N-[3-({[2,2-dimethyl-3-(morpholin-4-yl)propylidene]amino}methyl)-3,5,5-trimethylcyclohexyl]-2,2-dimethyl-3-(morpholin-4-yl)propan-1-imine

Endpoint summary

Description of key information

Sika Hardener MI 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. In an acute dermal toxicity study conducted according to OECD Guideline 402 the dermal toxicity was found 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:

from 2011-04-26 to 2011-07-14

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:

17 December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

30 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

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, Hungary
- 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, if necessary.

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.

Statistics:

NA

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 animals 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 animals died in the second step, too, so the test was finished - the stopping criteria of Annex 2d of OECD Guideline No. 423.

Key result

Sex:

female

Dose descriptor:

discriminating dose

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:

other: 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.

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 MI was found to be greater than 2000 mg/kg bw in rats.

Executive summary:

Sika Hardener MI was tested for acute oral toxicity in study with rats according to OECD Guideline 423. 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 animals 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 animals died in the second 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 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, a 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

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

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:

from 2014-04-09 to 2014-05-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24 th Feb 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

31 May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90, Hungary
- Age at study initiation: young adult rats
- Weight at study initiation: preliminary study: 272 - 290 g (only females), main study: males: 252 - 266 g, females: 251 - 277 g
- Housing: individually in 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 ad libitum
- Acclimation period: 5 days (males) and 110 days (females)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: at least 10 % of the total body surface area
- Type of wrap if used: Sterile gauze pads 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.

REMOVAL OF TEST SUBSTANCE
- Washing: residual item was removed with body temperature water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw both for the preliminary and the main study

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: 1h and 5 h after dosing and then once each day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology

Statistics:

not required

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: The test item caused dermal irritation symptoms as slight erythema in both sexes, between Day 1 and Day 6. Other dermal irritation symptoms as small wounds and crust were recorded in both sexes between Day 5 and Day 13.

Gross pathology:

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

Other findings:

none

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal toxicity dose of Sika Hardener MI was found to be greater than 2000 mg/kg bw in rats.

Executive summary:

An acute dermal toxicity study was performed with test item Sika Hardener MI in Hsd.Brl.Han:WISTrats, 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 Sika Hardener MI 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. The results of the study were summarised as follows: No mortality occurred after the 24-hour dermal exposure to the test item in Hsd.Brl.Han:WIST 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 as slight erythema in both sexes, between Day 1 and Day 6. Other dermal irritation symptom as wound, small wounds and crust was recorded in both sexes between Day 5 and Day 13. Mean body weight development was within the normal range for male animals of this strain and age. The body weight loss was observed in three females on first week and two animals out of them did not regain its original body weight. It could be evaluated as a toxic effect of test item. No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy. In this acute dermal toxicity study with the test item Sika Hardener MI, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Hsd.Brl.Han:WISTrats. 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

Additional information

Acute oral toxicity

Sika Hardener MI was tested for acute oral toxicity in study with rats according to OECD Guideline 423. 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 animals 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 animals died in the second 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 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, a LD50 of greater than 2000 mg/kg bw was determined.

 

Acute dermal toxicity

An acute dermal toxicity study was performed with test item Sika Hardener MI in Hsd.Brl.Han:WISTrats, 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 Sika Hardener MI 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. The results of the study were summarised as follows: No mortality occurred after the 24-hour dermal exposure to the test item in Hsd.Brl.Han:WIST 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 as slight erythema in both sexes, between Day 1 and Day 6. Other dermal irritation symptom as wound, small wounds and crust was recorded in both sexes between Day 5 and Day 13. Mean body weight development was within the normal range for male animals of this strain and age. The body weight loss was observed in three females on first week and two animals out of them did not regain its original body weight. It could be evaluated as a toxic effect of test item. No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy. In this acute dermal toxicity study with the test item Sika Hardener MI, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Hsd.Brl.Han:WISTrats. 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

Based on results obtained in the acute oral toxicity and in the acute dermal toxicity study, SIKA Hardener MI was not classified and labelled for acute dermal or oral toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for tenth time in Regulation (EC) No 2017/776.