Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-01-07 to 2013-03-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well documented and controlled GLP based study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Name of test material (as cited in study report): ASC plus
Chemical name: 6-[[(4-methylphenyl)sulfonyl]amino]hexanoic acid
Batch No.: 110526S
Expiry date: 26.05.2013
Purity: 99,24% (taken as 100%)
Instructions for storage: at room temperature, in tighly closed container, cool, dry, only in original container
State of material: crystalline, damp, not dusty
Colour: white
Odour: odourless

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Strain: Rat Wistar SPF Charles River Germany D- 97633 Sulzfeld- Facility,
Species: Rattus norvegicus ssp.alba

Environmental conditions were monitored and recorded continuously over the study. The temperature in the animal room was in-between 20°C and 24°C and the relative humidity was in-between 40% and 70% . A 12/12h light/dark cycle was set.

During the study, the study rats were housed individually in TECHNIPLAST cages Type 1284L. The cages measured 365 x 207 x 140 mm (floor area 530 cm2). As bedding, sterilized sawdust was used.

Diet and water:
For feeding, a standard pelleted diet (M3) of monitored quality was used. Potable water from the local mains of monitored quality was supplied ad libitum. Water bottels were changed daily.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
The test item was applied dermal as a paste with 'aqua pro injectione'. The test substance was applied uniformly over an area of 6-10 cm² and it was held in contact with the skin with a porous gauze dressing and non-irritating tape for throughout the 24 hour exposure period. Further, the test site was covered with a adhesive plaster to retain the gauze dressing and ensure that the animals did not ingest the test substance. The fur was removed from the dorsal area of the trunk by clipping 24 hours before the application of the test article. At the end of the exposure period, residual test substance was removed using water.
Duration of exposure:
The animals were observed for a period of 14 days after substance application.
Doses:
As no estimate of the substance`s lethality was available, the initial dosing was 2000 mg/kg (limit test), which was applied to 6-10 cm2 area of skin. Untreated skin areas were used as controls.
No. of animals per sex per dose:
Five animals per dose and sex were used.
Control animals:
no
Details on study design:
Five male rats and five female rats were individually housed in cages and exposed dermally to a limit dose of 2000 mg/kg ASC plus for 14 days. Prior to the study, animals were acclimated for 5 days and the health status such as the body weight was constantly observed. Each rat was individually marked by a code on the tail. Exposure was done on two different days: day 1: 3 males and 3 females, day 2: 2 males and 2females. Bodyweights and clinical signs were monitored during the study. The body weights are reported on day 7 and day 14 after start of the exposure. The animals were sacrificedat the end of the study.
Statistics:
Data were summarized in tabular form

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no effects at limit dose of 2000 mg/kg bw.
Mortality:
There were no moribund animals.
Clinical signs:
The animals showed no dermal lesions, no erythema and no oedema. (No erythema=0, No oedema=0)
Body weight:
All exposed rats showed an increase (same tendency) of the body weight over the 14 days of exposure.
Gross pathology:
A necropsy was performed on all animals at study termination and the mayor organs were macroscopically examined. No macroscopically detected pathological changes in organs or tissues of the animals were observed.
Other findings:
No animal indicated any symptoms of toxicity during the whole observation period. No behavioral and clinical signs were observed.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single dermal administration of 2000 mg ASC plus/kg bw. to 5 male amd 5 female rats did not cause any sign of systemic toxicity.
Also no signs of dermal irritation were observed. The LD 50 of ASC plus after dermal application is higher than 2000 mg/kg.
Executive summary:

The dermal toxicity of ASC plus to rats was studied according to OECD guideline 402.

By clipping 24 hours before the application of the test article the fur was removed from the dorsal area of the trunk of the animals.

The test article was moistured with aqua p.i. and 2000 mg ASC plus/kg bw. were applied to 5 female and five male rats in an occlusive way for 24 hours. At the end of the exposure period, residual test substance was removed using water.

During the observation period of 14 days, clinical signs and bodyweight were monitored.

No signs of systemic toxicity and no signs of dermal irritation of ASC plus have been observed. The LD 50 of ASC plus after dermal application is higher than 2000 mg/kg.