Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: No data on the concentration of the substance sodium chlorite in the antimicrobial compound tested.

Data source

Reference
Reference Type:
publication
Title:
Pharmacodynamics of Alcide, a new antimicrobial compound, in rat and rabbit
Author:
Scatina JA, Abdel-Rahman MS, Gerges SE, Khan MY and Gona O
Year:
1984
Bibliographic source:
Fundamental and Applied Toxicology, 4: 479-484

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The dermal toxicity of Alcide gel was assessed following application of the gel to the backs of rabbits 5 days/week for 3 months.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Alcide Gel is a preparation composed of sodium chlorite and lactic acid, which when combined in equal volumes results in the formation of chlorine dioxide.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Forty rabbits (1.57 - 1.64 kg), twenty of each sex were used in the studies.

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Duration of treatment: 3 months
Frequency of treatment:
Alcide gel was applied 5 days/week
Doses / concentrationsopen allclose all
Dose / conc.:
0.5 other: g/kg
Remarks:
Doses were administered on a gel weight basis containing 50 % Part A and 50 % Part B.
Dose / conc.:
1 other: g/kg
Remarks:
Doses were administered on a gel weight basis containing 50 % Part A and 50 % Part B
Dose / conc.:
2 other: g/kg
Remarks:
Doses were administered on a gel weight basis containing 50 % Part A and 50 % Part B
No. of animals per sex per dose:
4 rabbits/sex/group
Control animals:
other: Eight animals received 2.0 g/kg of a placebo gel which contains the gelling material alone without the active ingredients. Another group served as the control and did not receive any treatment.
Details on study design:
Any test material remaining on the skin following the daily exposure was washed off prior to the new application.

Examinations

Sacrifice and pathology:
After 3 months, blood was collected from all animals by cardiac puncture. White blood cell count, red blood cell count, haemoglobin concentration, packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin and mean corpuscualr haemoglobin concentration were determined.Clinical studies were conducted after 90 days. The remainder of the blood was used for the determination of glutathione (GSH), osmotic fragility and methemoglobin.Organ/ body weight ratios were calculated .The liver, kidney, lung, heart, ovary/testes, spleen, skin, stomach, duodenum and ileum from all rabbits were examined microscopically while microscopic examination of brain, pancreas, adrenals and thyroid was done only on aniamls from the high dose and control groups.
Statistics:
Statistical analysis of food consumption, body weight, haematology, clinical chemistry, glutathione, osmotic fragility and organ/ body weight ratios were performed using an analysis of variance test and Duncan's multiple range test.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNSAll rabbits appeared healthy throughout the 90 day treatment period. DERMAL IRRITATIONNo changes were found at physical examination of the application sites during the experiment.FEED CONSUMPTION AND BODY WEIGHTThese parameters were not significantly altered at any time point.CLINICAL CHEMISTRY AND HAEMATOLOGYIn the 2.0 g/kg Alcide grooup as well as in the placebo group, creatinine values were elevated in serum, 1.60 ± 0.06 and 1.64 ± 0.07 vs 1.32 ± 0.08 for the control group, respectively. In addition the blood urea nitrogen/ creatinine ratio was reduced in the 2.0 g/kg group, 11.5 ± 0.8 compared to 14.6 ± 1.1 for the control group. In the 1.0 g/kg Alcide group, the carbon dioxide content was increased in serum while the serum inorganic phosphorous and calcium concentrations were decreased in serum.No significant changes were noted in experimental aniamls compared to controls for any of the haematological parameters studied.Glutathione content in blood was significantly decreased in the group receiving 2.0 g/kg Alcide gel as well as in the placebo gel group which also received 2.0 g/kg. Erythrocyte osmotic fragility was not altered and methemoglobin was not detected in blood.ORGAN WEIGHTIn the group receiving 1.0 g/kg of Alcide gel, the liver/ body weight ration was significantly increased compared to the control group.PATHOLOGYAll organs appeared normal.HISTOPATHOLOGYNo histological changeswere observed in the livers of either this group or in any other treatment group. Adrenal cortical hyperplasia was observed in all animals examined , including the control group and was the only significant histopathological alteration observed.

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
2 other: g/kg

Target system / organ toxicity

Key result
Critical effects observed:
no

Any other information on results incl. tables

 Treatment  GSH (mg %) Haemolysis (%
 Control  33.6 ± 1.5 a 64.8 ± 1.3 
 0.5 g/kg 31.6 ± 1.6  69.4 ± 3.5 
 1.0 g/kg 29.4 ± 3.3   62.9 ± 2.9
2.0 g/kg  24.0 ± 1.4  71.7 ± 3.8 
Placebo (2.0 g/kg) 24.6 ± 1.8 b 66.4 ± 4.6 

a Values represent the mean ± SE of glutathione and percentage haemolysis from 7 - 8 animals/ group

b Significantly different from control

Applicant's summary and conclusion

Conclusions:
In the dermal toxicity study using rabbits, no gross signs of toxicity were observed. Feed consumption and body weights remained stable during the treatment period. Glutathione concentrations in blood were decreased in the group receiving 2.0 g/kg Alcide gel as well as in the placebo gel group which received the same concentration. The 1.0 and 0.5 g/kg Alcide groups did not have any alterations in glutathione content. This observation suggests that the gel itself was responsible for glutathione depletion. However, 2.0 g/kg represents a dose which was 100 fold higher than that proposed for use in humans. Adrenal cortical hyperplasia which was noted in treated as well as in control animals was most likely related to animal stress.
Executive summary:

The dermal toxicity of Alcide gel was assessed following application of the gel to the backs of rabbits 5 days/week for 3 months. n the dermal toxicity study using rabbits, no gross signs of toxicity weere observed. Feed consumption and body weights remained stable during the treatment period. Glutathione concentrations in blood were decreased in the group receiving 2.0 g/kg Alcide gel as well as in the placebo gel group which received the same concentration. The 1.0 and 0.5 g/kg Alcide groups did not have any alterations in glutathione content. This observation suggests that the gel itself was responsible for glutathione depletion. However, 2.0 g/kg represents a dose which was 100 fold higher than that proposed for use in humans. Adrenal cortical hyperplasia which was noted in treated as well as in control animals was most likely related to animal stress.