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Administrative data

Description of key information

The test item was tested for acute oral toxicity in study with rats according to OECD Guideline 423 (Acute toxic class method). The study revealed an acute oral toxicity greater than 2000 mg/kg bw in rats.

The test item was tested for acute dermal toxicity in study with rats according to OECD Guideline 402. The study revealed an acute dermal toxicity greater than 2000 mg/kg bw in female rats.

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:
from 2011-04-08 to 2011-07-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
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
Specific details on test material used for the study:
- Batch no.: 10191-AKm
- Purity. 100.5% (aldimine titration)
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 rat, 8 - 12 weeks old
- Weight at study initiation: The weight variation in animals involved in the study will not exceed ± 20 % of the mean weight
- Fasting period before study: 24 hours
- Housing: 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: tap water from watering bottles ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 % Relative Humidity
- Air changes: 8 - 12 air exchanges/hour by central air-condition system.
- Photoperiod: Artificial light, from 6 a.m. to 6 p.m.

IN-LIFE DATES: From: 28 April 2011 To: 19 May 2011
Route of administration:
oral: gavage
Vehicle:
other: Helianthi annui oleum raffinatum
Details on oral exposure:
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.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
A single oral administration - followed by a fourteen-day observation period - was performed by gavage. The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.
Preliminary study:
The acute toxic class method (OECD Guideline No. 423) was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished. The stopping criteria of Annex 2d of OECD Guideline No. 423 were fulfilled.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No lethality was noted at single oral dose of 2000 mg/kg bw.
Clinical signs:
In first and second step, no clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal.
Body weight:
The body weight will be recorded on day 0 (shortly before the treatment), at day 7 and at day 15 on all animals with a precision of 1 g. The body weight development was undisturbed in all animals.
Gross pathology:
All animals survived until the scheduled autopsy on Day 15. All organs of all experimental animals proved to be free of treatment related gross pathological changes.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral toxicity dose of SIKA Hardener MH was found to be greater than 2000 mg/kg bw in rats.
Executive summary:

SIKA Hardener MH was tested for acute oral toxicity in study with rats according to OECD Guideline 423 (Acute toxic class method). The acute toxic class method (OECD Guideline No. 423) was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 was 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.

No lethality was noted at single oral dose of 2000 mg/kg bw. In first and second step, no clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal.

The body weight development was undisturbed in all animals. All animals survived until the scheduled autopsy on Day 15. All organs of all experimental animals proved to be free of treatment related gross pathological changes. Thus, an LD50 of greater than 2000 mg/kg bw was determined.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 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

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2019-07-01 to 2019-09-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
2017
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: I1900071-19158-AKM
- Purity: 99.8 % (aldimine group contents via acid titration)
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9-11 weeks (range-finding); 10-11 weeks (main study)
- Weight at study initiation: 215-228 g (range-finding; 218-228 g (main study)
- Fasting period before study: no
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 °C
- Humidity: 30-70 %
- Air changes: > 10 per hr
- Photoperiod: 12 / 12 hrs dark / hrs light
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: 10
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats. These gauzes were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was wrapped with semi-occlusive plastic wrap for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing: yes, by body warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 200, 1000 and 2000 mg/kg bw
- Constant volume or concentration used: no (the test item was applied in undiluted form)
Duration of exposure:
24 h
Doses:
200, 1000, 2000 mg/kg bw
No. of animals per sex per dose:
range-finding study: 1 female animal per dose
main study: 2 female animals per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually 30 minutes, 2 h, 4 h and 6 h after dosing, and once each day for 14 days thereafter for systemic toxic signs. The body weight was recorded on day 0 (shortly before the treatment) on day 7 and on day 15 before sacrifice on all animals with a precision of 1 g in the main study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Preliminary study:
range finding study:
No mortality occurred after the 24-hour dermal exposure to Sika Hardener MH in three female rats during the range-finding study. The initial dose was 200 mg/kg bw. The other doses were as 1000 mg/kg bw and 2000 mg/kg bw, respectively.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
In the main study, the dose of 2000 mg/kg bw was applied to two further animals. There was no mortality in main study, too.
Clinical signs:
No behavioural changes or systemic toxic signs were noted during the study.
Dermal irritation symptoms as erythema and other signs as dry skin surface, wound, small wound/s and crust were observed on the treatment site.
200 mg/kg bw
There was not any dermal irritation sign.
1000 mg/kg bw
Very slight erythema (score 1) was observed in animal No.: 5227 on Day 1.
2000 mg/kg bw
Animal No.: 5228: Very slight erythema (score 1) was observed between Day 1 and Day 4. Well defined erythema (score 2) was recorded between Day 5 and Day 14. Dry skin surface occurred between Day 2 and Day 4. Small wounds were detected between Day 5 and Day 11. Crust was found between Day 5 and Day 14. Wound was observed between Day 12 and Day 14.
Animal No.: 5229: Well defined erythema (score 2) was recorded between Day 1 and Day 3. Very slight erythema (score 1) was observed between Day 4 and Day 14. Wound was observed between Day 3 and Day 14. Crust was found between Day 3 and Day 14.
Animal No.: 5230: Well defined erythema (score 2) was recorded between Day 1 and Day 2. Very slight erythema (score 1) was observed between Day 3 and Day 14. Small wounds were detected on Day 2.Wound was observed between Day 3 and Day 14. Crust was found between Day 4 and Day 14.
Body weight:
Mean body weight development was within the normal range for animals of this strain and age, except one case. A body weight loss was observed in animal No.: 5227 treated with 1000 mg/kg bw test item between Day 0 and Day 7. The body weight loss was very slight (approx. 0.5 %). This body weight loss was below 10 % and the body weight of the animal exceeded the original body weight by the end of study, thus it can be evaluated as an individual variation without toxicological meaning.
Gross pathology:
All animals survived until the scheduled necropsy on Day 15.
External macroscopic changes were observed connected with local irritation symptoms. Erythema, wound and crust were observed on the treated skin surface in all animals of 2000 mg/kg bw dose.
Severe hydrometra was observed in animal No.: 5226 of 200 mg/kg bw dose and in animal No.: 5227 of 1000 mg/kg bw dose. Besides, moderate hydrometra was found in animal No.: 5230 of 2000 mg/kg bw dose. Hydrometra is a physiological finding and connected to the oestrus cycle of the animal.
No macroscopic alterations related to the systemic toxic effects of the test item were found.
Other findings:
- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: no

Table 1 Summary of lethality (Range-finding and main study)

Test Item Dose mg/kg bw

Lethality (Females)

200

0/1

1000

0/1

2000

0/3

Interpretation of results:
GHS criteria not met
Conclusions:
In this acute dermal toxicity study with the test item, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in Han:WIST female rats.
Executive summary:

An acute dermal toxicity study was performed with test item in Han:WIST rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200. At first, the range-finding study was performed. The starting dose was 200 mg/kg bw using one animal. The other doses were 1000 and 2000 mg/kg bw applying one animal, each. No death was observed. Therefore, 2000 mg/kg bw dose was used in the main study. The test item was applied to three animals in original form, i. e. without vehicle,and left in contact with the skin for 24 hours, followed by a 14-day observation period. No death was observed in the 2000 mg/kg bw dose group in the main study. Animals treated with 2000 mg/kg bw of the test item did not show behavioral changes and no signs of systemic toxicity were noted during the study. The test item caused dermal irritation symptoms as well as defined or slight erythema between Day 1 and Day 14. Other dermal irritation symptoms as dry skin, small wound, crust and wound were recorded between Day 2 and Day 14. Mean body weight development was within the normal range for animals of this strain and age in the main study. No macroscopic alterations of organs and tissues referring to systemic toxicity of the test item were seen during the necropsy. It is to be noted that the test item caused dermal irritation response on the site of administration.

In this acute dermal toxicity study with the test item, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in Han:WIST female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP and guideline conform study.

Additional information

Acute oral toxicity:

SIKA Hardener MH was tested for acute oral toxicity in study with rats according to OECD Guideline 423 (Acute toxic class method).The acute toxic class method (OECD Guideline No. 423) was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 was 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.

No lethality was noted at single oral dose of 2000 mg/kg bw. In first and second step, no clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal.

The body weight development was undisturbed in all animals. All animals survived until the scheduled autopsy on Day 15. All organs of all experimental animals proved to be free of treatment related gross pathological changes.Thus, an LD50 of greater than 2000 mg/kg bw was determined.

Acute dermal toxicity:

An acute dermal toxicity study was performed with test item in Han:WIST rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200.At first, the range-finding study was performed. The starting dose was 200 mg/kg bw using one animal. The other doses were 1000 and 2000 mg/kg bw applying one animal, each. No death was observed. Therefore, 2000 mg/kg bw dose was used in the main study.The test item was applied to three animals in original form, i. e. without vehicle,and left in contact with the skin for 24 hours, followed by a 14-day observation period. No death was observed in the 2000 mg/kg bw dose group in the main study.Animals treated with 2000 mg/kg bw of the test item did not show behavioral changes and no signs of systemic toxicity were noted during the study. The test item caused dermal irritation symptoms as well as defined or slight erythema between Day 1 and Day 14. Other dermal irritation symptoms as dry skin, small wound, crust and wound were recorded between Day 2 and Day 14.Mean body weight development was within the normal range for animals of this strain and age in the main study.No macroscopic alterations of organs and tissues referring to systemic toxicity of the test item were seen during the necropsy.It is to be noted that the test item caused dermal irritation response on the site of administration.In this acute dermal toxicity study with the test item, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in Han:WIST female rats.

Justification for classification or non-classification

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. The acute oral and dermal LD50 was greater than 2000 mg/kg bw, respectively. As a result the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No. 1272/2008, as amended for the twelfth time in Regulation (EU) No. 2019/521.