Repeated dose toxicity: dermal.001
Administrative data
- Study result type:
- experimental result
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- Alcide gel was used in this study (antimicrobial compound consisting of solutions of sodium chlorite and lactic acid that produce chlorine dioxide when mixed)
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:
- no data
- Test type:
- subchronic
- Limit test:
- no
Test materials
- Identity of test material same as for substance defined in section 1 (if not read-across):
- no
- 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:
- no data
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- No data
- Analytical verification of doses or concentrations:
- no data
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- Duration of treatment: 3 months
- Frequency of treatment:
- Alcide gel was applied 5 day/week
Doses / concentrations
- Doses / concentrations:
- 0.5, 1.0 and 2.0 g/kg
- Basis:
- other: 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.
- Positive control:
- No data
Examinations
- Observations and examinations performed and frequency:
- No data
- 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 animals from the high dose and control groups. - Other examinations:
- No data
- 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 and mortality:
- no effects
- Dermal irritation:
- no effects
- Body weight and weight gain:
- no effects
- Food consumption:
- no effects
- Food efficiency:
- not examined
- Water consumption:
- not examined
- Ophthalmoscopic examination:
- not examined
- Haematology:
- yes
- Clinical chemistry:
- yes
- Urinalysis:
- not examined
- Neurobehaviour:
- not examined
- Organ weights:
- yes
- Gross pathology:
- yes
- Histopathology: non-neoplastic:
- yes
- Histopathology: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS
All rabbits appeared healthy throughout the 90 day treatment period.
DERMAL IRRITATION
No changes were found at physical examination of the application sites during the experiment.
FEED CONSUMPTION AND BODY WEIGHT
These parameters were not significantly altered at any time point.
CLINICAL CHEMISTRY AND HAEMATOLOGY
In the 2.0 g/kg Alcide group 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 WEIGHT
In the group receiving 1.0 g/kg of Alcide gel, the liver/ body weight ration was significantly increased compared to the control group.
PATHOLOGY
All organs appeared normal.
HISTOPATHOLOGY
No histological changes were 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. - Any other information on results incl. tables:
- No data
Applicant's summary and conclusion
- Executive summary:
- In a subchronic toxicity study, Chlorine Dioxide (ClO2) under Alcide gel form, was applicated on the backs of forty male and female New Zealand White rabbits at dose levels of 0.5, 1.0 and 2.0 g/kg bw for three months.An animal group received 2.0 g/kg bw of a placebo gel which contains the gelling material alone without the active ingredients whereas another animal control group did not received any treatment.After three months, blood was collected from all animals, clinical studies were conducted, organ/body weight ratios were calculated and several tissues were examined microscopically.All rabbits appeared healthy at the end of the experiment and no changes were found at physical examination of the application sites during the experiment. 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.No significant changes were noted in experimental animals compared to controls for any of the haematological parameters studied.In the group receiving 1.0 g/kg of Alcide gel, the liver/ body weight ration was significantly increased compared to the control group.No histological changes were observed in the livers of either this group or in any other treatment group.In this dermal toxicity study using rabbits, no gross signs of toxicity were observed.
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