Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Acute Oral toxicity on Chlorine dioxide at 0.2%: LD50 combined: 94 mg/kg bw (K, Reliability 1).

Acute Dermal toxicity: not applicable as Chlorine dioxide is classified as corrosive.

Acute Inhalation toxicity:

- Gas: LC50 combined = 89,6 mg/m3 = 32 ppm (K, Reliability 1)

- Solution at 0,6 %: LC50 combined = 6.83 mg 0.6% ClO2 solution/L air/4h as pure ClO2 = 6830 mg/m3 (K, Reliability 2)

 

  Acute Oral toxicity Acute Dermal toxicity Acute Inhalation toxicity
Chlorine dioxide Gas1 NC N/A

Acute Tox. 1 (H330: Fatal if inhaled)

Chloride dioxide [0.5-0.82 %[ aqueous solution

Acute Tox. 3* (H301: Toxic if swallowed)²

N/A

NC3

Chloride dioxide [0.82-1 %[ aqueous solution

Acute Tox. 3* (H301: Toxic if swallowed)²

N/A

Acute Tox. 4 (H332: Harmful if inhaled)3

Chloride dioxide [1-2 %[ aqueous solution

Acute Tox. 3* (H301: Toxic if swallowed)²

N/A

Acute Tox. 4 (H332: Harmful if inhaled)3

1Classification of gas form is provided for information purpose only, as the registered reference substance; but the substance will actually be used only as aqueous solutions generated in situ.

² Existing harmonised classification (Index N°017-026-01-0), as Acute Tox. 3 * considered as a minimum classification in the harmonised entry, no more severe level was identified based on available data.

3According to the study result (Haferkorn, 2012), and applying the classification criteria for acute inhalation toxicity (5 mg/L for mist/aerosol), chlorine dioxide solutions have to be classified as category 4 for acute inhalation toxicity (ATI4) above a concentration limit of 0.82%, based on prorata of concentration according to CLP Regulation (EC) 1272/2008 (6.83 mg/L x 0.6% / 5 mg/L).

NC = Not classified

N/A: not applicable as Chlorine dioxide is classified as corrosive.

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:
key study
Study period:
1995-03-15 to 1995-04-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Italia
- Age at study initiation: 7-9 weeks on receipt
- Weight at study initiation: on receipt: males 225-250 g, females 200-225 g
- Housing: 5 animals/sex/cage
- Diet: GLP 4RF21 top certificate pelleted diet produced by Charles River ad libitum
- Water: from the municipal water main system filtered and distributed ad libitum
- Acclimation period: 5 days, daily observation

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2 °C
- Humidity: 55 +/- 10 %
- Air changes: about 20/hour filterd on HEPA 99.97 %
- Photoperiod: 12 hrs dark / 12 hrs light
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Total volume of test material applied: 10, 20 and 40 mL/kg b.w.
Doses:
Dose levels: 20, 40 and 80 mg/kg b.w.
No. of animals per sex per dose:
Number of animals per group 10 animals: 5/sex/group
Control animals:
no
Details on study design:
No additional data
Statistics:
No data
Preliminary study:
No data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
93.86 mg/kg bw
Based on:
test mat.
95% CL:
45.52 - 193.53
Remarks on result:
other: The LD50 was a calculated value.
Mortality:
Death occurred in 2 males and 2 females treated at 80 mg/kg and in 2 males treated at 40 mg/kg within 24 – 48 hours after the test article administration. No 20 mg/kg treated rats died.
Clinical signs:
other: Animals treated at the lowest dose (20 mg/kg b.w.) clinically showed hypoactivity, piloerection and hunched posture during the first three days of the study and then recovered. Females treated at 40 mg/kg showed the same clinical signs up to day 5 of the
Gross pathology:
The autopsy of animals which died during the study showed test article-related changes in the gastrointestinal tract: congestion and erosions with mucus or test article presence in the stomach and meteorism and thinning walls with catarrhal or catarrhal-hemorrhagic content in the intestine. Congestion of the lungs, of the kidneys and of the liver (with sporadic case of congestion of the thymus, of the retropharyngeal lymph nodes and of the spleen) and decreased size of the spleen were also observed and considered as agonal or post-mortem findings.
Animals treated at 20 mg/kg (lowest dose) did not show any necroscopic changes at the autopsy performed at the end of the study. At the autopsy of the surviving animals belonging to the groups treated with the highest doses (40 and 80 mg/kg) changes in the stomach were observed. These changes consisted of thickening of the glandular mucosa and were considered test article related.
Other findings:
No other findings

Table 7.2.1/1: Table for Acute Toxicity

Dose (mg/kg)

Number of dead /
number of investigated

Time of death (range)

Observations

0

N/A

N/A

N/A

20

0/10

N/A

N/A

40

2/10

day 1 (1 animal) day 2 (1 animal)

Two male animals

80

4/10

day 2 (3 animals)
day 3 (1 animal)

Two female, two male animals

LD50 value

93.86 (95% C.L. = 45.52 – 193.53)

 

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Under the test conditions, oral LD50 Combined Males/Females = 93.86 mg/kg b.w..(95% C.L of 45.52 – 193.53 mg/kg). Therefore, Chlorine dioxide at 0.2% is classified Category 3 (H301: Toxic if swallowed) according to the CLP regulation (1272/2008) and to the GHS, as the LD50 value is comprised between 50 and 300 mg/kg bw.
Executive summary:

In an acute toxicity study conducted according to the OECD guideline No. 401 and in compliance with GLP, Sprague-Dawley rats were administered Chlorine Dioxine (as a 0.2 % solution in water) by gavage at doses of 20, 40 and 80 mg/kg bw. Animals were then observed for 7 days for mortality, body weight changes. Gross autopsy was performed at the end of the experiment.


 


Death occurred in 2 males and 2 females treated at 80 mg/kg b.w. and in 2 males treated at 40 mg/kg b.w. within 24 -48 hours after the test substance administration. No rat died in the 20 mg/kg b.w. group.


Oral LD50combined = 93.86 mg/kg bw (95% C.L. of 45.52 -193.53 mg/kg bw).


Animals treated at the lowest dose (20 mg/kg b.w.) clinically showed hypoactivity, piloerection and hunched posture during the first three days of the study and then recovered.


Females treated at 40 mg/kg bw showed the same clinical signs up to day 5 of the study. Males treated at 40 mg/kg bw and all animals treated at the highest dose (80 mg/kg bw) showed clinical signs involving the CNS, the respiratory tract, and also piloerectoin, hunched posture and salivation. All reviving animals recovered within days 4 -7 of the study.


 


The autopsy of animals which died during the study showed test substance-related changes in the gastrointestinal tract: congestion and erosions with mucus or test substance presence in the stomach and thinning walls with catarrhal or catarrhal-hemorrhagic content in the intestine. Congestion of the lungs, of the kidneys and of the liver and decreased size of the spleen were also observed. Animals treated at 20 mg/kg bw didn't show any necroscopic changes at the autopsy performed at the end of the study.


The surviving animals belonging to the groups treated with the highest doses (40 and 80 mg/kg bw) showed changes in the stomach (thickening of the glandular mucosa) considered test substance related. There were no treatment related changes in body weight.


 


This acute oral study is classified as acceptable. It does satisfy with the guidelines requirements for an acute oral study (OECD 401) in the rats.


 


Under the test conditions, Chlorine dioxide at 0.2% is classified Category 3 (H301: Toxic if swallowed) according to the CLP regulation (1272/2008) and to the GHS, as the LD50 value is comprised between 50 and 300 mg/kg bw. Effects observed are related to the corrosive properties of ClO2.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
94 mg/kg bw
Quality of whole database:
The available information as a whole meets the tonnage driven data requirement of REACH. Moreover, reliability and consistency are observed across the study.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 December 2011 - 06 February 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP study conducted according to OECD Guideline 403 with restrictions: only 3 rats/sex are exposed at the highest concentrations by comparison with the other concentrations (5 rats/sex), 0.6 % aqueous chlorine dioxide (ClO2) solution, inherently stabilized without any explanation about the method used for stabilising the substance. Absence of any reported effects, due to the treatment, except the deaths of animals, according to dose levels. The physical state of the test atmosphere has not been characterized in the study. It is not clear whether or not the test atmosphere consists of gas of chlorine dioxide in liquid droplets. No justification for the selected concentration levels (achievable concentrations or anticipated effects from the acute toxicity by inhalation of gas)
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Remarks:
inspected on 25, 26, 27 & 28 November 2008 / signed on 12 November 2009
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: CD / Crl:CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Sulzfeld, Germany.
- Age at study initiation: Males: approx. 8 weeks; Females: approx. 9 weeks
- Weight at study initiation: Males: 231-290 g; Females: 218-250 g
- Fasting period before study: Feeding was discontinued approx. 16 h before test item administration
- Housing: During the 14-day observation period the animals were kept by sex in groups of 2-3 animals in MAKROLON cages (type III plus)
- Diet: Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: Drinking water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 55 ± 15 %
- Photoperiod: 12 h dark / 12 h light
Route of administration:
inhalation: mist
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Dynamic inhalation chamber (air changes/h (≥ 12 times))
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: Cylindrical exposure chamber (volume 40 L) which holds a maximum of 20 animals in pyrex tubes at the edge of the chamber in a radial position.
- Source and rate of air: Spray-jet was fed with compressed air (5.0 bar) from a compressor at a flow rate of 900 L/h and with the test item using an infusion pump at flow rates of 12, 20 and 50 mL/h. At the bottom of the exposure chamber, the air was sucked off at a lower rate than created by the spray-jet in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h).
- Air change: 22.5 changes per hour
- Method of conditioning air: A manometer and an air-flow meter were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and corrected, if necessary.
- The oxygen content in the inhalation chamber was 21 % v/v. It was determined at the beginning and at the end of the exposure with a DRÄGER Oxygen-analysis test set (DRÄGER Tube Oxygen 67 28 081). Carbon dioxide concentration did not exceed 1 %.
- Method of particle size determination: Analysis of the particle size distribution was carried out twice during the exposure period using a cascade impactor according to May, 1975.
- Treatment of exhaust air: Exhaust air was sucked through gas wash-bottles.
- Temperature, humidity, pressure in air chamber: The temperature (20.8-21.5 °C) and humidity (60.4-64.4 %) was checked and noted once every hour during the exposure period of the experiment.

TEST ATMOSPHERE
- Brief description of analytical method used: ClO2-concentrations in the inhalation chamber was determined by iodometric titration
- Aerosol samples were taken once every hour during the 4-hour exposure period. For that purpose, a probe was placed close to the animals’ noses and samples were collected by drawing 7.5 L air at a flow rate of 0.5 L/min for 15 minutes through 2 consecutive gas washing bottles containing approx. 50 mL 0.02 % potassium iodide solution (pH=2.0), each. The contents of both washing bottles were combined in an 1000 mL volumetric flask and filled up to the mark with water. An aliquot of 50 mL was used for the iodometric determination. Each sample was analysed twice.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The mist from the exposure chamber was drawn through the cascade impactor for 5 minutes at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance (SARTORIUS, type 1601 004, precision 0.1 mg).
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): In the inhalation chamber, close to the animals' noses, the spray-jet generated atmosphere had mass median aerodynamic diameters (MMAD) between 2.388 and 2.467 μm as determined with a cascade impactor. The Geometric Standard Deviations (GSD) of the MMAD were calculated as 2.69, 2.74 and 2.78.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.030, 0.047 and 0.074 mg/L air (iodometric determination).


The concentrations are acceptable based on the masse median aerodynamic diameter values of 2.388, 2.429 and 2.467 µm and the corresponding GSD values of 2.78, 2.74 and 2.69. This is inside the required range of 1-4 µm and 1.5-3, respectively as required by the OECD 403 guideline.
However,it is not reported if :
- these concentrations are the technical maximum achievable concentrations knowing that the measured concentrations as pure ClO2 are closed to the nominal concentrations which can be calculated taking into account both the air compressor flow rate (900L/h) and the ClO2 solution infusion pump flow rates (12, 20 et 50 mL/h).
- or if these concentrations are selected based on anticipated effects in rats as showed in the acute toxicity study by inhalation for the gas.
No. of animals per sex per dose:
3 animals/sex/dose at 0.074 mg/L air
5 animals/sex/dose at 0.030 and 0.047 mg/L air
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: A careful clinical examination was made at least once daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals.
Cageside observations included, but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well as somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Frequency of weighing: Individual body weights of animals were determined during the acclimatisation period on the day of exposure, prior to exposure and on test days 2, 4, 8 and 15 and at time of death if survival exceeded day 1. Changes in weight were calculated and recorded when survival exceeds one day. At the end of the test, the animals were weighed and sacrificed.
- Necropsy of survivors performed: Yes; Necropsy of all animals was carried out and all gross pathological changes were recorded.
Other examinations performed:
- The weight of the lungs was determined and recorded.
- No microscopic examination was carried out as no pathological findings were noted at necropsy.
Statistics:
No data
Preliminary study:
Not applicable
Sex:
male
Dose descriptor:
LC50
Effect level:
0.048 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
0.04 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.041 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
- Premature death was observed in 3/3 males and 3/3 females at the concentration of 0.074 mg/L air
- Premature death was observed in 2/5 males and 2/5 females at the concentration of 0.047 mg/L air.
- None of 5 male and 1/5 female animals died prematurely at the concentration of 0.030 mg/L air.
Clinical signs:
other:
Body weight:
All surviving animals gained the expected body weight.
Gross pathology:
No pathological findings were noted at necropsy.
Other findings:
None

Table 7.2.2/2: Summary of results

Symptoms/Criteria

Chlorine dioxide

0.074 mg/L air

0.047 mg/L air

0.030 mg/L air

Males (n=3)

Females (n=3)

Males (n=5)

Females (n=5)

Males (n=5)

Females (n=5)

Clinical signs:

Ataxia

+

0’-3 h

(3)

+

0’-3 h

(3)

+

0’-60’

(5)

+

0’-60’

(5)

+

0’-30’

(5)

+

0’-30’

(5)

Tremor

+

0’-60’

(3)

+

0’-60’

(3)

+

0’-60’

(5)

+

0’-60’

(5)

+

0’-30’

(5)

+

0’-30’

(5)

Dyspnoea

+-++

0’-3 h

(3)

+-++

0’-3 h

(3)

+

0’-3 h

(5)

+

0’-3 h

(5)

+

0’-2 d

(5)

+

0’-2 d

(5)

Mortality

Within 3 h

0

0

0

0

0

0

Within 24 h

3

3

2

2

0

1

Within 7 days

3

3

2

2

0

1

Within 14 days

3

3

2

2

0

1

Mean body weight (g)

Start

265.3

246.3

236.2

227.2

278.8

235.6

After 7 days

#

#

299.0

(+26.6)

250.3

(+10.2)

328.0

(+17.6)

249.8

(+6.0)

After 14 days

 

 

335.0

(+43.9)

268.0

(+19.3)

354.2

(+28.6)

259.0

(+11.2)

Inhibition of body weight gain

#

#

None

None

None

None

Necropsy findings

None

None

None

None

None

None

 

+ = slight; ++ = moderate; ' = minutes; h = hours; d = days; 0' = immediately after end of administration; # = all animals died prematurely

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Chlorine dioxide solutions have to be classified as Category 4 (H332: Harmful if inhaled) for acute inhalation toxicity (ATI4) above a concentration limit of 0.82%.
Executive summary:

In an acute inhalational toxicity study performed in accordance with GLP and OECD Guideline 403, groups of CD / Crl:CD(SD) rats were exposed to 0.6% aqueous chlorine dioxide (ClO2) solution, inherently stabilized *, at actual concentrations of 0.030, 0.047 and 0.074 mg/L air for 4 h by inhalation (mist) using a dynamic nose-only exposure chamber. The exposure concentrations were determined by iodometry.Animals were then observed for mortality, clinical signs and bodyweights for 14 days and necropsy was performed in all animals for macroscopical examination.


 


In the inhalation chamber, close to the animals' noses, the spray-jet generated atmosphere had mass median aerodynamic diameters (MMAD) between 2.388 and 2.467 μm as determined with a cascade impactor. The Geometric Standard Deviations (GSD) of the MMAD were calculated as 2.69, 2.74 and 2.78.


 


At the concentration of 0.074 mg/L air, slight ataxia, slight tremor and slight to moderate dyspnoea and premature death in all 3/3 male and 3/3 female animals. At the concentration of 0.047 mg/L air, slight ataxia, slight tremor and slight dyspnoea in all 5/5 male and 5/5 female animals. Two of 5 male and 2 of 5 female animals died prematurely. At the concentration of 0.030 mg/L air, slight ataxia, slight tremor and slight dyspnoea in all 5/5 male and 5/5 female animals. None of 5 male and 1/5 female animals died prematurely. All surviving animals gained the expected body weight. No pathological findings were noted at necropsy.


 


LC50 for males and females were 0.048 and 0.040 mg/L air/4 h, respectively. LC50 males and females combined (14 days): 0.041 mg/L air/4 h as pure ClO2. Therefore, based on the calculation method of CLP, the LC50value corresponds to 6.83 mg 0.6% ClO2 solution/L air/4h as pure ClO2 which is lower to the classification limit for a mist (5 mg/L) according to the CLP.


 


According to the study results, and applying the classification criteria for acute inhalation toxicity (5 mg/L for mist/aerosol), chlorine dioxide solutions have to be classified as category 4 for acute inhalation toxicity (ATI4) above a concentration limit of 0.82%, based on prorata of concentration according to CLP Regulation (EC) 1272/2008 (6.83 mg/L x 0.6% / 5 mg/L).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
6 830 mg/m³ air
Physical form:
inhalation: dust / mist
Quality of whole database:
The available information as a whole meets the tonnage driven data requirement of REACH. Moreover, reliability and consistency are observed across the study.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral

A study was identified as the key study (Tos, 1996).The study was conducted according to the OECD guideline No. 401 and in compliance with GLP. Rats were administered Chlorine dioxide (as a 0.2 % solution in water) by gavage at doses of 20, 40 and 80 mg/kg bw.

Animals treated at the lowest dose showed hypoactivity, piloerection and hunched posture during the first three days of the study. Females treated at 40 mg/kg bw showed the same clinical signs up to day 5 of the study. Males treated at 40 mg/kg bw and all animals treated at the highest dose showed clinical signs involving the CNS, the respiratory tract, and also piloerection, hunched posture and salivation. All reviving animals recovered within days 4 -7 of the study. The autopsy of animals which died during the study showed test substance-related changes in the gastrointestinal tract: congestion and erosions with mucus or test substance presence in the stomach and thinning walls with catarrhal or catarrhal-haemorrhagic content in the intestine. Congestion of the lungs, of the kidneys and of the liver and decreased size of the spleen were also observed. Animals treated at 20 mg/kg bw not show any necroscopic changes at the autopsy performed at the end of the study. The surviving animals treated at the highest doses (40 and 80 mg/kg bw) showed changes in the stomach (thickening of the glandular mucosa) which were considered test substance related.

Oral LD50Combined = 93.86 mg/kg bw (95% C.L. of 45.52 -193.53 mg/kg bw). Observed effects are related to the corrosive properties of ClO2.

 

Acute toxicity: dermal

In accordance with REACH requirements, the acute dermal toxicity study (required in section 8.5.3) does not need to be conducted as results for two routes of exposure (oral and inhalation) are already available.

 

Acute toxicity: inhalation

Chlorine dioxide (Gas)

A study was identified as the key study (Schorsch et al., 1996). The study was conducted according to the EU Method B.2 and in compliance with GLP. Rats were exposed by oro-nasal inhalation to Chlorine Dioxide gas for 4 hours at analytical concentrations of 0, 46, 71, 107 and 128 mg/m3. Clinical signs observed in all dose groups included: respiratory distress (abdominal respiration, noisy respiration, laboured respiration and nasal secretion) and general weakness (piloerection, hunched back, decrease of activity and weight loss / thin body condition). Lungs from treated animals showed frequent mottling, redness and depressed area. The main lesion induced by ClO2 is the destruction of alveolar walls, which created dose-related pulmonary emphysema lesions. Inhalation LC50combined = 89 mg/m3 air (95% CL 69 -119 mg/m3).

Chlorine dioxide (Solution)

In a key study performed in accordance with GLP and OECD Guideline 403, groups of CD / Crl:CD(SD) rats were exposed to 0.6% aqueous chlorine dioxide (ClO2) solution, inherently stabilized *, at actual concentrations of 0.030, 0.047 and 0.074 mg/L air for 4 h by inhalation (mist) using a dynamic nose-only exposure chamber. The exposure concentrations were determined by iodometry.Animals were then observed for mortality, clinical signs and bodyweights for 14 days and necropsy was performed in all animals for macroscopical examination.

 

In the inhalation chamber, close to the animals' noses, the spray-jet generated atmosphere had mass median aerodynamic diameters (MMAD) between 2.388 and 2.467 μm as determined with a cascade impactor. The Geometric Standard Deviations (GSD) of the MMAD were calculated as 2.69, 2.74 and 2.78.

 

At the concentration of 0.074 mg/L air, slight ataxia, slight tremor and slight to moderate dyspnoea and premature death in all 3/3 male and 3/3 female animals. At the concentration of 0.047 mg/L air, slight ataxia, slight tremor and slight dyspnoea in all 5/5 male and 5/5 female animals. Two of 5 male and 2 of 5 female animals died prematurely. At the concentration of 0.030 mg/L air, slight ataxia, slight tremor and slight dyspnoea in all 5/5 male and 5/5 female animals. None of 5 male and 1/5 female animals died prematurely. All surviving animals gained the expected body weight. No pathological findings were noted at necropsy.

 

LC50 for males and females were 0.048 and 0.040 mg/L air/4 h, respectively.

LC50 males and females combined (14 days): 0.041 mg/L air/4 h as pure ClO2. Therefore, the LC50 value corresponds to 6.83 mg 0.6% ClO2 solution/L air/4h which is lower to the classification limit for a mist according to the CLP.

 

According to the study results, and applying the criteria for classification for acute inhalation toxicity (mist/aerosol), chlorine dioxide solutions have to be classified as category 4 for acute inhalation toxicity (ATI4) with a specific concentration limit (i.e. threshold concentration, below which no classification of the solution is warranted) of 0.82%, based on prorata of concentration according to CLP Regulation.

Justification for classification or non-classification

Aqueous solutions:

Chlorine dioxide 0.2% is classified for acute oral toxicity as:

- Category 3 (H301 Toxic if swallowed) according to the CLP Regulation (1272/2008) as LD50was found to be between 50 and 300 mg/kg b.w.

This is consistent with the minimum CLH, and no more severe classification is proposed for solutions with higher concentrations, as effects will be due to corrosivity and not to intrinsic toxicity.

Solutions ranging between 0.5 and 2% as registered will also fall into ATO category 3.

 

Chlorine dioxide 0.6% is not classified for acute inhalation toxicity:

Based on the results of Haferkorn study (2012), the LC50 is above the classification threshold of 5 mg/L. However, considering the prorata of concentration, solutions above 0.82% must be additionally self-classified as ATI cat.4

 

In addition, the current CLH for Chlorine dioxide in solution lead to the classification as STOT-SE category 3 at the concentration limit greater than 3%.

 

Gas:

Based on the results of the key study (Schorsch et al., 1996), Chlorine dioxide is classified for acute inhalation toxicity as:

- Category 1 (H330 Fatal if inhaled) according to the CLP Regulation (1272/2008) as LD50was found to be between 0 and 100 ppm (gas).

This is more severe than the minimum CLH.

 

Based on the mechanism of action (corrosivity), additional labelling EUH071 for the gas is needed: corrosive to the respiratory tract.

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