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

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 3

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

Test material

Test material information

Constituent 1

Reference substance name:

(3E)-12-[(2-{2-[(E)-[2,2-dimethyl-3-(morpholin-4-yl)propylidene]amino]propoxy}propoxy)methyl]-12-ethyl-2,2,5,8-tetramethyl-1-(morpholin-4-yl)-7,10,14-trioxa-4-azaheptadec-3-en-16-ol; 4-[(3E,20E)-12-[(2-{2-[(E)-[2,2-dimethyl-3-(morpholin-4-yl)propylidene]amino]propoxy}propoxy)methyl]-12-ethyl-2,2,5,8,16,19,22,22-octamethyl-23-(morpholin-4-yl)-7,10,14,17-tetraoxa-4,20-diazatricosa-3,20-dien-1-yl]morpholine; 4-[(3E,20E)-12-ethyl-2,2,5,8,16,19,22,22-octamethyl-23-(morpholin-4-yl)-7,10,14,17-tetraoxa-4,20-diazatricosa-3,20-dien-1-yl]morpholine

EC Number:

700-879-7

Cas Number:

1379822-00-0

Molecular formula:

NA: UVCB substance

IUPAC Name:

(3E)-12-[(2-{2-[(E)-[2,2-dimethyl-3-(morpholin-4-yl)propylidene]amino]propoxy}propoxy)methyl]-12-ethyl-2,2,5,8-tetramethyl-1-(morpholin-4-yl)-7,10,14-trioxa-4-azaheptadec-3-en-16-ol; 4-[(3E,20E)-12-[(2-{2-[(E)-[2,2-dimethyl-3-(morpholin-4-yl)propylidene]amino]propoxy}propoxy)methyl]-12-ethyl-2,2,5,8,16,19,22,22-octamethyl-23-(morpholin-4-yl)-7,10,14,17-tetraoxa-4,20-diazatricosa-3,20-dien-1-yl]morpholine; 4-[(3E,20E)-12-ethyl-2,2,5,8,16,19,22,22-octamethyl-23-(morpholin-4-yl)-7,10,14,17-tetraoxa-4,20-diazatricosa-3,20-dien-1-yl]morpholine

Test material form:

liquid

Test animals

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

Administration / exposure

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

Results and discussion

Preliminary study:

not applicable

Effect levels

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

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

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).