: A two-generation reproduction and development neurotoxicity study with sodium chlorite in the rat was conducted according to EPA OPPTS 870.3800 (Reproduction and Fertility Effects). No evidence of reproductive toxicity.
Key study: Experimental results: One generation study with chlorine dioxide in the rat. No treatment-related effects were observed for parents in any dose groups. For F1 generation only the females showed any treatment-related changes: decreased vaginal weights in highest dose group.
Justification for selection of Effect on fertility via oral route:
Two-generation reproduction study with the test substance.
Link to relevant study records
- Endpoint:
- two-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study without detailed documentation
- Remarks:
- EPA guideline and GLP. The report is a summary of a much more detailed study and hence some of the individual results and observations are not reported.
- Qualifier:
- according to
- Guideline:
- EPA OPPTS 870.3800 (Reproduction and Fertility Effects)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- Source:Iffa Credo, BelgiumAge at study initiation: 6 weeks old
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Details on mating procedure:
- Mating ratio= 1:1
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Duration of exposure before mating:10 weeksDuration of exposure in general P, F1, F2 males, females:From beginning of the study until sacrifice of parent, F1, F2-generation
- Dose / conc.:
- 35 ppm
- Remarks:
- Equivalent to 4 and 5 mg/kg-bw/day in males and females respectively (sodium chlorite).Equivalent to 2.9 and 4 mg/kg-bw/day in male and female respectively (chlorite).Dose decreased 50 % (to 17.5 ppm) during lactation
- Dose / conc.:
- 70 ppm
- Remarks:
- Equivalent to 8 and 10 mg/kg-bw/day in males and females respectively (sodium chlorite).Equivalent to 6 and 7.5 mg/kg-bw/day in male and female respectively (chlorite).Dose decreased 50 % (to 35 ppm) during lactation
- Dose / conc.:
- 300 ppm
- Remarks:
- Equivalent to 30 and 39 mg/kg-bw/day in males and females respectively (sodium chlorite).Equivalent to 22 and 29 mg/kg-bw/day in male and female respectively (chlorite).Dose decreased 50 % (to 150 ppm) during lactation
- No. of animals per sex per dose:
- 30/sex/group for P generation25/sex/group for F1 generation
- Control animals:
- yes, concurrent vehicle
- Parental animals: Observations and examinations:
- CLINICAL OBSERVATIONS: YesBODY WEIGHT: Yes FOOD CONSUMPTION AND COMPOUND INTAKE: YesWATER CONSUMPTION AND COMPOUND INTAKE: Yes
- Oestrous cyclicity (parental animals):
- Yes
- Sperm parameters (parental animals):
- Parameters: Sperm motility, sperm morphology
- Litter observations:
- Parameters: Number and sex of pups, stillbirths, live births, presence of gross, anomalies, weight gain, physical or behavioural abnormalities OTHER EXAMINATIONS:Hematological and thyroid hormone data analysed from 1 pup/sex/dose from each F1 generation, followed by additional evaluations at 13 weeks for all F1 animals selected to rear the F2 generation.Red blood cell count (RBC), Hemoglobin levels (Hb), Hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentrations (MCHC), total white blood cell count (WBC), methemoglobin concentration (MetHb) and total serum T3 and T4 concentrations were evaluated.
- Postmortem examinations (parental animals):
- HISTOPATHOLOGY:Reproductive organs from animals in the high-dose and control groups or any animal with suspected reduced fertility.Organ tissue details not stated
- Postmortem examinations (offspring):
- HISTOPATHOLOGY:Reproductive organs from animals in the high-dose and control groups or any animal with suspected reduced fertility.Organ tissue details not stated
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- There were no effects in food consumption.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Dose-related decreases in water consumption were observed for males and females in the 70 and 300 ppm groups (ca. 25 % compared to control).Water consumption was ocassionally decreased in the 35 ppm group.
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related changes in estrous cyclicity or sperm motility and morphology.
- Reproductive function: sperm measures:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related changes in estrous cyclicity or sperm motility and morphology.
- Reproductive performance:
- not specified
- Description (incidence and severity):
- There were no treatment-related changes in mating, fertility, or gestational indices.
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 35 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- water consumption and compound intake
- Remarks on result:
- other: Dose-related decreases in water consumption were observed for males and females in the 70 and 300 ppm groups (ca. 25 % compared to control). Water consumption was ocassionally decreased in the 35 ppm group.
- Remarks:
- The effect was not accompanied by changes in body weight.
- Key result
- Critical effects observed:
- no
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Body weight and food consumption were significantly decreased at all measurement intervals for F1 males in the 300 ppm group ( ca 20% decreased) at most measurement intervals.Additionally, very small but statistically significant decreases in body weight were noted during the first 3-6weeks of the prebreed treatment period for F1 males in the 70 ppm group and F1 females in the 300 ppm group.During the last 7 days of gestation, at parturition and for varying lengths of time during lactation, body weights for F0 and F1 females in the 300 ppm group were decreased compared to females in the control group. The magnitude of the change in body weight from the control for dams in the 300 ppm treatment group generally was -4% to -6%.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- For F1 generation parental animals, dose-related decreases in water consumption were observed for males at all sodium chlorite treatment levels (ca. 10– 25% decreased) and for females in the 300 ppm group (ca. 20% decreased) at most measurement intervals.
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- For F1 adult animals (at week 13), small decreases in RBC count, Hb, HCT, MCV, MCH and WBC count and a small increase in MCHC was observed for male and/or female rats in the 300 ppm group. Very small but statistically significant changes in some of these endpoints also were observed for male and female animals in the 35 and 70 ppm groups.Finally, there were no treatment-related changes in the total serum concentrations of the thyroid hormones T3 or T4 for F1 PND 25 or F1 13-week-old animals.
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- A minor, albeit statistically significant, decrease in absolute brain weight (28%) was observed for male pups in the 300 ppm group sacrificed on PND 11 compared to the control. Decreased brain weight for these pups was associated with decreased pup weight at birth and a 14% decrease in pup weight on PND 11 compared to the control. Accordingly, brain weight to body weight ratios on PND 11 were increased for male pups in the 300 ppm group, although this increase (16%) was not statistically significantly different from the control. Decreases in absolute brain weight were not observed for female PND 11 pups, for male pups in the 35 and 70 ppm groups or for male or female PND 25 pups.
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related microscopic changes in reproductive tissues for male and female parental animals.Microscopic examination of the central and peripheral nervous system tissues for male and female PND 60 animals did not reveal any treatment-related alterations or pathology.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
- Description (incidence and severity):
- There were no gross or microscopic lesions noted in the brains or spinal cords of F1 PND 11 pups. In addition, there was no evidence of developmental changes, or anomalies in cell migration for PND 11 pups.
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related changes in estrous cyclicity.
- Reproductive function: sperm measures:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related changes in sperm motility and morphology.
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related changes in mating, fertility or gestational indices for F1 generation.
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 300 mg/L drinking water
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- haematology
- Remarks on result:
- other: Equivalent to 30 and 39 mg sodium chlorite/kg-bw/day in male and female rats respectively
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- > 300 mg/L drinking water
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- neuropathology
- Remarks on result:
- other: Equivalent to > 30 and > 39 mg sodium chlorite/kg-bw/day in male and female rats respectively
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 70 mg/L drinking water
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- haematology
- Remarks on result:
- other: Equivalent to 8 and 10 mg sodium chlorite/kg-bw/day in male and female rats respectively
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 300 mg/L drinking water
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- neuropathology
- Remarks on result:
- other: Equivalent to 30 and 39 mg sodium chlorite/kg-bw/day
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 300 mg/L drinking water
- System:
- haematopoietic
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not specified
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Treatment related decreases in body weight were observed for male and female pups in the 300 ppm treatment group from the F1,F2a and F2b generations. The magnitude of the change in pup body weight from control increased with age and ranged from 26% at birth to 210% on PND 24.The decreases were statistically significant from birth to weaning for F1 pups and during the final 2–3 weeks of lactation for F2a and F2b pups
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related changes in the number of pups born, the pup gender ratio, live birth index or pup survival indices, nor were there differences in ano–genital distance or gross external alterations for pups . There were no clear treatment-related changes in pup developmental indices, including ear and eye opening, righting reflex, auditory startle response and pupil response.
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not specified
- Histopathological findings:
- not specified
- Other effects:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related changes in the number of pups born, the pup gender ratio, live birth index or pup survival indices, nor were there differences in ano–genital distance or gross external alterations for pups (data not shown). There were no clear treatment-related changes in pup developmental indices, including ear and eye opening, righting reflex, auditory startle response and pupil response.
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- other: F1 and F2 generations
- Effect level:
- 35 mg/L drinking water
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: See remarks:
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- other: F1 and F2 generations
- Effect level:
- 2.9 other: mg sodium chlorite/kg-bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: See remarks
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 70 mg/kg bw (total dose)
- Organ:
- brain
- liver
- Treatment related:
- yes
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- No evidence of reproductive toxicity. Based on the results of this study the NOEL for effects on reproduction and thyroid hormones is 300 ppm. The NOAELs for hematological toxicity and neurotoxicity are considered to be 70 and 300 ppm, respectively. These NOAELs are equivalent to approximately 8 and 30 mg sodium clorite/kg-bw/day, respectively, for males and approximately 10 and 39 mg sodium clorite/kg-bw/day , respectively, for females.
- Executive summary:
A two-generation reproduction and development neurotoxicity study with sodium chlorite in the rat was conducted according to EPA OPPTS 870.3800 (Reproduction and Fertility Effects). No evidence of reproductive toxicity was observed. Sodium chlorite resulted in a decrease in the water consumption in all groups and food consumption and body weights in 70 and 300 ppm groups. Pup body weights were decreased in the 300 ppm group and small delays were observed in times to preputial separation and vaginal opening. Mild anaemia and mild methemoglobinemia were observed for animals in the 300 ppm group. Thyroid hormone levels were not affected by the treatment. Changes to the nervous system were limited to small decreases in amplitude of auditory startle responses for post natal day 25 pups in the 70 and 300 ppm groups of questionable neurotoxicological significance.
Reference
The F1 generation is the second parent generation. Details on the results can be found in Results P1 (Second parent generation).
Table A6_8_2(2)-2 Table for reproductive toxicity study |
| ||||||||||
Parameter | control | low dose | medium dose | High dose | |||||||
Generation | m | f | m | f | m | f | m | f | |||
Mortality | Incidences of significance | P | - | - | - | - | - | - | - | - | |
F1 | - | - | - | - | - | - | - | - | |||
Food consumption | Change relative to control | P | - | - | - | - | - | - | - | - | |
F1 | ↓ | ||||||||||
Water consumption | % decrease relative to control | P | - | - | - | - | 10 - 25 % decrease | ||||
F1 | - | - | 10-25 | - | 10-25 | - | 10-25 | 20 | |||
Body weight gain | Change relative to control | P | - | - | - | - | - | - | - | - | |
F1 | ↓ | ↓ | ↓ | ||||||||
F2a/b | ↓ | ||||||||||
Clinical Observations | Incidences of significance | P/F1 | - | - | - | - | - | - | - | - | |
Organ weights | % of control | ||||||||||
Histopathologic examination | Incidence | All | - | - | - | - | - | - | - | - | |
Hematological examination: | Significant changes vs control | ||||||||||
RBC, Hb, HCT, MCV, MCH, MCHC | F1 | ↓ | ↓ | ||||||||
WBC | F1 | ↓ | ↓ | ↓ | ↓ | ||||||
MetHb | F1 | ↑ | ↑ | ↑ | ↑ | ||||||
T3 and T4 | F1 | - | - | - | - | - | - | - | - | ||
Reproductive Performance | Significant changes vs control | ||||||||||
Mating index | All | - | - | - | - | - | - | - | - | ||
Fertility index | All | - | - | - | - | - | - | - | - | ||
Birth index | All | - | - | - | - | - | - | - | - | ||
Live birth index | All | - | - | - | - | - | - | - | - | ||
Gestation index | All | - | - | - | - | - | - | - | - | ||
Sex ratio | All | - | - | - | - | - | - | - | - | ||
Survival index | All | - | - | - | - | - | - | - | - | ||
Sperm characterization | P/F1 | - | - | - | - | - | - | - | - | ||
Deformations | Significant changes vs control | All | - | - | - | - | - | - | - | - | |
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 2.9 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Klimisch 2. EPA guideline and GLP.
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Description of key information
Key study experimental results: Study perfomed in rabbit according to EPA OPP 83-3 (Prenatal Developmental Toxicity Study). Oral administration of sodium chlorite during organogenesis at 600 and 1200 ppm elicited dose related reductions in maternal water with consequent reductions in maternal food consumption, production of faecal pellets and body weight gain. Despite the maternal effects there was no evidence of embryo-lethality or teratogenicity.
There are additional studies in a second specie, i.e. rat.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to
- Guideline:
- EPA OPP 83-3 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals and environmental conditions:
- Source:Interfauna UK Ltd., Huntington, Cambs., UKAge/weight at study initiation:Age: 4 – 5 months oldWeight: 3.05 – 4.00 kg (at mating)
- Route of administration:
- oral: drinking water
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Mating period: Timed mated at start of study, mating period not stated.
- Duration of treatment / exposure:
- Duration of treatment: Days 7-19 (post mating)Post exposure period: 9 days
- Dose / conc.:
- 200 mg/L drinking water
- Remarks:
- 12.2 mg sodium chlorite/kg-bw/day or 9 mg chlorite/kg-bw/day
- Dose / conc.:
- 600 mg/L drinking water
- Remarks:
- 36.6 mg sodium chlorite/kg-bw/day or 27 mg chlorite/kg-bw/day
- Dose / conc.:
- 1 200 mg/L drinking water
- Remarks:
- 58.7 mg sodium chlorite/kg-bw/day or 44 mg chlorite/kg-bw/day
- No. of animals per sex per dose:
- 16 or 17
- Control animals:
- yes, concurrent vehicle
- Maternal examinations:
- CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily from day 3 of pregnancy. The appearance time, degree and continuance of clinical signs were noted.
BODY WEIGHT: Yes
- Time schedule for examinations: Weighed on day 0 of pregnancy at the supplier’s premises. Bodyweights were recorded daily from day3 to day 22 and on days 25 and 28 of pregnancy.
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- The amount of food was recorded every 2 days from day 3 to day 27 and over 1 day from day 27 to day 28 of pregnancy.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes Water consumption was measured daily from day 3 to day 22 of pregnancy by weighing each water bottle after filling and weighing again 24 h later. During the dosing period (days 7 to 19 of pregnancy) residue drinking water formulations were discarded and replaced with fresh formulations daily. - Ovaries and uterine content:
- Gravid uterine weightNumber of corpora luteaNumber and distribution of implantation sites. The implantations were classified as early or late resorptions.
- Fetal examinations:
- GENERALNr. of live foetuses, nr. of dead foetuses, foetal weight, external abnormalities
.SKELETALThe bones were identified and examined for normality with respect to shape, size and the extent of ossification.
SOFT TISSUEFoetuses were briefly fixed in alcohol prior to being skinned and dissected. The brain, eyes, palate and major organs and blood vessels in the thorax and abdomen were examined. The sex of the foetuses, as assessed from the appearance of the internal genitalia were recorded. - Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- The only treatment – related observation was a dose – related reduction in the production of faecal pellets, which was associated with reductions in food consumption.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Description (incidence):
- There were no treatment related mortalities There were no treatment related mortalities.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Transient reductions in body weight gain were observed at 600 and 1200 ppm at the onset of dosing. The differences from the controls were statistically significant at 1200 ppm. At 200 ppm there were no difference from controls in bodyweight gain.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Statistically significant dose-related reduction in food consumption were observed at the onset at 600 and 1200 ppm. There were no treatment-related reductions in food consumption at 200 ppm.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- There was a dose-related effect of treatment on water consumption at 600 and 1200 ppm. At the onset of dosing, water consumption was reduced by over 50% at 1200 ppm and by 20 – 30% at 600 ppm. The differences were statistically significant. There was considered to be no effect of treatment on water consumption at 200 ppm.
- Ophthalmological findings:
- not examined
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related abnormalities observed macroscopically at necropsy.
- Neuropathological findings:
- not examined
- Other effects:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- Mean numbers of corpora lutea, implantations and live foetuses were similar in all groups and there was no adverse effect of treatment on post-implantation losses.
- Dose descriptor:
- LOAEL
- Effect level:
- 600 mg/L drinking water
- Basis for effect level:
- other: maternal toxicity
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 36 other: mg sodium chlorite/kg bw/day
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 27 other: mg chlorite/kg bw/day
- Based on:
- act. ingr.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/L drinking water
- Basis for effect level:
- other: maternal toxicity
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 12 other: mg sodium chlorite/kg bw/day
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 9 other: mg chlorite/kg bw/day
- Based on:
- act. ingr.
- Basis for effect level:
- other: maternal toxicity
- Key result
- Abnormalities:
- no effects observed
- Description (incidence and severity):
- Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Field "Description (incidence and severity)" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.DescriptionIncidenceAndSeverityFetalPupBodyWeightChanges): Mean foetal weight was slightly lower at 600 and 1200 ppm than in the control group, although this could not be definitely attributed to treatment. Mean foetal weight was similar to the control group at 200 ppm. - Changes in sex ratio:
- no effects observed
- Description (incidence and severity):
- The sex ratio of the live foetuses was similar in all groups.
- External malformations:
- no effects observed
- Description (incidence and severity):
- There was no evidence of teratogenicity at any dose level.
- Skeletal malformations:
- not specified
- Description (incidence and severity):
- There was no evidence of teratogenicity at any dose level. At 600 and 1200 ppm there were slightly higher incidences of foetuses with retardation of ossification of some bones, than in the control group. This was not unexpected as there were lower mean foetal weights in these groups.
- Other effects:
- no effects observed
- Description (incidence and severity):
- There was no evidence of teratogenicity at any dose level.
- Dose descriptor:
- LOAEL
- Effect level:
- 600 mg/L drinking water
- Basis for effect level:
- other: embryotoxicity
- Key result
- Dose descriptor:
- LOAEL
- Effect level:
- 36 other: mg sodium chlorite/kg bw/day
- Basis for effect level:
- other: embryotoxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 27 other: mg chlorite/kg bw/day
- Based on:
- act. ingr.
- Basis for effect level:
- other: embryotoxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/L drinking water
- Basis for effect level:
- other: embryotoxicity
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 12 other: mg sodium chlorite/kg bw/day
- Basis for effect level:
- other: embryotoxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 9 other: mg chlorite/kg bw/day
- Based on:
- act. ingr.
- Basis for effect level:
- other: embryotoxicity
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- not specified
- Conclusions:
- Oral administration of sodium chlorite during organogenesis in the rabbit at 600 and 1200 ppm elicited dose related reductions in maternal water with consequent reductions in maternal food consumption, production of faecal pellets and body weight gain. Despite the maternal effects there was no evidence of embryo-lethality or teratogenicity. There was an indication of embryonic growth retardation but this was only slight, was not dose-related and could not conclusively be related to treatment. There was considered to be no effect of treatment on the mothers or on embryonic development at 200 ppm.
- Executive summary:
The aim of the study was to determine the toxicity of the test material on the development of the rats.
The test procedure was: EPA OPP 83-3 (Prenatal Developmental Toxicity Study).
The test concentrations were: 0, 200, 600 and 1200 mg/L (0, 12.2, 36.6 and 58.7 mg sodium chlorite/kg/day or 0, 9, 27 and 44 mg chlorite/kg/day). Oral administration of sodium chlorite during organogenesis in the rabbit at 600 and 1200 ppm elicited dose related reductions in maternal water with consequent reductions in maternal food consumption, production of faecal pellets and body weight gain. Despite the maternal effects there was no evidence of embryo-lethality or teratogenicity. There was an indication of embryonic growth retardation but this was only slight, was not dose-related and could not conclusively be related to treatment. There was considered to be no effect of treatment on the mothers or on embryonic development at 200 ppm.
Reference
Table A6_8_1(2)-1. Table for Teratogenic effects: Maternal effects | |||||||||||||||||
Parameter | Control data | 200 ppm | 600 ppm | 1200 ppm | dose-response | ||||||||||||
historical | study | ||||||||||||||||
Number of dams examined | N/Aa | 16 | 17 | 17 | 16 | ||||||||||||
Clinical findings during application of test substance | N/A | N/Sb | N/S | N/S | N/S | ||||||||||||
Mortality of dams (%) | N/A | 1 (0.16)* | 0 | 1 (0.16)* | 0 | ||||||||||||
Abortions | N/A | N/S | N/S | N/S | N/S | ||||||||||||
Body weight gain | N/A | Days 7 – 11 of pregnancy: transient loss | |||||||||||||||
Food consumption | N/A | Days 7 – 11 of pregnancy: transient decrease | |||||||||||||||
Water consumption | N/A | Significantly lower | Significantly lower | ||||||||||||||
Pregnancies | N/A | 13 | 13 | 12 | 14 | ||||||||||||
Necropsy findings in dams dead before end of test | N/A | N/A | N/A | N/A | N/A | N/A | |||||||||||
* Sacrificed in extremis – their condition was considered to be incidental and unrelated to sodium chlorite treatment a N/A = not applicable b N/S = not specified | |||||||||||||||||
Table A6_8_1(2)-2. Table for Teratogenic effects: Litter response (caesarean section data) | |||||||||||||||||
Parameter | Control data | 200 ppm | 600 ppm | 1200 ppm | dose-response | ||||||||||||
historical | study | ||||||||||||||||
Corpora lutea (Mean no. ± S.D) | N/A | 11.9 ± 2.3 | 11.9 ± 1.9 | 12.8 ± 2.3 | 12.1 ± 2.7 | ||||||||||||
Implantations (Mean no. ± S.D) | N/A | 10.7 ± 2.2 | 10.8 ± 1.8 | 10.7 ± 2.4 | 10.1 ± 2.2 | ||||||||||||
Total number of foetuses | N/A | 111 | 125 | 108 | 124 | ||||||||||||
Mean number of live foetuses | N/A | 8.5 ± 2.9 | 9.6 ± 1.9 | 9.0 ± 2.6 | 8.9 ± 2.4 | ||||||||||||
Pre-implantation loss (%) | N/A | 10.4 | 8.4 | 16.1 | 14.9 | ||||||||||||
Post-implantation loss (%) | N/A | 21.3 | 11.1 | 15.4 | 12.6 | ||||||||||||
Foetus weight (group mean) [g] | N/A | 35 ± 4.2 | 35.8 ± 3.7 | 33.1 ± 2.6 | 33.2 ± 3.1 | ||||||||||||
Foetal sex ratio [ratio m/f] | N/A | 55:45 | 41:59 | 48:52 | 52:48 | ||||||||||||
| |||||||||||||||||
Table A6_8_1(2)-3. Table for Teratogenic effects examination of the foetuses | |||||||||||||||||
Parameter | Control data | 200 ppm | 600 ppm | 1200 ppm | dose-response | ||||||||||||
historical | Study | ||||||||||||||||
External and visceral malformations* [%] | N/A | 28.6 | 22.8 | 32.3 | 26.8 | ||||||||||||
External and visceral anomalies* [%] | N/A | 1.5 | 0.5 | 6.6 | 2.6 | ||||||||||||
Skeletal malformations* [%] | N/A | 0.0 | 0.8 | 5.4 | 0.0 | ||||||||||||
Skeletal anomalies* [%] | N/A | 7.7 | 6.3 | 14.2 | 13.9 | ||||||||||||
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 9 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rabbit
- Quality of whole database:
- Klimisch 1. This study was carried out in accordance with internationally valid GLP principles.
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Chlorine dioxide and chlorite are characterized together for toxicity to reproduction because studies conducted with chlorite, the predominant degradation product of chlorine dioxide, are likely relevant to characterizing the toxicity of chlorine dioxide. In addition, studies conducted with chlorine dioxide may be relevant to characterizing the toxicity of chlorite. Chlorine dioxide is fairly unstable and rapidly dissociates, predominantly into chlorite and chloride, and to a lesser extent, chlorate. There is a ready interconversion among these species in water (before administration to animals) and in the gut (after ingestion). Therefore, what exists in water or the stomach is a mixture of these chemical species (i.e., chlorine dioxide, chlorite, chlorate) and possibly their reaction products with the gastrointestinal contents.
Key study: Experimental results: The test procedure was: EPA OPP 83-3 (Prenatal Developmental Toxicity Study). Oral administration of sodium chlorite during organogenesis in the rabbit at 600 and 1200 ppm elicited dose related reductions in maternal water with consequent reductions in maternal food consumption, production of faecal pellets and body weight gain. Despite the maternal effects there was no evidence of embryo-lethality or teratogenicity. There was an indication of embryonic growth retardation but this was only slight, was not dose-related and could not conclusively be related to treatment.
Justification for selection of Effect on developmental toxicity: via oral route:
Highest quality study (Klimish score =1) on developmental toxicity.
Justification for classification or non-classification
Based on the available data on effects on fertility and developmental toxicity, the substance is not classified according to the CLP Regulation (EC) no. 1272/2008.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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