Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2013-01-07 to 2013-03-08
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study was conducted by a GLP accredited laboratory using OECD Testing Guideline 402. The study was conducted on 6-[(p-tosyl)amino]hexanoic acid, which is the carboxylic acid component of 6-[(p-tosyl)amino]hexanoic acid, compound with 2,2’,2’’-nitrilotriethanol (1:1), a structurally similar substance to the registered substance.

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
Type:
Constituent
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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single dermal administration of 2000 mg/kg bw of the test substance to 5 male and 5 female rats did not cause any sign of systemic toxicity or dermal irritation were observed. The LD50 of the test substance was reported as >2000 mg/kg bw/day, therefore the substance does not require classification as an acute dermal toxin according to EU CLP criteria.
Executive summary:

The dermal toxicity of the test substance to rats was determined in accordance with the OECD Guideline for Testing of Chemicals 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/kg bw of the test substance were applied to 5 female and five male rats in an occlusive way for 24 hours. At the end of the exposure period, any 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 the test substance were observed. The LD50 of the test substance was reported as >2000 mg/kg bw/day, therefore the substance does not require classification as an acute dermal toxin according to EU CLP criteria. The test substance was the carboxylic acid component of the registered substance. Read-across between the tosyl salt carboxylic acid (6 -[(p-tosyl)amino]hexanoic acid) and the registered substance is considered justified as the registered substance is manufactured directly from 6-[methyl(phenylsulphonyl)amino]hexanoic acid by simple neutralisation with triethanolamine (TEA). 6-[methyl(phenylsulphonyl)amino]hexanoic acid and 6-[(p-tosyl)amino]hexanoic acid are structural isomers. They are the same molecular weight and differ only in the position of a single methyl group. In the former, the methyl group is bound to the nitrogen atom of the sulphonamide linkage whereas in the latter, it resides on the aromatic ring. Other than ionization of the carboxylic acid group, the 6-[methyl(phenylsulphonyl)amino]hexanoic acid remains chemically unchanged upon salt formation. In water, the acid and amine components of 6-[methyl(phenylsulphonyl)amino]hexanoic acid, compound with 2,2’,2’’-nitrilotriethanol (1:1) dissociate completely and behave essentially as independent substances. Since TEA can be considered non-hazardous, it is the acid component of the salt that will have a more significant impact on the outcome of any (eco)toxicological or environmental tests.