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Administrative data

Description of key information

In the acute oral toxicity study with the test item in rats the determined LD50 is greater than 2084 mg/kg bw (LD50 ≥ 2084 mg/kg bw).

In an acute dermal toxicity study with rats the LD50 was determined to be greater than 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:
2014-03-04 to 2014-03-20
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:
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
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.
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
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.
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).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 084 mg/kg bw
Quality of whole database:
GLP and guideline compliant 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:
2016-09-15 to 2016-10-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1998
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:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young adult rats
- Weight at study initiation: males: 267-277 g; females: 225-249 g
- Housing: single housing
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 - 20 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: at least 10 % of the body surface
- Type of wrap if used: sterile gaze pads, adhesive hypoallergenic plaster, semiocclusive wrap

REMOVAL OF TEST SUBSTANCE
- Washing: body temperature water
- Time after start of exposure 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Inspection was made twice daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Preliminary study:
There were no deaths in preliminary study, where doses of 5, 50, 300, and 2000 mg/kg bw were tested.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred after the 24-hour dermal exposure to the test item in Crl(WI) male and female rats during the study.
Clinical signs:
No behavioural changes or systemic toxic signs were noted during the study.
Dermal irritation symptoms as erythema, oedema and other signs as desquamation, wounds and crusting were observed on the treatment site. Very slight (score 1) and/or well defined erythema (score 2) occurred in all males. It was detectable between Day 1 and Day 10. Very slight redness (score 1) was observed in all females between Day 1 and Day 5. Very slight oedema (score 1) was found in two males (No.: 2979, 2983) on Day 4. Wounds, desquamation and crusting were detected in males between Day 4 and Day 9. Wounds and desquamation were recorded in all males and crusting was observed in four males (No.: 2980, 2981, 2982, 2983).
Body weight:
Mean body weight development was within the normal range for male animals of this strain and age. A body weight loss was observed in female No.: 2922 between Day 0 and Day 7. The body weight loss was very slight (approx. 2.4 %).
Gross pathology:
All animals survived until the scheduled necropsy on Day 15.
Internal macroscopic changes were observed. A seminal vesicle atrophy was detected in male animal No.: 2981 on the right side. Ovary cyst was seen in female No.: 2925 on the right side and severely wide section of uterus was detected in same female. These alterations could not be related to the test item toxic effect, but were regarded an individual variation. Most likely the observations are a congenital anomaly.
Moderate hydrometra was observed in female No.: 2926. Hydrometra is a physiological finding and connected to the cycle of the animal.
No macroscopic alterations due to the systemic toxic effects of the test item were found.
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 Crl(WI) male and female rats. According to Regulation (EC) No 1272/2008 and UN GHS, the test item has not been classified into any category.
On the other hand, it is to be noted that the test item caused dermal irritation response on the site of administration.
Executive summary:

An acute dermal toxicity study was performed with test item in Crl(WI) rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200.

A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to the test item at 2000 mg/kg bw by dermal route. The test item was applied in undiluted form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred after the 24-hour dermal exposure to the test item in male and female rats during the study.

Neither male nor female animals treated with 2000 mg/kg bw of the test item showed behavioural changes and no systemic toxic signs were noted during the study. The test item caused dermal irritation symptoms in both sexes. Very slight and well defined erythema was observed in males between Day 1 and Day 10 and very slight erythema was found in females between Day 1 and Day 5. Erythema occurred in all animals. Very slight oedema was recorded in two males on Day 4. Other dermal irritation symptoms as desquamation, wounds and crusting occurred in four males between Day 4 and Day 9.

Mean body weight development was within the normal range for male animals of this strain and age. Slight body weight loss was observed in one female on first week. It was not evaluated as a toxic effect of the test item.

No macroscopic alterations of organs and tissues referred to a systemic toxic effect of the test item were seen during the necropsy.

In this acute dermal toxicity study with the test item, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in Crl(WI) male and female rats. According to Regulation (EC) No 1272/2008 and UN GHS, the test item has not been classified into any category.

On the other hand, it is to be noted that the test item caused dermal irritation response on the site of administration. 

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

Additional information

Acute oral toxicity

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).

Acute dermal toxicity:

An acute dermal toxicity study was performed with test item in Crl(WI) rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200.

A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to the test item at 2000 mg/kg bw by dermal route. The test item was applied in undiluted form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

No mortality occurred after the 24-hour dermal exposure to the test item in male and female rats during the study.

Neither male nor female animals treated with 2000 mg/kg bw of the test item showed behavioural changes and no systemic toxic signs were noted during the study. The test item caused dermal irritation symptoms in both sexes. Very slight and well defined erythema was observed in males between Day 1 and Day 10 and very slight erythema was found in females between Day 1 and Day 5. Erythema occurred in all animals. Very slight oedema was recorded in two males on Day 4. Other dermal irritation symptoms as desquamation, wounds and crusting occurred in four males between Day 4 and Day 9.

Mean body weight development was within the normal range for male animals of this strain and age. Slight body weight loss was observed in one female on first week. It was not evaluated as a toxic effect of the test item.

No macroscopic alterations of organs and tissues referred to a systemic toxic effect of the test item were seen during the necropsy.

In this acute dermal toxicity study with the test item, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in Crl(WI) male and female rats. According to Regulation (EC) No 1272/2008 and UN GHS, the test item has not been classified into any category.

On the other hand, it is to be noted that the test item caused dermal irritation response on the site of administration. 

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. Based on available data on acute toxicity, the test item is not classified as acute oral or dermal toxic according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighth time in Regulation (EU) No 2016/918.