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Description of key information

The test item was tested for its acute oral toxicity with rats according to OECD guideline 423. The LD50 was determined to be between 300 mg/kg bw and 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:
2015-24-03 to 2015-05-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90
- Age at study initiation: 8 weeks old
- Weight at study initiation: First step: 183-191 g, second step: 184-187g, third step: 176-187 g
- Fasting period before study: The day before treatment the animals were fasted
- Housing: 3 animals/sex/cage
- 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.
The drinking water is periodically analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Copies of the relevant Certificates of Analysis are maintained in Toxi-Coop Zrt.’s archive.
- Acclimation period: 5 days in first step, 6 days in second step and 7 days in third step

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

Route of administration:
oral: gavage
Vehicle:
other: Helianthi annui oleum raffinatum
Details on oral exposure:
VEHICLE
- Concentration in vehicle: All doses were formulated in the vehicle. Concentration of formulations were adjusted to maintain a treatment volume of 10 mL/kg bw. At starting, the test item was applied in a concentration of 200 mg/mL. The further concentrations were 30 mg/mL, 5 mg/mL and 0.5 mg/mL, if necessary.
- Justification for choice of vehicle: Common vehicle
- Lot/batch no. : 1410-5159

CLASS METHOD
- Rationale for the selection of the starting dose: No severe acute toxicity was expected.
Doses:
2000 mg/kg bw, 300 mg/kg bw
No. of animals per sex per dose:
9 female rats in total
3 females per step (3 x 200 mg/kg bw, 6 x 300 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Mortality: twice daily at the beginning and end of the working day
Clinical observations: 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, on day 7 and on 15
- Frequency of weighing: on day 0 (shortly before the treatment), on day 7 and on day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
NA
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All female rats dosed at 2000 mg/kg SIKA Hardener LPP (SIKA Härter LPP) died during the study. One animal died on the treatment day 2 hours after the treatment and two animals died 3 hours after the treatment, respectively.
No death occurred at 300 mg/kg single oral dose of the test item. All rats in step 2 and step 3 survived until the end of the 14-day observation period.
Clinical signs:
In group 1 treated with 2000 mg/kg bw However, red coloured urine was found in all animals on the treatment day between 1 and 2 hours after the treatment. This symptom was not related the test item toxic effect, it was connected with physical property of test item as brownish orange colour. dose clinical sign of reaction comprised of decreased activity (5 cases out of 8 observations), abnormal gait (2/8), decreased righting reflex (2/8), decreased grip- and limb tone (2/8), decreased body tone (2/8), decreased abdominal tone (1/8), decreased plantary reflex (2/8), cyanosis (2/8) and dyspnoea (1/8). Decreased activity (score -3; -4) was observed in all animals. Abnormal gait (score +3, +4), decreased righting reflex (score -4), decreased grip- and limb tone (score -4), decreased body tone (score -3; -4), decreased plantary reflex (score -4) and cyanosis (score +1; +2) occurred in two animals. Decreased abdominal tone (score -4) was found in one animal. Dyspnoea (score +3) was recorded in one animal. These symptoms were observed on the treatment day between 1 and 2 hours after the treatment and they were connected with the test item toxic effect. No systemic toxic symptoms were observed throughout the 14-day post-treatment period in all animals of group 2 and 3 treated with 300 mg/kg bw. Red coloured urine was observed in all animals on the treatment day between 1 and 4 hours after the treatment.
Body weight:
The body weight and body weight gain data of group 1 (2000 mg/kg bw) could not be evaluated, because all rats died in this group.
In group 2 and 3 (300 mg/kg bw) the mean body weight of the animals corresponded to their species and age throughout the study.
Gross pathology:
All rats treated with 2000 mg/kg bw dose of the test item spontaneously died during the study. All animals treated with 300 mg/kg dose of test item survived until the scheduled necropsy on Day 15. Slight hydrometra was found in two females of the group 3. Hydrometra is 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.
Other findings:
None
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The test item was tested for its acute oral toxicity with rats according to OECD guideline 423. The LD50 was determined to be between 300 mg/kg bw and 2000 mg/kg bw.
Executive summary:

An acute oral toxicity study was carried out using the class method according to OECD guideline 423. The method was conducted using a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. The starting dose was selected on the basis of the available information about the test item. Since three female animals died the test was continued at 300 mg/kg bw dose level on further three female rats. No animal died in the second step at 300 mg/kg bw dose level, three further female rats were treated with the same (300 mg/kg bw) dose.No animal died in the third step, too, so the test was finished, 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 in animals died on the treatment day, as well as 15th day after the treatment in survivor animals.All of three animals treated with 2000 mg/kg bw test item died on the treatment day between 2 and 3 hours after the treatment.No lethality was noted at single oral dose of 300 mg/kg bw. In the first step at a dose level of 2000 mg/kg bw, CNS - and emotion symptom (decreased activity), decreased reflex- and muscular tension (righting- and plantary reflex, body-, abdominal-, grip- and limb tone) and disturbances of the autonomic functions (cyanosis, dyspnoea) and coordination (abnormal gait) were observed in animals on the treatment day between 1 and 2 hours after the treatment. Besides, red coloured urine was detected in animals on the treatment day between 1 and 2 hours after the treatment. This symptom could not be related the test item toxic effect, it was connected with physical property of test item as brownish orange colour. In the second and third step at a dose level of 300 mg/kg bw, red coloured urine was found in animals on the treatment day between 1 and 4 hours after the treatment. The body weight development was normal in all survivor animals. Altogether 3 animals died, and 6 animals were sacrificed scheduled during the study. All organs of all experimental animals proved to be free of treatment related gross pathological changes. 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 in rats the determined LD50 is between 300 and 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
GLP and guideline study

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

An acute oral toxicity study was carried out using the class method according to OECD guideline 423. The method was conducted using a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. The starting dose was selected on the basis of the available information about the test item. Since three female animals died the test was continued at 300 mg/kg bw dose level on further three female rats. No animal died in the second step at 300 mg/kg bw dose level, three further female rats were treated with the same (300 mg/kg bw) dose.No animal died in the third step, too, so the test was finished, 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 in animals died on the treatment day, as well as 15th day after the treatment in survivor animals.All of three animals treated with 2000 mg/kg bw test item died on the treatment day between 2 and 3 hours after the treatment.No lethality was noted at single oral dose of 300 mg/kg bw. In the first step at a dose level of 2000 mg/kg bw, CNS - and emotion symptom (decreased activity), decreased reflex- and muscular tension (righting- and plantary reflex, body-, abdominal-, grip- and limb tone) and disturbances of the autonomic functions (cyanosis, dyspnoea) and coordination (abnormal gait) were observed in animals on the treatment day between 1 and 2 hours after the treatment. Besides, red coloured urine was detected in animals on the treatment day between 1 and 2 hours after the treatment. This symptom could not be related the test item toxic effect, it was connected with physical property of test item as brownish orange colour. In the second and third step at a dose level of 300 mg/kg bw, red coloured urine was found in animals on the treatment day between 1 and 4 hours after the treatment. The body weight development was normal in all survivor animals. Altogether 3 animals died, and 6 animals were sacrificed scheduled during the study. All organs of all experimental animals proved to be free of treatment related gross pathological changes. 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 in rats the determined LD50 is between 300 and 2000 mg/kg bw.

Justification for classification or non-classification

Acute oral toxicity

 

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified as acute oral toxicity category 4, H302.

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