Administrative data

Purpose flag:
supporting study
Study result type:
read-across based on grouping of substances (category approach)
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
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.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1984

Materials and methods

Test guideline
Qualifier:
no guideline followed
Methods:
in vivo
Principles of method if other than guideline:
ADME study on Alcide® gel by dermal route.
GLP compliance:
no data
Objective of studyopen allclose all

Test materials

Identity of test material same as for substance defined in section 1 (if not read-across):
no
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 and environmental conditions:
Weight at study initiation: 270-290 g 

Administration / exposure

Route of administration:
other: dermal and oral (gavage)
Vehicle:
unchanged (no vehicle)
Details on exposure:
To reach a plateau concentration of the drug, Alcide gel was applied to the shaven backs of rats for a period of 10 days. On the 11th day, 36C-labeled Alcide gel, which contained NaClO2 in Part A, was administered to the animals, which had been fasted for 24 hrs. To prevent oral ingestion of the radioactive compound, animals backs were covered with a plastic wrap securely taped to the rat.
Duration and frequency of treatment / exposure:
Dermal: daily for 10 days
Oral: once on day 11
Doses / concentrations:
Dermal: 2000 mg/kg bw/d
Oral: 2000 mg/kg 
No. of animals per sex per dose:
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

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

Metabolite characterisation studies

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

Bioaccessibility

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.