4-Morpholinepropanal, .alpha.,.alpha.-dimethyl-

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).

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

Remarks:

GLP-study according to OECD/EU guideline. This study is considered as scientific acceptable.

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: 193 - 208 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

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred.

Mortality:

The test item did not induce mortality following a single oral administration to female rats at a dose of 2000 mg/kg bw. All female rats survived the performed treatment until the end of the 14-day observation period.

Clinical signs:

other: In group 1 treated with 2000 mg/kg bw of the test item clinical sign of reaction comprised of decreased activity (3 cases of 57 observations). This symptom (score -1) was observed in all animals. It was detected on the treatment day 30 min. after the trea

Gross pathology:

All animals treated with 2000 mg/kg bw 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 group 2. 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.

Summary of lethality

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

 

Interpretation of results:

not classified

Conclusions:

The LD50 was determined to be above 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 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. 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.

No lethality was noted following oral administration of a single dose of 2000 mg/kg bw. In the first step, CNS - and emotion symptom as decreased activity was observed in all animals on the treatment day 30 min after the treatment. In the second step, CNS - and emotion symptom as decreased activity was observed in one animal on the treatment day between 30 min and 1 hour after the treatment. In the other two animals, no clinical symptoms were observed on the day of the treatment and during the 14-day observation period. The body weight development was normal in all animals.

Altogether 6 animals were subjected to scheduled sacrifice 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 Aldehyde M in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 2000 mg/kg bw).

The test item is ranked into classes of the current EU Regulation on classification, labelling and packaging (CLP) (EC) No 1272/2008. According to the current Regulation (EC) No 1272/2008 no classification is required for the test item.

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

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In this acute oral toxicity study, two groups of female rats (Crl(WI)Br) were given a single oral dose of the test item 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. 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.

No lethality was noted following oral administration of a single dose of 2000 mg/kg bw. In the first step, CNS - and emotion symptom as decreased activity was observed in all animals on the treatment day 30 min after the treatment. In the second step, CNS - and emotion symptom as decreased activity was observed in one animal on the treatment day between 30 min and 1 hour after the treatment. In the other two animals, no clinical symptoms were observed on the day of the treatment and during the 14-day observation period. The body weight development was normal in all animals.

Altogether 6 animals were subjected to scheduled sacrifice 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 Aldehyde M in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 2000 mg/kg bw).

The test item is ranked into classes of the current EU Regulation on classification, labelling and packaging (CLP) (EC) No 1272/2008. According to the current Regulation (EC) No 1272/2008 no classification is required for the test item.

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 LD50 was greater than 2000 mg/kg bw. 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) 2019/521.