Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: See below, a 5-day RF study was started but had to be finished prematurely because of rapid and severe skin reactions.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Deviations:
yes
Remarks:
see below
Principles of method if other than guideline:
The 28-day test was cancelled because of rapid and severe skin reactions during the 5-day dose range-finding test. See below.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
not specified
Details on exposure:
The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Duration of treatment / exposure:
6 hours per day for 5 days
Frequency of treatment:
Once daily for 5 days. Application was performed approximately the same time each day.
No. of animals per sex per dose:
3 per sex/dose for 300 and 1000 mg/kg bw groups
3 males for 30 and 100 mg/kg bw groups
Details on study design:
Dose levels of 30 and 100 mg/kg/day were based on the results of a previous pilot study using dose levels of 300 and 1000 mg/kg/day (NOTOX project 326734). In that study severe irritation/corrosion was observed among all animals.
Since a dose volume higher than 7.5 ml/kg is practically impossible taking into account the size of the patch and the maximum body weights to be expected in the main study, dose levels lower than 300 mg/kg/day were selected in order
to minimize/prevent ethically unacceptable irritation.

Results and discussion

Results of examinations

Dermal irritation:
effects observed, treatment-related
Details on results:
In a 5 day dermal range-finding study corrosive effects were observed at the 1000 and 300 mg/kg dose level. Therefore, a new pilot study was conducted using dose levels of 30 and 100 mg/kg body weight/day at the maximized dose volume of 7.5 ml/kg body weight. Again severe local effects were noted. As in the first pilot study no skin effects were seen on the first 2-3 days of treatment but appeared on day 3 and later. Thus, these effects may likely be related to the sensitisizing capacity of PERKALINK 900 (as indicated in a Guinea Pig Maximisation Test). Treatment of further animals at lower dose levels was was deemed not to provide useful information with regard to systemic toxicity.

Any other information on results incl. tables

Based on the acute dermal toxicity study (LD50 > 2000 mg/kg bw), a 5-day dermal range-finding study was carried out with 1000 and 300 mg/kg bw/day. This resulted in severe skin damage with local or generalised erythema, necrosis and scab formation. Renewed range finding with 100 and 30 mg/kg bw/day gave identical results, viz. 30 mg/kg bw induced severe local effects appearing on days 3, 4 and 5.

Applicant's summary and conclusion

Executive summary:

In a 5 day dermal range-finding study corrosive effects were observed at the 1000 and 300 mg/kg dose level. Therefore, a new pilot study was conducted using dose levels of 30 and 100 mg/kg body weight/day at the maximized dose volume of 7.5 ml/kg body weight. Again severe local effects were noted. As in the first pilot study no skin effects were seen on the first 2-3 days of treatment but appeared on day 3 and later. Thus, these effects may likely be related to the sensitisizing capacity of PERKALINK 900 (as indicated in a Guinea Pig Maximisation Test). Treatment of further animals at lower dose levels was was deemed not to provide useful information with regard to systemic toxicity.