Registration Dossier

Administrative data

Endpoint:
dermal absorption
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure described in sufficient detail but the study design set up prior to OECD test guidelines and GLP.

Data source

Reference
Reference Type:
publication
Title:
Zur Problematik der Tierverträglichkeit von Peressigsäure, 2. Mitt., Qualitäts und Rückstandsuntersuchungen an Fleisch nach Applikation von peressigsäurehaltigen Lösungen auf die Haut von Schweinen
Author:
Krüger S. and Jancke S.
Year:
1976
Bibliographic source:
Monatshefte Vet Med 31: 65-68

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the investigation was performed.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
no

Test animals

Species:
pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
Pigs (initial weight approx. 33 kg)

Administration / exposure

Type of coverage:
other: in vitro: Pig skin was mounted between two discs with a diameter of 4.5 cm each (yielding an exposed skin area of about 15.7 cm2).
Vehicle:
physiological saline
Duration of exposure:
In vivo: Subchronic trial: 120 days
In vitro: Dermal penetration study: 24 hours
Doses:
1.5 % Wofasteril solution for the subchronic trials
0.8 % for the in vitro diffusion trial through untreated and pretreated pig skin

No. of animals per group:
19 pigs.
Details on study design:
In view of the use of peracetic acid containing products for the disinfection of stables, the cutaneous tolerability and penetration of peracetic acid following topical application of diluted peracetic acid alone and a diluted Wofasteril solution (application concentration in both cases 1.5 % peracetic acid) was investigated in a subchronic 120-day study in a total of 19 pigs. Pigs (initial weight approx. 33 kg) were treated with a dose of 250 mL/animal/day corresponding to a daily dose of about 114 mg/kg bw/day. Groups of 5 pigs each were kept in separate stable boxes. After termination of the study, the meat quality was studied by analysing residues in muscles, liver and adipose tissue. In an accompanying model trial the penetration of peracetic acid through treated and untreated skin was investigated.

The meat quality was assessed by measuring pH, colour brightness of the meat and the water binding capacity. The pH value was measured 1 and 24 hours post mortem. For the determination of pH and brightness, meat samples were taken from the M. longissimus dorsi. Residues of peracetic acid and its metabolite hydrogen peroxide in muscles, liver and adipose tissue were determined by a method measuring the conversion of Fe2+ from FeCl2 to Fe3+ (Kostenko method, 1968) and the oxidation of iodide to iodine using starch as the indicator (Turner method, 1930).
For the diffusion of peracetic acid through pig skin in vitro, skin samples with a size of up to 15.7 cm2 were subjected to diffusion trials. From each pig of the control and treatment groups, 2 pieces of skin (skin site not stated) were used. In a special diffusion device manufactured for this trial, the penetration of peracetic acid from a total quantity of 110 mL of a peracetic acid or Wofasteril solution both containing 0.8 % of peracetic acid through the epidermis was studied over a period of 24 hours at a temperature of 37 °C. Physiological saline was used as the receptor fluid. The skin was mounted such in the device that the subcutis was faced the receptor fluid.
Details on in vitro test system (if applicable):
A special diffusion device was used for this study. Pig skin was mounted between two discs with a diameter of 4.5 cm each (yielding an exposed skin area of about 15.7 cm2). A container with two open sides was glued with one of the open side onto the disc. A volume of 110 mL of a 0.8 % peracetic acid solution or a total quantity of 880 mg of peracetic acid (prepared by a dilution of “pure” peracetic acid or Wofasteril) was filled into the donor part of the container, while the receptor part contained a volume of 110 mL of physiological saline as the receptor fluid. Skin was mounted such between the two discs that the epidermis faced the donor chamber while the subcutis faced the receptor chamber.

Results and discussion

Signs and symptoms of toxicity:
no effects
Dermal irritation:
not specified
Percutaneous absorption
Parameter:
percentage
Absorption:
ca. 0.3 %
Remarks on result:
other: 24 hours

Any other information on results incl. tables

Preliminary studies

Method of analysis:

The determination of peracetic acid in the receptor fluid was conducted according to a modified method of Turner measuring peracetic acid by the oxidation of potassium iodide to iodine in the presence of starch as the quantitative indicator for this reaction. The limit of quantification of the method used was shown to be as low as 2 µg peracetic acid (absolute). 

 

Pharmacokinetic studies

Absorption:

After a period of 24 hours, no detectable amounts of peracetic acid were found in the receptor fluid. In one of eight skin samples which was obtained from a pig revealing skin damage of the deeper skin layers, a total quantity of 2.6 mg of peracetic acid was found in the receptor fluid which corresponds to a skin absorption of about 0.3 % (2.6 mg/880 mg = 0.3 %).

 

Additional information:

No radioactive material was used. The results demonstrated that there were no detectable amounts of peracetic acid in the receptor fluid when intact skin was used.

In one of eight diffusion trials performed, penetration of peracetic acid could be detected and a total quantity of 2.6 mg was found. Penetration was restricted to one pig skin sample which revealed skin damage affecting also deeper skin layers.

Applicant's summary and conclusion

Conclusions:
The subchronic study with pigs demonstrated that following cutaneous application of peracetic acid or Wofasteril onto the skin of pigs for the disinfection of occupied pig stables, no adverse effects on meat quality and no detectable residues of peracetic acid and/or its metabolite hydrogen peroxide were observed in muscles, liver and adipose tissue, respectively.
Furthermore, results of the skin penetration trials performed with a specially devised diffusion cell demonstrated no penetration of peracetic acid through intact and treated skin. Penetration through skin could only be observed in one pig which revealed skin damage affecting also deeper skin layers.
Executive summary:

In view of the use of peracetic acid containing products for the disinfection of stables, the cutaneous tolerability and penetration of peracetic acid following topical application of diluted peracetic acid alone and a diluted Wofasteril solution (application concentration in both cases 1.5 % peracetic acid) was investigated in a subchronic 120-day study in a total of 19 pigs. Pigs (initial weight approx.) were treated with a dose of 250 mL/animal/day corresponding to a daily dose of about 114 mg/kg bw/day. Groups of 5 pigs each were kept in separate stable boxes.

 

Slaughter samples taken demonstrated no histological nor organoleptic changes in the test and control groups. There was no influence on pH and colour brightness of the meat following topical treatment with peracetic acid and Wofasteril demonstrating no effect of peracetic acid on meat quality.

 

Analysis of muscles, liver and adipose tissue on residues of peracetic acid and its metabolite hydrogen peroxide were negative by the methods used. The results lead to the conclusion that peracetic acid and hydrogen peroxide either did not penetrate pig skin in vivo or degraded rapidly resulting in non-detects in these organs/tissues.

 

The results of the diffusion trials of peracetic acid through treated and untreated pig skin in vitro demonstrated that no penetration of peracetic acid through pig skin was found through intact skin while absorption of peracetic acid through damaged skin cannot be entirely excluded.