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Toxicological information

Acute Toxicity: oral

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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-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
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 guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
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 generated from sodium chlorate and hydrogen peroxide in the presence of a strong acid
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:
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 study and in addition, sporadic cases of reddish nasal discharge, shallow breathing and salivation during the first two hours after the test article administration. Males treated at 40 mg/kg and all animals treated at the highest dose (80 mg/kg) showed clinical signs involving the CNS (hypoactivity or sedation), the respiratory tract (respiratory rattles, shallow breathing, gasping, reddish nasal discharge) and also piloerection, hunched posture and salivation. These signs started from 30 minutes to 24 hours and lasted up to 30 minutes to day 6 of the study. Diarrhoea and pallor of the skin and apparent mucosae were also observed in animals treated at 80 mg/kg during the first two days of the study. All reviving animals recovered within days 4 – 7 of the study.
Body weight:
Body weight gain of animals treated at the lowest dose was considered within normal limits for animals of this species and age. Decrease in body weight was noted only at day 3 weighing in almost all animals treated at the other doses.
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:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
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). Chlorine dioxide at 0.2% is classified as toxic if swallowed (T;R25) according to the Directive 67/548/EEC and in category 3 according to the CLP regulation (1272/2008).
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 as toxic if swallowed (T; R25) according to the Directive 67/548/EC and in category 3 according to the CLP regulation (1272/2008). Effects observed are related to the corrosive properties of ClO2.