Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014-03-04 to 2014-03-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted: 17th December 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
of 30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90
- Age at study initiation: Young adult rats, 11 weeks old in group 1 and 2
- Weight at study initiation: 216-229 g
- Fasting period before study: The day before treatment the animals were fasted. The food but not water was withheld overnight.
- Housing: 3 animals/sex/cage; Type II polypropylene/polycarbonate; rat type cages with a solid floor, stainless steel wire covers and self-feeding baskets.
- Diet: ssniff® SM R/M-Z+H complete diet produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum.
- Water: Animals received tap water from watering bottles ad libitum.
- Acclimation period: 26 days in first step and 27 days in second step

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 10-15 air exchanges/hour by central air-condition system.
- Photoperiod: Artificial light, from 6 am. to 6 pm.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Helianthi annui oleum raffinatum (sunflower oil)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 208.4 mg/mL
- Justification for choice of vehicle: Test item soluble in vehicle; Vehicle establised as agreeable vehicle for AOT test
- Lot/batch no.: 1305-4630

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: Starting dose was selected on the basis of the available information about the test item.
Doses:
2084 mg/kg bw
No. of animals per sex per dose:
6 animals per dose (3 animals per step) females only
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Morbidity and mortality: Twice daily at the beginning and end of the working day.
Clinical Observations: After dosing once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h, after the treatment and once per day for 14 days thereafter.
Body weight: On day 0 (shortly before the treatment), on day 7 and on day 15 on all animals with a precision of 1 g.
- Necropsy of survivors performed: Yes, the appearance of the tissues and organs were observed.
Statistics:
None

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 084 mg/kg bw
Based on:
test mat.
Mortality:
The test item did not induce mortality following a single oral administration to female rats at a dose of 2084 mg/kg bw . All female rats survived the performed treatment until the end of the 14-day observation period.

Clinical signs:
In group 1 treated with 2084 mg/kg bw of the test item clinical sign of reaction comprised of diarrhoea (10 cases of 57 observations). This symptom (score +1; +2) was observed in all animals. It was detected on the treatment day between 1 and 4 hours after the treatment.

In group 2 treated with 2084 mg/kg bw of the test item clinical sign of reaction comprised of diarrhoea (9 cases of 57 observations). This symptom (score +1; +2 ) was observed in all animals. It was detected on the treatment day between 1 and 3 hours after the treatment.
Body weight:
The mean body weight of the other animals corresponded to their species and age throughout the study.
Gross pathology:
All animals treated with 2084 mg/kg bw of test item survived until the scheduled necropsy on Day 15.
Moderate hydrometra was observed in one female of the group 1. Hydrometra is a physiological finding and connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In the acute oral toxicity study with the test item SIKA Hardener AI in rats the determined LD50 is greater than 2084 mg/kg bw (LD50 ≥ 2084 mg/kg bw).
Executive summary:

In this acute oral toxicity study, two groups of female rats (Crl(WI)Br) were given a single oral dose of the test item SIKA Hardener AI at a concentration of 2084 mg/kg bw. The starting dose was selected on the basis of the available information about the test item.

The acute toxic class method was carried out involving a stepwise procedure with the use of 2084 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2084 mg/kg bw dose level.

Therefore, treatment with 2084 mg/kg bw was repeated on further three female rats. Again, no animal died in the second step, thus no further testing was required. The stopping criteria of Annex 2d of OECD Guideline No. 423 were met.

Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day after the treatment.

 

Lethality, Clinical symptoms and Body weight:

No lethality was noted following oral administration of a single dose of 2084 mg/kg bw.

In the first step, disturbance of the autonomic functions (diarrhoea) was observed in animals on the treatment day.

In the second step, disturbance of the autonomic functions (diarrhoea) was observed in animals on the treatment day.

The body weight development was normal in all animals.

 

Gross pathology:

Altogether 6 animals were subjected to scheduled sacrifice during the study.

All organs of the animals treated with 2084 mg/kg bw dose proved to be free of treatment related gross pathological changes.

 

Evaluation:

The method used is not intended to allow for the calculation of a precise LD50 value. However, for this acute oral toxicity study with the test item SIKA Hardener AI in rats the determined LD50 is greater than 2084 mg/kg bw (LD50 ≥ 2084 mg/kg bw).