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

Endpoint summary

Description of key information

In an acute dermal toxicity study according to OECD 402, groups of young adult Wister rats (5 male/ 5 female) were dermally exposed to VOELOFA Monomer (100% purity) for 4 hours at a limit dose of 2000 mg/kg bw and were observed for 14 days. Based on the results, the target substance does not require classification for acute toxicity according to CLP criteria. In an acute oral toxicity study according to 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) at the limit dose of 2000 mg/kg bw and were observed for 14 days. Based on the results, the target substance does not require classification for acute toxicity according to CLP criteria.

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:

2016-07-21 to 2016-10-17

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)

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: 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

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.

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.

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Guideline study

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:

2016-07-22 to 2016-10-17

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:

adopted, 24 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)

Version / remarks:

Proposal for a New Draft Guideline 434, May 2004

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: Velaz Prague, Czech Republic
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: females 190-210 g; males: 220-260 g
- Fasting period before study: no
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, up to 2-3 animals per cage, males and females separately in a room equipped with central air-conditioning. The sanitation was performed according to the standard operation procedures. Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany

- Diet (e.g. ad libitum): laboratory food ssniff (ssniff Spezialdiäten GmbH), offered in recommended doses each day approximately at the same time
- Water (e.g. ad libitum): unlimited supply of tap water for human consumption (periodical analysis of the quality, including microbiological control)
- Acclimation period: at least 5 days prior to the start of treatment (according to standard operation procedures)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4 ± 0.4 °C
- Humidity (%): 55.3 ± 4%.
- Air changes (per hr): central air-conditioning
- Photoperiod (hrs dark / hrs light): 12-hour light/ 12-hour dark cycle

Type of coverage:

semiocclusive

Vehicle:

olive oil

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10%
- Type of wrap if used: Cosmopor E and a semi-occlusive dressing with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): removing using lukewarm water
- Time after start of exposure: 24h (at the end of the exposure period of 24 h)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): limit dose of 2000 mg/kg body weight (single application)
- For solids, paste formed: no

VEHICLE
Olive Oil (Oleificio Luca, Italy, lot no.: L52897, expiry date 04/2017) is a standard vehicle according to OECD TG 423.

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 0.5, 1, 2, and 4 hours after application and daily thereafter
- Frequency of weighing: determined shortly before the test item was applied and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Observations included changes in skin and fur, eyes and mucous membranes, and also 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.

Key result

Sex:

male/female

Dose descriptor:

LD50 cut-off

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality was observed during the study.

Clinical signs:

other: Animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were registered.

Gross pathology:

All animals (5 females and 5 males) were necropsied. During necropsy, no macroscopic changes were noticed.

Table 1: Body Weight

Sex	Dose	ID	Body Weight (g)			Body Weight Difference (g)
			Initial	Week 1	Week 2	Week 1 -Initial	Week 2 -Initial	Week 2 - Week 1
♀	2000 mg/kg	1	200	220	245	20	45	25
		2	190	200	215	10	25	15
		3	210	220	240	10	30	20
		4	210	230	240	20	30	10
		5	200	230	240	30	40	10
♂	2000 mg/kg	6	260	330	370	70	110	40
		7	250	300	340	50	90	40
		8	240	300	340	60	100	40
		9	250	320	370	70	120	50
		10	220	260	305	40	85	45

   

Interpretation of results:

GHS criteria not met

Conclusions:

In conclusion, in an acute dermal toxicity study according to OECD 402 and OECD Guidline Draft 434, single dermal application of the test item VOELOFA Monomer to rats at a limit dose of 2000 mg/kg bw was associated with no mortality. Animals lived through observation period without signs of intoxication. Neither change of health nor negative reactions were registered.

Executive summary:

In an acute dermal toxicity study according to OECD 402, groups of young adult Wister rats (5 male/ 5 female) were dermally exposed to VOELOFA Monomer (100% purity) in olive oil for 4 hours to 10% of the total body surface area at a dose of 2000 mg/kg bw. Animals then were observed for 14 days.

 

Dermal LD₅₀ Males >2000 mg/kg bw

                      Females > 2000 mg/kg bw

 

The study was performed as a limit test. No mortality occurred during the test period. There were no treatment related clinical signs, necropsy findings or changes in body weight.

According to the present study, VOELOFA Monomer does not require classification for acute toxicity according to CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Guideline study

Additional information

VOELOFA Monomer (100% purity) was tested negative for acute dermal toxicity in a study conducted according to OECD Guideline 402. No mortality occurred during the test period. There were no treatment related clinical signs, necropsy findings or changes in body weight.

VOELOFA Monomer (100% purity) was tested negative for acute oral toxicity in a study conducted according to OECD Guideline 423. No mortality occurred during the test period. There were no treatment related clinical signs, necropsy findings or changes in body weight.

Based on the results, the oral and dermal LD50 can be considered to exceed 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available results, no classification is warranted for acute toxicity in accorandance to CLP Regulation 1272/2008. The oral and dermal LD50 value was above the limit value of the relevant OECD guideline.