Registration Dossier

Administrative data

Description of key information

- Skin irritation: not irritating in reconstructed human epidermis model (one study acc. to OECD guideline 439 and EU method B.46, GLP). The relative mean tissue viability obtained after 60 minutes treatment with C16-18 DMAPA amidoamine compared to the negative control tissues was 101.8 ± 2.8%. Since the mean relative tissue viability for the test substance was above 50%, C16-18 DMAPA amidoamine is considered to be not irritating.   
- Eye irritation: irreversible effects to the eye in rabbits (one study acc. to OECD guideline 405 and EU method B.5, GLP); undiluted test material applied to right eye of one animal. The eye lesions consisted of an injury of the cornea (opacity maximum grade 2), iridial irritation grade 1 and severe effects on the conjunctivae (grey/white coloration indicating necrosis, redness, chemosis and bloody discharge). Fluorescein examination could not be performed due to the bloody discharge. Scoring of the cornea, iris and eyelids was not possible in vivo 24 hours after instillation due swelling and exudation. Due to the severity of effects in this animal, no further animals were treated. The severity of effects on the eye necessitated intermediate sacrifice of the animal for ethical reasons approximately 27 hours after dosing. Read across from Stearic acid 3-(dimethylaminopropyl)amide

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-10-14 to 2013-11-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, GLP
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
adopted July 26, 2013
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
other: EpiDerm TM (Epi-200 SIT)
Details on test animals and environmental conditions:
not applicable, in vitro test (EpiDerm TM (Epi-200 SIT))
Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Controls:
other: negative control DPBS, positive control 5% SLS solution in deionised water
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg
- wetted with 25 µL DPBS (Dulbecco's Phosphate Buffered Saline)

VEHICLE
no vehicle
Duration of treatment / exposure:
60 min
Observation period:
42 h
Number of animals:
not applicable, in vitro test
Details on study design:
TEST SYSTEM
EpiDerm EPI-200-SIT (MatTek Corporation, 82105 Bratislava, Slovakia); Lot: 18386

APPLICATION
- test substance was applied topically for 60 min to the EpiDerm RHE at 37 ± 1.5 °C, 5 ± 0.5 % C02, 95 ± 5% RH
- after washing: post incubation period of a total of 42 h at 37°C (± 1.5 °C) and 5% CO2 (± 0.5%)
- cell viability was determined by using the standard MTT assay

Negative control: 30 µL DPBS
Positive control: 30µL 5% SDS

REMOVAL OF TEST SUBSTANCE
- after 60 min rinsing with DPBS (15 times)

MTT ASSAY
- at the end of the 42 h post incubation period, tissues were transferred into 24 well plate prepared for the Standard MTT Assay, each well containing 300 µL MTT medium
- the plates were incubated for 3 h at 37°C (± 1°C) and 5 % CO2 (± 0.5 %)
- formazan dye was extracted from the tissues with Isopropanol for 70 h at room temperature
- from each tissue 2 x 200 µL aliquots of the blue formazan solution were transferred into a 96 well microtiter plate; OD was determined at 550 nm

DATA ANALYSIS
- viability in % of the treated tissues was calculated in relation to the corresponding negative control

SCORING SYSTEM:
- cell viability measurement (MTT assay, OD at 550 nm)
- mean tissue vialbility > 50% = non-irritant
- mean tissue viability
Irritation / corrosion parameter:
other: other: tissue viability
Value:
101.8
Remarks on result:
other:
Remarks:
Basis: other: mean of triplicates. Time point: 1 h exposure, 42 h post exposure. Remarks: test substance. (migrated information)
Irritation / corrosion parameter:
other: other: tissue viability
Value:
100
Remarks on result:
other:
Remarks:
Basis: other: mean of triplicates. Time point: 1 h exposure, 42 h post exposure. Remarks: negative control (DPBS). (migrated information)
Irritation / corrosion parameter:
other: other: tissue viability
Value:
3.9
Remarks on result:
other:
Remarks:
Basis: other: mean of triplicates. Time point: 1 h exposure, 42 h post exposure. Remarks: positive control (5% SDS). (migrated information)

No direct MTT reduction capacity of the test substance has been observed.

Viability of epidermal models:

 

 

Negative control

Positive control

5% SDS

Test substance

60 min exposure; 42 h post exposue

100.0 (± 1.9)

3.9 (± 2.7)

101.8 (± 2.8)

result

valid

valid

Not irritant

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
C16-18 DMAPA amidoamine is not irritating in the in vitro skin irritation test under the experimental conditions described in this report.
Executive summary:

In a dermal irritation study according to OECD Guideline 439 (In Vitro Skin Irritation) (26 July 2013) and EU method B.46 (In vitro skin irritation: reconstructed human epidermis model test) (23 July 2009), 25 mg C16-18 DMAPA amidoamine (100% a.i.) was applied in triplicates for 60 min to a three-dimensional human epidermis model (EpiDerm EPI-200-SIT, MatTek Corporation).

After 60 minutes exposure at 37°C, the tissues were rinsed 15 times with phosphate buffered saline to remove residual test substance. Subsequently the skin tissues were incubated for 42 h at 37°C.

Cytotoxicity (irritancy) was expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.

Positive (5% SDS), negative (DPBS (Dulbecco's Phosphate Buffered Saline)) control gave the appropriate response.

The relative mean tissue viability obtained after 60 minutes treatment with C16-18 DMAPA amidoamine compared to the negative control tissues was 101.8 ± 2.8%. Since the mean relative tissue viability for the test substance was above 50%, C16-18 DMAPA amidoamine is considered to be not irritating.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-09-13 to 2012-09-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
May 2008
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 24 April 2002
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 11-13 weeks
- Weight at study initiation: 2.88 kg
- Housing: individually
- Diet (e.g. ad libitum): pelleted rabbit diet, app. 100 g/day, hay + wooden sticks
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24°C
- Humidity (%): 40-70%
- Air changes (per hr):app. 15/h
- Photoperiod (hrs dark / hrs light):12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated contralateral eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 53.6 mg (approximately 0.1 mL)
Duration of treatment / exposure:
eyes were not rindes after treatment
Observation period (in vivo):
24 h
Number of animals or in vitro replicates:
1
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

SCORING SYSTEM: Draine (OECD Guideline 405)
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: ca 27 h
Score:
2
Max. score:
4
Reversibility:
other: no further observation due to severity of effects
Remarks on result:
other: Animal sacrificed and eye scored following the 24 hours observation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: ca 27 h
Score:
0
Max. score:
2
Reversibility:
other: no further observation due to severity of effects
Remarks on result:
other: Animal sacrificed and eye scored following the 24 hours observation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: ca. 27 h
Score:
3
Max. score:
3
Reversibility:
other: no further observation due to severity of effects
Remarks on result:
other: Animal sacrificed and eye scored following the 24 hours observation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24 h
Score:
3
Max. score:
3
Reversibility:
other: no furtehr observation due to severity of effects
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24 h
Score:
4
Max. score:
4
Reversibility:
other: no further observation due to severity of effects
Irritant / corrosive response data:
Instillation of 53.6 mg of the test substance into an eye of one rabbit resulted in severe effects on the eyes, necessitating intermediate sacrifice of the animal for ethical reasons approximately 27 hours after dosing. The eye lesions consisted of an injury of the cornea (opacity maximum grade 2), iridial irritation grade 1 and severe effects on the conjunctivae (grey/white coloration indicating necrosis, redness, chemosis and bloody discharge). Fluorescein examination could not be performed due to the bloody discharge. Scoring of the cornea, iris and eyelids was not possible in vivo 24 hours after instillation due swelling and exudation. Due to the severity of effects in this animal, no further animals were treated.
Other effects:
No remnants were noted one and 24 hours after instillation. White remnants of the test substance were found ex vivo in the conjunctival sac of the eye following sacrifice, 27 hours after instillation.
No symptoms of systemic toxicity were observed in the animal during the test period.

 

1 h

24 h

Ex vivo (Animal sacrificed and eye scored following the 24 hours observation)

Cornea, opacity

0

n.a.

2

Iris

1

n.a.

0

Conjunctival redness

2

3

3

Chemosis

4

4

n.a.

Conjunctival discharge

2

3

n.a.

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
In this study, Stearic acid 3-(dimethylaminopropyl)amide has irreversible effects on the eyes (Category 1).
Executive summary:

In a primary eye irritation study according to OECD guideline 405, adopted 24 April 2002 and EU method B.5, May 2008, 53.6 mg (approximately 0.1 mL) of Stearic acid 3-(dimethylaminopropyl)amide was instilled into the conjunctival sac of an eye of a male young adult New Zealand White rabbit. The eye was not rinsed after application. The animal was observed for 24 h.  Irritation was scored by the method of Draize.

Instillation of the test substance into the eye resulted in severe effects on the eyes, necessitating intermediate sacrifice of the animal for ethical reasons approximately 27 hours after dosing.

The eye lesions consisted of an injury of the cornea (opacity maximum grade 2), iridial irritation grade 1 and severe effects on the conjunctivae (grey/white coloration indicating necrosis, redness, chemosis and bloody discharge).

Fluorescein examination could not be performed due to the bloody discharge. Scoring of the cornea, iris and eyelids was not possible in vivo 24 hours after instillation due to swelling and exudation. Due to the severity of effects in this animal, no further animals were treated.

In this study, Stearic acid 3-(dimethylaminopropyl)amide has irreversible effects on the eyes (Category 1).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In vitro skin irritation data are available for the target substance C16-18 DMAPA amidoamine and for the source substance Stearic acid 3-(dimethylaminopropyl)amide. In vivo tests for skin and eye irritation are available with the structurally closely related source substance Stearic acid 3-(dimethylaminopropyl)amide. A justification for read-across is given below.

 

Skin irritation

In an in vitro dermal irritation study according to OECD Guideline 439 (In Vitro Skin Irritation) (26 July 2013) and EU method B.46 (In vitro skin irritation: reconstructed human epidermis model test) (23 July 2009), 25 mg C16-18 DMAPA amidoamine (100% a.i.) was applied in triplicates for 60 min to a three-dimensional human epidermis model (EpiDerm EPI-200-SIT, MatTek Corporation).

After 60 minutes exposure at 37°C, the tissues were rinsed 15 times with phosphate buffered saline to remove residual test substance. Subsequently the skin tissues were incubated for 42 h at 37°C.

Cytotoxicity (irritancy) was expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment. Positive (5% SDS), negative (DPBS (Dulbecco's Phosphate Buffered Saline)) control gave the appropriate response.

The relative mean tissue viability obtained after 60 minutes treatment with C16-18 DMAPA amidoamine compared to the negative control tissues was 101.8 ± 2.8%. Since the mean relative tissue viability for the test substance was above 50%,C16-18 DMAPA amidoamine is considered to be not irritating.

 

In an in vitro dermal irritation study according to OECD guideline 439, adopted 22 July 2010 and EU method B.46, August 2009, Stearic acid 3-(dimethylaminopropyl)amide was applied in triplicate to EPISKIN tissues for 15 min. PBS was used as negative control, 5% SDS as positive control. After exposure the skin tissues were thoroughly rinsed to remove the test substance and transferred to fresh medium. After a 42 hour post-incubation period, determination of the cytotoxic (irritancy) effect was performed.

The relative mean tissue viability obtained after 15 minutes treatment with the test substance compared to the negative control tissues was 108%. Since the mean relative tissue viability was above 50%, the test substance is considered to be non-irritant.

The positive control had a mean cell viability of 5% after 15 minutes exposure. The absolute mean OD570 (optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was less than 6%, indicating that the test system functioned properly.

In this in vitro skin irritation test, Stearic acid 3-(dimethylaminopropyl)amide was not irritating.

Although the in vitro test alone would have been sufficient for classification, labelling and risk assessment and is considered to be scientifically valid for the prediction of irritant and non-irritant chemicals for Annex VII, and also Annex VIII, a confirmatoryin vivotest has been performed.

This was due to the unexpectedly severe outcome of the in vivo eye irritation test: although the preceding in vitro BCOP assay showed no evidence of the test substance being corrosive,Stearic acid 3-(dimethylaminopropyl)amide produced irreversible effects to the eye in vivo (for details, see below). This result has created some doubt concerning the reliability of the in vitro skin irritation test for the test substance. Thus, to take no risk for human health, a subsequent in vivo skin irritation test has been conducted.

 

In a primary dermal irritation study according to OECD Guideline 404, adopted 24 April 2002, and EU Method B.4, May 2008, 3 young adult New Zealand white rabbit of one sex were dermally exposed to 0.5 g of Stearic acid 3-(dimethylaminopropyl)amide (100% a.i) to 6 cm² skin surface. The first animal was subsequently exposed for 3 minutes, 1 and 4 hours. Two further animals were exposed for 4 hours. Animals then were observed for 7 (animal #1) or 14 days (animals #2, #3). 

In animal 1, no signs of skin reactions were recorded after removing the patch applied for 3 minutes and 1 hour in the observations carried out after removing the patches. After the 4 hours exposure to the test item, very slight oedema (grade 1) was observed one hour after removing the patch. Skin reactions observed in this animal during the observations made 24 and 48 hours after removing the patch were slight erythema (grade 2) and very slight edema (grade 1). After 72 hours, there was very slight erythema and very slight edema (grade 1) that was fully reversible within 7 days.

In animals 2 and 3, very slight edema (grade 1) and very slight erythema (grade 1) were observed 1 h after patch removal. At the 24, 48 and 72 h observations slight erythema (grade 2) and very slight or slight edema (grade 1 - 2) were noted. Scaliness was seen in these two animals after 7 days. The skin irritation resolved within 15 days. The means of the erythema and edema evaluations at 24, 48 and 72 hours for the three animals after a four-hour exposure were 1.6, 2 and 2 (erythema) and 1, 1.3 and 1 (edema). In this study, Stearic acid 3-(dimethylaminopropyl)amide is classified as not irritating to rabbit skinaccording the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).

 

Eye irritation

An in vitro study was performed initially to assess the corneal irritation and damage potential ofStearic acid 3-(dimethylaminopropyl)amideby means of the BCOP assay using fresh bovine corneas according to OECD guideline 437, adopted 7 September 2009 and EU method B.47, December 2010.

Since no workable suspension of the test substance in physiological saline could be obtained, the test substance was used as delivered by the sponsor and added pure on top of the corneas (308 to 311 mg test substance). Physiological saline was used as negative control, 20% (w/v) Imidazole in physiological saline as positive control.

The corneas were incubated with Stearic acid 3 -(dimethylaminopropyl)amide for 240±10 min at 32±1°C. The test was performed in triplicates. After rinsing the corneas at least 3 times, opacity and permeability were determined. The in vitro irritancy score (IVIS) were calculated as mean opacity value + (15 x mean OD490 value); a substance that induces an IVIS ≥ 55.1 is defined as a corrosive or severe irritant. The positive and negative controls induced the appropriate responses.

The corneas treated with Stearic acid 3 -(dimethylaminopropyl)amide showed opacity values ranging from 1 to 4 and permeability values ranging from 0.990 to 2.790. The corneas were covered with small spots after the 240 minutes of treatment. The in vitro irritancy scores ranged from 16 to 44. The mean in vitro irritancy score was 29 after 240 minutes of treatment with Stearic acid 3-(dimethylaminopropyl)amide.

 

Because the testing result (meanin vitroirritancy score of 29) was well below an IVIS of 55.1, additional testing had to be conducted for classification and labelling purposes in accordance with the accepted integrated testing strategy (ITS) for assessing the eye irritation potential of substances (REACH TGD R7a).

In a primary eye irritation study according to OECD guideline 405, adopted 24 April 2002 and EU method B.5, May 2008, 53.6 mg (approximately 0.1 mL) of Stearic acid 3-(dimethylaminopropyl)amide was instilled into the conjunctival sac of an eye of a male young adult New Zealand White rabbit. The eye was not rinsed after application. The animal was observed for 24 h.  Irritation was scored by the method of Draize.

Instillation of the test substance into the eye resulted in severe effects on the eyes, necessitating intermediate sacrifice of the animal for ethical reasons approximately 27 hours after dosing.

The eye lesions consisted of an injury of the cornea (opacity maximum grade 2), iridial irritation grade 1 and severe effects on the conjunctivae (grey/white coloration indicating necrosis, redness, chemosis and bloody discharge).

Fluorescein examination could not be performed due to the bloody discharge. Scoring of the cornea, iris and eyelids was not possible in vivo 24 hours after instillation due to swelling and exudation. Due to the severity of effects in this animal, no further animals were treated.

In this study, Stearic acid 3-(dimethylaminopropyl)amide has irreversible effects on the eyes (Category 1) according the criteria of CLP, EU GHS (Regulation (EC) No 1272/2008).

 

Respiratory irritation

No data on the respiratory irritation of C16-18 DMAPA amidoamine are available.

 

There are no data gaps for the endpoint irritation/corrosion. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans.

 

Justification for read-across

1. Read-across hypothesis and justification

This read-across is based on the hypothesis that source and target substances have similar toxicological properties because

·        they are manufactured from similar resp. identical precursors under similar conditions

·        the metabolism pathway leads to comparable products (amine backbone and long chain fatty acids) and non-common products predicted to have no toxicological effects (long chain fatty acids).

 

Therefore, read-across from the existing irritation studies on the source substance is considered as an appropriate adaptation to the standard information requirements of Annex VII, 8.1, 8.2, Annex VIII, 8.1.1, and 8.2.1 of the REACH Regulation for the target substance, in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

The justification of the proposed read-across approach is elaborated in the next chapters.

 

2. Justification for read-across

2.1 Substance Identity

Table 1: Substance identities

 

Source substance

Target substance

Stearic acid 3-(dimethylaminopropyl)amide

C16-18 DMAPA amidoamine

mono constituent substance

UVCBsubstance

CAS number

7651-02-7

Chain length distribution

< C16: < 1.6%

C16: < 7%

C18: > 89.8%

> C18: < 1.6%

C14: <= 5 %

C16: 25-35 %

C18: >= 61 %

DMAPA

<0.002%

<=0.01%

 

2.1 Substance Identity

Substance descriptions

The target substance C16-18 DMAPA amidoamine is a UVCB substance manufactured from saturated C16-18 fatty acids and N, N-dimethylpropylenediamine (DMAPA). It is composed of C16 and C18 amides of DMAPA, with C18 being the larger part (>/= 61%)

 

The source substance Stearic acid 3-(dimethylaminopropyl)amide is manufactured from octadecanoic acid andN, N-dimethylpropylenediamine. It is composed of mainly C18 amides (> 89.8%) of DMAPA and small amounts of the C16 amide (<7%).

 

2.2 Common breakdown products

The source substance Stearic acid 3-(dimethylaminopropyl)amide is the main component of the UVCB target substanceC16-18 DMAPA amidoamine. The only difference is the chain length distribution: the target substance also contains a significant amount of the C16 amide.

This is not considered to be of relevance for metabolism.Both substances are amides which after resorption may be hydrolysed by amidases resulting in free fatty acids and DMAPA. The carboxylic acids then are further degraded by the mitochondrial beta-oxidation process (for details see common text books on biochemistry). The fatty acids enter normal metabolic pathways and are therefore indistinguishable from fatty acids from other sources including diet. The amine compounds are not expected to be further metabolised, but excreted via the urine mainly unchanged. 

 

2.3 Differences

The slight differences in fatty acid chain length (higher percentage of C16 in the target substance vs. corresponding higher percentage C18 in the source substance) are not considered to be of major relevance for local effects.

 

3. Physicochemical properties:

Table 2: Physicochemical properties

 

Endpoints

Source substanceStearic acid 3-(dimethylaminopropyl)amide

Target substanceC16-18 DMAPA amidoamine

Molecular weight

368.64 g/mol

340.59 - 368.64

Physical state at 20°C / 1013 hPa

Solid (paste)

Solid (waxy)

Melting point

OECD TG 102, RL1, non-GLP

67.4°C

OECD TG 102, RL1, non-GLP

41.8°C

Boiling point

OECD TG 103, RL1, non-GLP

412.3°C

OECD TG 103, RL1, non-GLP

320.5°C

Surface tension

ISO 4311, plate method, RL1, non-GLP

37.86 mN/m at 0.22 g/L

OECD TG 115, ring method, RL1, non-GLP

26.7 mN/m at 2.7 mg/L

Water solubility

OECD TG 105, RL1, non-GLP

10 mg/L at 20°C

OECD guideline 105/EU method A.6, slow stirring method/HPLC, RL1, non-GLP

3.65 mg/L at 23°C

Log Kow

---

Calculation (ACD/Labs Release 12.00, Product version 12.01 )

>6.6

EU method A.8, calculation based on solubility in n-Octanol and water; RL2, non-GLP

2.01 at 20°C, pH7

Read-across from Stearic acid 3-(dimethylaminopropyl)amide

Vapour pressure

OECD TG 104, RL1, ISO17025 compliance

3.4E-08 Pa at 20°C

Read-across from Stearic acid 3-(dimethylaminopropyl)amide

 

 

4. Comparison of data from human health endpoints

4.1 Toxicity data of the target and source substances

Table 3: General toxicological profiles forStearic acid 3-(dimethylaminopropyl)amide andC16-18 DMAPA amidoamine

Endpoints

Source substance

Stearic acid 3-(dimethylaminopropyl)amide

Target substanceC16-18 DMAPA amidoamine

Acute toxicity oral

OECD TG 423, RL1,GLP

 

LD50(rat) > 2000 mg/kg bw

OECD TG 423, RL1,GLP

 

LD50(rat) > 2000 mg/kg bw

Eye irritation

OECD TG 405, RL1, GLP

 

Category 1 (irreversible effects on the eye)

No data; read-across

OECD TG 437, RL1, GLP

 

not severely irritating /not corrosive

No data; read-across

Skin irritation

OECD TG 439, RL1, GLP

 

not irritating

OECD TG 439, RL1, GLP

 

not irritating

OECD TG 404, RL1, GLP

 

not irritating

No data; read-across

Sensitisation

 

OECD TG 406 (GPMT), RL1, GLP

 

not sensitising

No data; read-across

Genotoxicity

OECD TG 471 (Ames test), RL1, GLP

 

Negative

OECD TG 471, RL1, GLP

 

Negative

OECD TG 467 (MLY), RL1, GLP

 

Negative

No data; read-across

OECD TG 473 (Chromosome aberrations), RL1, GLP

 

Negative

No data; read-across

Repeated dose toxicity oral

Similar to OECD TG 407 (14 d DRF), rat, RL1, GLP

 

clinical signs/mortality (all animals at 500 mg/kg bw/d were sacrificed for humane reasons); haematology (slightly lower red blood cell and higher reticulocyte counts in males at 50 and 200 mg/kg bw/d); clinical biochemistry (higher ALAT activity in 2 males at 50 mg/kg bw/d, 2 males and 1 female at 200 mg/kg bw/d, higher alkaline phosphatase activity in 1 female at 200 mg/kg bw/d, higher potassium level in males at 50 and 200 mg/kg bw/d)

No data; read-across

Repeated dose toxicity dermal

Similar to OECD TG 411, rabbit, RL2, GLP

 

NOAEL(systemic) = 200 mg/kg bw/d (highest dose administred)

No data; read-across

Reproduction / Developmental Toxicity Screening Test

OECD TG 421, rat, RL1, GLP

 

NOAEL(parental)= 70 mg/kg bw/d;

NOAEL(fertility females)= 70 mg/kg bw/d;

NOAEL (fertility males) = 200 mg/kg bw/d;

NOAEL(development)= 200 mg/kg bw/d

No data; read-across

Prenatal developmental toxicity

Similar to OECD TG 414, rabbit, RL2, GLP

 

NOAEL(development)=200 mg/kg bw/d (highest dose administered)

No data; read-across

 

Experimental data for the target substance C16-18 DMAPA amidoamine are available for acute oral toxicity, skin irritation (in vitro) and genotoxicity (bacterial reverse mutation assay).

No experimental data are available for the target substance C16-18 DMAPA amidoamine concerning the endpoints eye irritation, sensitisation, repeated dose toxicity, and reproductive/developmental toxicity. However, as demonstrated above, the source substance Stearic acid 3-(dimethylaminopropyl)amide isthe main constituent of the target substance. The additional minor constituents with differing fatty acid chain lengths are not considered to influence the outcome of the toxicological studies.

This is supported by the similar results observed in acute oral toxicity studies: Both, the target substance C16-18 DMAPA amidoamine and the source substance Stearic acid 3-(dimethylaminopropyl)amide are of low acute toxicity when administered orally. The LD50 for both substances was > 2000 mg/kg bw. In both studies, 2/6 animals died during the observation period.

Both, the target substance C16-18 DMAPA amidoamine and the source substance Stearic acid 3-(dimethylaminopropyl)amide were not irritating to skin in an in vitro skin irritation test.

Both, the target substance C16-18 DMAPA amidoamine and the source substance Stearic acid 3-(dimethylaminopropyl)amide were not mutagenic in the bacterial reverse mutation assay when tested up to cytotoxic concentrations.

 

4.2 Quality of the experimental data of the analogues:

Skin irritation:

The target substance has been tested in a GLP compliant OECD Guideline 439 study.

The source substance has been tested in GLP compliant OECD Guideline 404 and OECD Guideline 439 studies (both RL1). There are no uncertainties, thus the studies can be used in an analogue approach. The available data are sufficiently reliable and can be used in an analogue approach.

 

Eye irritation:

The source substance has been tested in GLP compliant OECD Guideline 405 and OECD Guideline 437 studies (both RL1). There are no uncertainties, thus the studies can be used in an analogue approach. The available data are sufficiently reliable and can be used in an analogue approach.

4.4 Classification and labelling

Concerning human health hazards, the source substance Stearic acid 3-(dimethylaminopropyl)amide is classified for irreversible effects on the eye (Eye Damage, Category 1, H318: Causes serious eye damage. / Xi; R41 Risk of serious damage to eyes). Based on the read-across, the target substance C16-18 DMAPA amidoamine will be classified accordingly.

 

5. Conclusion

The structural similarities between the source and the target substances and the similarities in their breakdown products presented above support the read-across hypothesis. Adequate and reliable scientific information indicates that the source and target substances and their subsequent degradation products have similar toxicity profiles.

The skin irritation potential of target substance C16-18 DMAPA amidoamine as well as of the source substance Stearic acid 3-(dimethylaminopropyl)amide were low. The target substance C16-18 DMAPA amidoamine contains a small amount of additional Palmitic acid 3-(dimethylaminopropyl)amide (C16), which was shown to have no influence on skin irritation properties.

By classifying the target substance C16-18 DMAPA amidoamine for irreversible effects on the eyes (Category 1) according to the results with the read-across substance a sufficient degree of conservatism is applied.

 

 


Justification for selection of skin irritation / corrosion endpoint:
OECD & EC guideline study, no deviations, GLP

Justification for selection of eye irritation endpoint:
OECD & EC guideline study, no deviations, GLP

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation

Based onreliable, adequate and relevant data, C16-18 DMAPA amidoamine does not need to be classified for skin irritation according to regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC.

 

Eye irritation

Based onreliable, adequate and relevant data obtained with the source substance Stearic acid 3-(dimethylaminopropyl)amide, the target substance C16-18 DMAPA amidoamine has to be classified in Category 1, irreversible effects on the eye according to CLP, EU GHS (Regulation (EC) No 1272/2008) and is assigned the hazard statement H318 and the signal word “Danger”. According to the criteria set out in directive 67/548/EEC C16-18 DMAPA amidoamineis classified as “Risk of serious damage to eyes” and is therefore assigned the risk phrase R41.