Chlorine dioxide

Acute Toxicity: oral

Administrative data

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

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

Chlorine dioxide

EC Number:

233-162-8

EC Name:

Chlorine dioxide

Cas Number:

10049-04-4

Molecular formula:

ClO2

IUPAC Name:

Chlorine Dioxide

Details on test material:

Specification: 0.2% solution (stated in report as 2 ‰ solution)
Description: Yellow aqueous solution

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:

No data

Effect levels

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

Any other information on results incl. tables

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)

Applicant's summary and conclusion

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.