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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2012-03-28 to 2013-03-05
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted by a GLP accredited laboratory using OECD Testing Guideline 425. The study was conducted on 6-[(p-Tosyl)amino]hexanoic acid, which is the carboxylic acid component of the registered substance i.e. tosyl salt.

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 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Batch No.: 110526S
Expiry date: 26.05.2013
Purity: 99,24% (taken as 100%)
Instructions for storage: Room temperature, 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:
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 in TECHNIPLAST cages Type 2145 F. The cages measured 480 x 265x 210 mm (floor area 940 cm2). As bedding, sterilized sawdust was used. Two and three animals were housed per cage, respectively.

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

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test substance was administered orally by a stomach tube (gavage). The substance was applied as a suspension in water. The applied volume was 20 ml/ kg body weight per animal. The dose (2000 mg/kg) was given in two fractions over a period of 4 hours. Dosing was performed sequentially: on day 1 three animals were treated and on day 5 two animals were treated.
Doses:
The dose (2000 mg/kg) was given in two fractions over a period of 4 hours. Dosing was performed sequentially: On day 1 three animals were treated and on day 5 two animals were treated. Dosing was done using a suspension of ASC plus in water with 20 ml suspension/kg body weight per rat.
No. of animals per sex per dose:
5 females were treated with one dose
Control animals:
no
Details on study design:
A dose of 2000 mg/kg ASCplus was administered in 2 fractions to 5 female rats using a stomach tube. The animals were caged in a group of 3 and in one of 2 animals. The observation period was 14 days. Prior to the beginning of the study, animals were acclimated for 5 days in their cages. Each rat was individually marked by a code on the tail. The environmetal conditions as well as the mortality, clinical effects and animal health were monitored over the whole test period. At the beginning and at the end of the study the body weight of all animals was measured. Moreover, a necropsy was performed on all animals after termination of the study and the organs were examined macroscopically.
Statistics:
Data recorded during the study were tabulated.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no toxicity observed
Mortality:
No moribund animals were observed within the test period of 14 days.
Clinical signs:
No clinical signs have been detected during and at the end of the exposure period.
Body weight:
All exposed rats showed an increase (same tendency) of the body weight over the 14 days of exposure.
Gross pathology:
No macroscopically detected pathological changes in organs or tissues of the animals were observed.
Other findings:
None of the animals showed any toxicity symptoms or behavioral changes over the whole observation period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance did not cause any symptoms of toxicity after an oral dosage of 2000mg/kg. Therefore, the LD50 was reported as >2000 mg/kg bw/day, and the substance does not require classification as an acute oral toxin according to EU CLP criteria.
Executive summary:

The acute oral toxicity of the test substance was determined in accordance with the OECD Guideline for Testing of Chemicals 425, using the up-and-down procedure. An oral dosage of 2000 mg/kg of the test substance was administered in 2 fractions during 4 hours to 5 female rats. The test article was suspended in water and an administration volume of 20 ml/kg bw was used. During the observation period of 14 days environmental conditions as well as the animal health, clinical effects, mortality and body weight were monitored. At termination of the study, a necropsy was performed with all animals and the major organs were examined macroscopically. The test substance did not cause any symptoms of toxicity after an oral dosage of 2000mg/kg. Therefore, the LD50 was reported as >2000 mg/kg bw/day, and the substance does not require classification as an acute oral 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-[(p-Tosyl)amino]hexanoic acid by simple neutralisation with triethanolamine (TEA). Other than ionization of the carboxylic acid group, the 6-[(p-Tosyl)amino]hexanoic acid remains chemically unchanged upon salt formation. In water, the acid and amine components of 6-[(p-Tosyl)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. The pKa of the carboxylic acid group in 6-[(p-Tosyl)amino]hexanoic acid (pKa = 4.90) is the same in the free acid as it is in the TEA salt. As a result, 6-[(p-Tosyl)amino]hexanoic acid will respond to changes of pH in the same way whether it is in the salt form or as the parent carboxylic acid and hence it’s bioavailability will be the same.