Registration Dossier

Administrative data

Description of key information

LD50 (dermal and oral) >= 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-03-28 to 2013-03-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well documented and controlled GLP based study
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
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.
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.
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.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance ASC plus did not cause any symptoms of toxicity after an oral dosage of 2000mg/kg. Therefore, the lethal doses are higher than 2000 mg/kg bw..
Executive summary:

The oral toxicity of ASC plus was determined using the up- and down procedure in rats according to the OECD guideline 425.

An oral dosage of 2000 mg/kg of ASC plus 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 ainmals and the major organs were examined macroscopically.

The oral administration of ASC plus did not cause any toxic symptoms at a dosage of 2000 mg/kg bw.

Therefore, the LD 50 of ASC plus is higher than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
LD50 >= 2000 mg/kg bw.
Quality of data: reliable

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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
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
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.
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
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.
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
LD50 >= 2000 mg/kg bw.
Quality of data: reliable

Additional information

Justification for selection of acute toxicity – oral endpoint
GLP-Guideline study, key study

Justification for selection of acute toxicity – dermal endpoint
GLP-Guideline study, key study

Justification for classification or non-classification

According to the criteria for classification, packaging and labelling of dangerous substances and preparations (mixtures) in accordance with the EEC Directives 67/548, 2001/59 and 1999/45, ASC plus must not be classified.

No symbol or risk phrase is required.

In accordance with the Regulation EC No. 1272/2008 on classification, labelling and packaging of substances and mixtures, ASC plus must not be classified.

No signal word, hazard pictogram(s) or hazard statement(s) are required.