Fatty acids, linseed-oil, reaction products with 2-amino-2-(hydroxymethyl)-1,3-propanediol and formaldehyde

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-07-21 to 2016-10-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

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:

Fatty acids, linseed-oil, reaction products with 2-amino-2-(hydroxymethyl)-1,3-propanediol and formaldehyde

EC Number:

279-510-2

EC Name:

Fatty acids, linseed-oil, reaction products with 2-amino-2-(hydroxymethyl)-1,3-propanediol and formaldehyde

Cas Number:

80584-99-2

Molecular formula:

n.a.

IUPAC Name:

Fatty acids, linseed-oil, reaction products with 2-amino-2-(hydroxymethyl)-1,3-propanediol and formaldehyde

Test material form:

liquid

Details on test material:

- Batch No: 3300081
- Physical state: liquid
- Colour: colourless to yellow
- Purity: 100 %
- Expiry date: 2018-05-16
- Storage conditions: Room temperature (20 ± 5 °C), keep away from light

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Velaz Prague, Czech Republic
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 185-200g
- Fasting period before study: food was withheld over-night (but not water).
- Housing: plastic cages suspended on stainless steel racks, up to 3 animals per cage.
- Diet (e.g. ad libitum): laboratory food ssniff (Spezialdiäten GmbH, Germany), in recommended doses each day approximately at the same time.
- Water (e.g. ad libitum): tap water for human consumption (unlimited), quality of drinking water is periodical analysed.
- Acclimation period: 5 days prior to the start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4 ± 0.4 °C
- Humidity (%): 55.3 ± 4.0%
- Air changes (per hr): central air conditioning
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Olive oil is a standard vehicle according to OECD TG 423.
- Lot/batch no. (if required): L52897, Expiry Date: 04/2017

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Available information indicated that the test item is likely to be nontoxic with regard to acute toxicity.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 females per step, 2 steps performed

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observation was made immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Thereafter, the animals were observed for clinical signs daily. Weighing was performed shortly before administration of the test item and weekly thereafter.
- Necropsy of survivors performed: yes, all test animals were subjected to gross necropsy. Full, detailed gross necropsy included examination of external surface of the body, all orifices, and cranial, thoracic and abdominal cavities and their contents.
- Other examinations performed: Clinical observations included changes in skin, fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Statistics:

N.A.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the study.

Clinical signs:

other: No change of health and no negative reactions were registered. Animals lived through observation period without signs of intoxication.

Gross pathology:

No macroscopically findings were noticed, during necropsy.

Other findings:

N.A.

Any other information on results incl. tables

Table 1: Body Weight

Sex	Dose	ID	Body Weight(g)			Body Weight Difference (g)
			Initial	Week1	Week2	Week 1 -Initial	Week 2 -Initial	Week 2 - Week1
♀	2000 mg/kg	1	200	220	225	20	25	5
		2	190	220	230	30	40	10
		3	195	220	235	25	40	15
		4	190	220	250	30	60	30
		5	185	230	235	45	50	5
		6	185	200	230	15	45	30

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study in rats according to OECD 423, no adverse effects were observed for the test item VOELOFA Monomer at the limit dose of 2000 mg/kg bw. Hence, the LD50 value is determined to be greater than 2000 mg/kg bw.

Executive summary:

In an acute ora ltoxicity study (acute toxic class method, OECD 423), two groups of fasted, 8-12 weeks old female Wistar rats (3 rats/ group) were given a single oral dose of  VOELOFA Monomer (100% purity) in olive oil at the limit dose of 2000 mg/kg bw and were observed for 14 days.

 

Oral LD₅₀Females =  > 2000 mg/kg bw

 

No mortality was observed during the study. Animals lived through observation period without signs of intoxication. Throughout the 14-day observation period, no body weight losses were observed. At necropsy, no macroscopically findings were noticed. Based on the results from this study, the oral LD50 in rats is considered to be greater than 2000 mg/kg bw.