Reaction product of propylidynetrimethanol, propoxylated, reaction products with ammonia and 2,2-Dimethyl-3-(4-morpholinyl)propanal

Endpoint summary

Description of key information

For the acute oral toxicity study with the test item in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 2000 mg/kg bw).
For the acute dermal toxicity study with the test item in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 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:

2013-03-05 to 2013-03-21

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.
- Age of animals: Young adult rats, 8 weeks old in group 1 and 2
- Weight at study initiation: 196 - 200 g
- Fasting period before study: the day before treatment
- Housing: 3 animals/sex/cage
- Diet: ssniff® SM R/M-Z+H complete diet, ad libitum
- Water: tap water from watering bottles ad libitum
- Acclimation period: 5 days in first step and 6 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 (hrs dark / hrs light): 12/12, artificial light, from 6 am. to 6 pm.

IN-LIFE DATES: From: 2013-03-05 To: 2013-03-21

Route of administration:

oral: gavage

Vehicle:

other: Helianthi annui oleum raffinatum

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: common vehicle
- Lot/batch no.: 19T3

DOSAGE PREPARATION: Formulations were prepared just before the administration and stirred continuously during the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: No severe acute toxicity was expected.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2x 3 female animals

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of 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
- 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:

not applicable

Preliminary study:

not applicable

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All female rats in step 1 (2000 mg/kg bw dose) survived until the end of the 14-day observation period.
In step 2, one rat dosed at 2000 mg/kg bw SIKA Hardener MTJ died on the treatment day 2 hours after the treatment. The death might be a consequence of systemic toxic effect of the test item.

Clinical signs:

other: In group 1 treated with 2000 mg/kg bw of the test item clinical signs of reaction comprised of decreased activity (14 cases of 57 observations), abnormal gait (6/57), ventral position (7/57), blood around the nose (5/57), piloerection (7/57), decreased gr

Gross pathology:

One rat treated with 2000 mg/kg bw dose of the test item spontaneously died during the study. Five animals treated with 2000 mg/kg bw dose of test item survived until the scheduled necropsy on Day 15.
Slight hydrometra was observed in two females of the group 1 and moderate hydrometra was found in one female of the same group. 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:

not applicable

Summary of lethality

 

Groups	Treatment		Lethality
	Test item	Dose (mg/kg bw)	Females
1	SIKA Hardener MTJ Step 1	2000	0/3
2	SIKA Hardener MTJ Step 2	2000	1/3

 

Interpretation of results:

not classified

Conclusions:

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 Härter MTJ (SIKA Hardener MTJ) in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 2000 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 MTJ at a concentration of 2000 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 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. Therefore, treatment with 2000 mg/kg bw was repeated on further three female rats. Since only one animal died in the second step, no further testing was required. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the treatment day in died animal and on the 15th day after the treatment in survivor animals. Lethality, Clinical symptoms and Body weight: One of six animals treated with 2000 mg/kg bw SIKA Hardener MTJ died on the treatment day 2 hours after the treatment. In the first step, CNS - and emotion symptoms (decreased activity, vocalisation), decreased muscular tension (body-, abdominal-, grip- and limb tone, skin turgor) and disturbances of the autonomic functions (dyspnoea, piloerection, blood around the nose) and coordination (abnormal gait, ventral position) were observed in animals between treatment day and Day 1. In the second step, CNS - and emotion symptoms (decreased activity, tremor, closed eyes) and disturbance of the coordination (ventral position) were observed in animals on the treatment day between 30 min and 1 hour after the treatment. The body weight development was normal in all animals. Gross pathology: Altogether 1 animal died, and 5 animals were sacrificed as scheduled during the study. All organs of the animals treated with 2000 mg/kg bw dose 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 SIKA Hardener MTJ in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 2000 mg/kg bw).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study according to OECD/EU guideline. Reliable without restrictions.

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:

2014-04-09-2014-05-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

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
- Age at study initiation: Young adult rats, females were nulliparous and non-pregnant
- Weight at study initiation: Male: 252 - 264 g, Female: 252 - 278 g
- Housing: During acclimatisation: 3 animals/sex/cage During the study: animals were housed
individually.
- Diet: The animals received ssniff® SM R/M-Z+H complete diet produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany, ad libitum
- Water: Tap Water
- Acclimation period: Male: 5 days, Female: 110 days

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

Vehicle:

other: Helianthi annui oleum raffinatum

Details on dermal exposure:

TEST SITE
- Area of exposure: Back of animals
- % coverage: 10 % of the total body surface area
- Type of wrap used: Sterile gauze pads

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the exposure period, the test item was removed, using body temperature water.
- Time after start of exposure: 24 hours

VEHICLE
- Name: Helianthi annui oleum raffinatum
- Batch no: 1304-4573
- Date of expiry: 22.04.2014

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males
5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Recorded on day 0, on day 7 and on day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: All gross pathological changes were recorded.
- Individual reactions of each animal were recorded at each observation time. Toxic response data are reported by sex and dose level. Nature, severity andduration of clinical observations are described.

Preliminary study:

In a preliminary study no deaths were found at 2000 mg/kg bw dose levels. Therefore, a limit test was performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: No behavioural changes or systemic toxic signs were noted during the study. Dermal irritation symptom as erythema and other sign as wound, small wounds and crust were observed on the treatmnt site. The slight redness (score +1) appeared in all males and f

Gross pathology:

All animals survived until the scheduled necropsy on Day 15. External macroscopic changes as wound and crust were detected on the treated skin surface in one male animal and in one female animal,as well as small wounds and crust were detected in one female animal. No macroscopic alterations due to the systemic toxic effects of the test item were found.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study according to OECD/EU guideline. Reliable without restrictions.

Additional information

Acute toxicity

Oral

In an acute oral toxicity study, two groups of female rats (Crl(WI)Br) were given a single oral dose of the test item SIKA Hardener MTJ at a concentration of 2000 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 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. Therefore, treatment with 2000 mg/kg bw was repeated on further three female rats. Since only one animal died in the second step, no further testing was required. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the treatment day in died animal and on the 15th day after the treatment in survivor animals.

Lethality, Clinical symptoms and Body weight:

One of six animals treated with 2000 mg/kg bw SIKA Hardener MTJ died on the treatment day 2 hours after the treatment. In the first step, CNS - and emotion symptoms (decreased activity, vocalisation), decreased muscular tension (body-, abdominal-, grip- and limb tone, skin turgor) and disturbances of the autonomic functions (dyspnoea, piloerection, blood around the nose) and coordination (abnormal gait, ventral position) were observed in animals between treatment day and Day 1. In the second step, CNS - and emotion symptoms (decreased activity, tremor, closed eyes) and disturbance of the coordination (ventral position) were observed in animals on the treatment day between 30 min and 1 hour after the treatment. The body weight development was normal in all animals.

Gross pathology:

Altogether 1 animal died, and 5 animals were sacrificed as scheduled during the study. All organs of the animals treated with 2000 mg/kg bw dose 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 SIKA Hardener MTJ in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 2000 mg/kg bw).

 

Dermal

An acute dermal toxicity study was performed with the test item in 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. The results of the study were summarised as follows: 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 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 14. Mean body weight development was within the normal range for male animals of this strain and age. Slight body weight loss was observed in three females on first week. It could not 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, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female rats. On the other hand, it is to be noted that the test item caused dermal irritation response on the site of administration.

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

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 not considered to be classified as acute oral toxic as the LD50 is >2000 mg/L, as amended for the fifteenth time in Regulation (EU) No 2020/1182.

 

Acute dermal 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 amended for the fifteenth time in Regulation (EU) No 2020/1182. As a result the substance is not considered to be classified as acute dermal toxic as the LD50 is >2000 mg/L.