Acute Toxicity: oral.001 to 002

Acute Toxicity: oral.001

Administrative data

Study result type:

experimental result

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

Only short abstract available

Data source

Reference

Reference Type:

publication

Title:

Experimental observation on acute toxicity and irritative effect of stable chlorine dioxide.

Author:

Laishun S and Chaoren X

Year:

1999

Bibliographic source:

Chinese Journal of Disinfection, 16(1): 40

Materials and methods

Principles of method if other than guideline:

Not specified

GLP compliance:

no data

Test materials

Identity of test material same as for substance defined in section 1 (if not read-across):

yes

Test material identityopen allclose all

Test material identity 1

Test material identity 2

Test material identity 3

Details on test material:

No data

Test animals

Species:

mouse

Strain:

no data

Sex:

no data

Details on test animals and environmental conditions:

Numbers: not specified.

Administration / exposure

Details on oral exposure:

No data

Doses:

No data

No. of animals per sex per dose:

No data

Control animals:

no data

Details on study design:

No data

Statistics:

No data

Results and discussion

Effect levels

Sex:

no data

Endpoint:

LD50

Effect level:

> 10 000 mg/kg bw

Mortality:

No data

Clinical signs:

No data

Body weight:

No data

Gross pathology:

No data

Other findings:

No data

Any other information on results incl. tables:

No data

Applicant's summary and conclusion

Conclusions:

Under the test conditions, Chlorine dioxide solution is non toxic.

Executive summary:

Under the test conditions, Chlorine dioxide is non toxic according to the results of this test.

Criteria used for interpretation of results:

EU

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 REAC

Acute Toxicity: oral.002

Administrative data

Purpose flag:

key study

Study result type:

experimental result

Study period:

1995-03-15 to 1995-04-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report Date:

1996

Materials and methods

Test guidelineopen allclose all

Test guideline 1

Test guideline 2

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test materials

Identity of test material same as for substance defined in section 1 (if not read-across):

yes

Test material identityopen allclose all

Test material identity 1

Test material identity 2

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 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 (if fixed dose study):

No data

Effect levels

Sex:

male/female

Endpoint:

LD50

Effect level:

93.86 mg/kg bw

Based on:

test mat.

95% CL:

45.52 - 193.53

Remarks:

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

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.

Interpretation of results:

Toxicity Category III

Criteria used for interpretation of results:

EU