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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Alcide is a germicidal preparation which has been shown to kill a wide range of common pathogenic bacteria as well as fungi, in vitro. This preparation is composed of part A and part B which contains sodium chlorite and lactic acid as the active in gradients, respectively. The two parts are combined in equal volumes immediately prior to application resulting in the formation of chlorine dioxide. Therefore, we can consider that the animal are exposed to chlorine dioxide and also to chlorite. The study is well conducted but no data on the GLP and no guideline followed.
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:
publication
Title:
Unnamed
Year:
1984

Materials and methods

Objective of study:
absorption
distribution
excretion
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
ADME study on Alcide® gel by dermal route.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
Alcide Gel
IUPAC Name:
Alcide Gel
Details on test material:
Alcide is a germicidal preparation which has been shown to kill a wide range of common pathogenic bacteria as well as fungi, in vitro. This preparation is composed of part A and part B which contains sodium chlorite and lactic acid as the active in gradients, respectively. The two parts are combined in equal volumes immediately prior to application resulting in the formation of chlorine dioxide.
Radiolabelling:
yes
Remarks:
36Cl

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
Weight at study initiation: 270-290 g

Administration / exposure

Route of administration:
other: dermal and oral (gavage)
Vehicle:
unchanged (no vehicle)
Duration and frequency of treatment / exposure:
Dermal: daily for 10 days
Oral: once on day 11
Doses / concentrations
Remarks:
Doses / Concentrations:
Dermal: 2000 mg/kg bw/d
Oral: 2000 mg/kg
No. of animals per sex per dose / concentration:
Absorption, distribution and elimination study:
10 females (group 1: for haematological analysis), 4 females (group 2, for histological observations) and one control

Excretion and metabolism study:
4 females
Control animals:
yes, concurrent no treatment
Details on dosing and sampling:
Sampling time:
Absorption, distribution and elimination study:
0.5, 1,2,4,6,8,24,48,72,96,120,144 and 168 hours (blood)
Excretion and metabolism study:
8, 16, 24, 48, 72, 96, 120, 144 and 168 hours (urine)
24, 48, 72 and 96 hours (faeces and expired air)

Samples:
Absorption, distribution and elimination study:
group 1: blood
group 2: tissue samples of liver, kidney, lung, stomach, duodenum, ileum, spleen, bone marrow, fat, brain and ovary
Excretion and metabolism study:
urine, faeces and expired air

Results and discussion

Preliminary studies:
not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Maximum absorption of 36Cl into plasma was observed after 72 hrs where a concentration of 69.4 µg% of 36Cl was reached. The half-life for 36Cl absorption was 22.1 hours, corresponding to a rate constant of 0.0314 hr-1. The t1/2 for 36Cl elimination from plasma was 64.0 hours, corresponding to a rate constant of 0.0108 hr-1.
Details on distribution in tissues:
The greatest amount of radioactivity was found in whole blood followed by kidney, plasma, skin (untreated area), ovary, lung, ileum, spleen, brain, duodenum, liver, stomach, bone marrow, carcass and fat (see table 7.1.1/2).
Details on excretion:
Following dermal application of Alcide gel, urinary excretion of radioactivity was greatest in the first 24 hours (see table 7.1.1/3). Radioactivity was excreted in the form of chloride and chlorite, while chlorate was not detected. Radioactivity was not detected in faeces and expired air at any time point studied. The total excretion of chlorite was approximately 18.3 µg 36Cl.

The half life for elimination of 36Cl compounds from plasma was longer than that of chlorine dioxide administered orally. The reason for this is that it is possible that contact of Alcide gel with skin resulted in a reduction of chlorine dioxide to chlorite and chloride.
Toxicokinetic parametersopen allclose all
Toxicokinetic parameters:
half-life 1st: absorption 22.1 hours
Toxicokinetic parameters:
half-life 2nd: elimination 64.0 hours

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The metabolites of chlorine dioxide were identified as chlorite and chloride.

Any other information on results incl. tables

Table 7.1.1/2: Distribution of36C-labeled compounds in rat 96 hrs after alcide administration

36Cl content

(ng/ml or g)

36Cl content

(ng/ml or g)

Whole blood

571.1 ± 199.4

Brain

324.3 ± 96.7

Kidney

545.4 ± 80.8

Duodenum

304.9 ± 70.7

Plasma

525.1 ± 180.7

Liver

195.5 ± 52.8

Skin untreated

512.6 ± 93.8

Stomach

185.4 ± 48.5

Ovary

428.7 ± 96.8

Bone marrow

61.8 ± 45.3

Lung

421.3 ± 87.8

Carcass

29.4 ± 29.4

Lleum

342.4 ± 81.2

Fat

28.0 ± 28.0

Spleen

326.8 ± 55.7

Table 7.1.1/3: Excretion of36Cl-labelled compounds in rat

 

Collection period (hr)

36Cl in Urine (total µg)

0 – 8

0.80 ± 0.45a

8 – 16

3.94 ± 1.32

16 – 24

9.00 ± 3.03

0 – 24

13.74

24 – 48

12.42 ± 2.23

48 – 72

7.85 ± 0.60

72 – 96

7.12 ± 0.86

86 – 120

7.30 ± 2.14

120 - 144

7.96 ± 1.73

144 – 168

3.74 ± 0.22

0 -168

60.13

avalues represent the mean ± SE from four rats expressed as total µg36Cl excreted

Table 7.1.1/4: Metabolites of [36Cl] Alcide in rat urine

 

Collection period (hr)

Cl-

ClO2-

16 – 24

3.90 ± 0.93a

4.99 ± 2.18

24 – 48

6.05 ± 1.55

5.61 ± 1.04

48 – 72

3.39 ± 0.12

4.29 ± 0.79

72 – 96

3.39 ± 0.73

3.36 ± 1.30

avalues represent the mean ± SE from four rats expressed in µg36Cl

Applicant's summary and conclusion

Conclusions:
Topical application of Alcide gel resulted in a slow rate of absorption of 36Cl labelled compounds with a half life of 22.1 h. Both ClO2 and ClO2- are water soluble and slightly lipophilic, which could account for the decreased rate of absorption compared to the rat of absorption after an oral administration.
The half life for elimination from plasma was 64 h. This half-life was longer than that of ClO2 alone (43.9 hr) administered orally. It is possible that contact of alcide gel with skin resulted in a reduction of ClO2 and ClO2- to Cl-.
The excretion of 36Cl labelled compounds was by the kidney, with Chloride and chlorite as the metabolites.
Executive summary:

Female Sprague-Dawley rats were exposed dermally to Alcide gel, which is composed of two part (sodium chlorite and lactic acid). When the two parts are mixing, Chlorine dioxide (ClO2) is formed immediately. So we can consider that the animals are immediately exposed to the chlorine dioxide when the gel is applied on the back of the animal. Animals were exposed for 10 days at the dose of 2000 mg/kg of chlorine dioxide. On the 11th day the animals which had been fasted for 24 hrs received 36Cl-labelled Alcide gel. To prevent oral ingestion of the radioactive compound, animals backs were covered with a plastic wrap securely taped to the rat. Following several times after the application of the gel, blood samples, tissues, urine, faeces and expired air were collected for analysis and quantification of 36Cl compounds.

Topical application of Alcide gel resulted in a slow rate of absorption of 36Cl labelled compounds with a half life of 22.1 h. Both ClO2 and ClO2- are water soluble and slightly lipophilic, which could account for the decreased rate of absorption compared to the rate of absorption after an oral administration. The half life for elimination from plasma was 64 h. This half-life was longer than that of ClO2 alone (43.9 hr) administered orally. It is possible that contact of alcide gel with skin resulted in a reduction of ClO2 and ClO2- to Cl-. The excretion of 36Cl labelled compounds was by the kidney, with Chloride and chlorite as the metabolites.