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

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted, 24 February 1987

Deviations:

no

Test guideline 2

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

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:

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

Administration / exposure

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.

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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

   

Applicant's summary and conclusion

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.