Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates

Endpoint summary

Description of key information

The most recent and reliable study results to classification in Category 4 for acute oral toxicity (LD50 between 300 and 2000 mg/kg bw) in accordance with Regulation (EC) No 1272/2008. Acute dermal toxicity LD50 is > 2000 mg/kg bw on the basis of read-across with existing data on diamines compounds. There is no data available on acute toxicity via inhalation.

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:

26 April 2012 - 21 June 2012

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: 210 g (range: 202 g to 219 g)
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 6 days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: 16 May 2012 to 14 June 2012.

Route of administration:

oral: gavage

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Justification for choice of vehicle:
The vehicle used in this study was selected from the results of solubility assays performed by the CiToxLAB France Pharmacy.
In the absence of recommendation from the Sponsor, the solubility assay first started at the concentration of 200 mg/mL, and the first choice vehicle was drinking water treated by reverse osmosis using an Elix 5 plus apparatus (Millipore SA, Saint-Quentin-en-Yvelines, France).
After 10 minutes under magnetic stirring, a yellow solution was obtained at the concentration of 200 mg/mL in this vehicle.
- Maximum dose-volume applied: 20 mL/kg

DOSAGE PREPARATION (if unusual):
The test item was administered as a solution in the vehicle. The test item was mixed with the required quantity of vehicle and then homogenized using a magnetic stirrer.
Only glass was used during preparation.
Dose formulations preparations were prepared by the CiToxLAB France Pharmacy extemporaneously on the day of each administration.
The dose formulations were stored at room temperature and delivered to the study room in brown glass flasks.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose:
Since some discrepancies were observed when the estimation of a lethal dose-level had been performed with the test item with solvent, it was decided to administer the test item without solvent at the starting dose level of 300 mg/kg for animal welfare reasons.
After treatment at the starting dose-level, the next dose-levels were administered in a sequential manner, under the same conditions to different animals, based to the flow charts of OECD Guideline No. 423, 17th December 2001, which are equivalent to those of Commission Regulation (EC) No. 440/2008, B.1tris (30 May 2008). The selected dose-levels corresponded to the current limit values of classification of chemical substances. As no mortality was observed after treatment of the first group at the dose-level of 300 mg/kg, the second group was treated at the dose-level of 2000 mg/kg.
As mortality was observed after treatment of the second group at the dose-level of 2000 mg/kg, the third group was treated at the dose-level of 300 mg/kg.

Doses:

300 and 2000 mg/kg.

No. of animals per sex per dose:

3 females per treatment step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, 1/3 females was found dead on day 2. Prior to death, piloerection was observed on day 1 (0h30 minutes after treatment).
One other female from this group was prematurely sacrificed on day 7. Prior to sacrifice, piloerection, thin appearance, soiled urogenital region, hypothermia (cold to the touch) and hypoactivity were observed.

Clinical signs:

other: At 300 mg/kg (first assay), all animals presented piloerection during the first 4 hours after treatment. At 2000 mg/kg, piloerection, soiled urogenital region, thin appearance, hypoactivity and hunched posture were recorded in the surviving female. At 30

Gross pathology:

No gross findings were attributed to treatment with the test item.

see Executive summary

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 of the test item was comprised between 300 and 2000 mg/kg in rats.
According to the criteria of Regulation (EC) No 1272/2008, the test item should be classified category 4 and assigned the signal word "warning" and the hazard statement "H302: Harmful if swallowed".

Executive summary:

The objective of this study was to evaluate the potential acute toxicity of the test item following a single oral administration (gavage) to rats.

 

Methods

The test item was administered once by oral route (gavage) to three groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test item was prepared in drinking water treated by reverse osmosis.

Since some discrepancies were observed when the estimation of a lethal dose-level had been performed with the test item with solvent, it was decided to administer the test item without solvent at the starting dose-level of 300 mg/kg for animal welfare reasons.

After the first assay, the next higher dose-level of 2000 mg/kg was tested. Then, as mortality was observed after treatment of the second group at the dose-level of 2000 mg/kg, the third group was treated at the dose-level of 300 mg/kg.

Each animal was observed once a day for mortality and clinical signs for 15 days. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination.Macroscopic lesions were preserved in buffered formalin, then destroyed at the finalization of the study report as no microscopic examination was performed.

 

Results

At 2000 mg/kg, 1/3 females was found dead on day 2. Piloerection was observed prior to death. Piloerection, soiled urogenital region, thin appearance, hypoactivity and hunched posture were recorded in the surviving female.

One other female from this group was prematurely sacrificed on day 7. Prior to sacrifice, piloerection, thin appearance, soiled urogenital region, hypothermia (cold to the touch) and hypoactivity were observed.

At 300 mg/kg (first assay), all animals presented piloerection during the first four hours after treatment.

At 300 mg/kg (confirmatory assay), piloerection was noted in all females. Hypoactivity, hunched posture, loud and abdominal breathing, half-closed eyes, thin appearance, increase in size of abdomen and pallor of extremities were recorded in 1/3 females.

When compared to CiToxLAB historical control data, a lower body weight gain was noted at 300 mg/kg (first assay) in two female between day 1 and day 15.

A body weight loss and lower body weight gain was noted at 2000 mg/kg in the surviving female between day 1 and day 8 and between day 8 and day 15, respectively.

At 300 mg/kg (confirmatory assay), a body weight loss and lower body weight gain were noted in 1/3 females between day 1 and day 8 and between day 8 and day 15, respectively. A lower body weight gain was also noted in another female of this group between day 1 and day 8.

No gross findings were attributed to treatment with the test item.

 

Conclusion

The oral LD₅₀ of the test item was comprised between 300 and 2000 mg/kg in rats.

According to the criteria of Regulation (EC) No 1272/2008, the test item should be classified category 4 and assigned the signal word "warning" and the hazard statement "H302: Harmful if swallowed".

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

No substance identification; only "EC 63". No QA / GLP. Deviations from the current OECD402 guideline; 2 animals were used per sex per dose group in stead of 5. Half of the animals had abraded skin.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

: Only 2 animals per sex per dose group were used, 4 animals in total, in stead of 5. Half of the animals had abraded skin.

Principles of method if other than guideline:

See deviations

GLP compliance:

no

Test type:

standard acute method

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 2.13-3.00 Kg
- Fasting period before study: no data
- Housing: animals were caged individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 18
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: No data

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: trunk of the animals
- % coverage: 10
- Type of wrap if used: The treated area was covered with a thin layer of cellulose sheet and wrapped in polyethylene foil .

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance was removed from the skin with water and the animals were wiped dry with towels.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.0 (control), 0.7, 1.4 and 2.0 g/kg body weight.
- Concentration (if solution): no data
- Constant volume or concentration used: yes; 9 ml/kg body

VEHICLE
- Amount(s) applied (volume or weight with unit): 9 ml/kg body
- Concentration (if solution): no data
- Lot/batch no. (if required): no data
- Purity: no data

Duration of exposure:

24h

Doses:

0.0 (control), 0.7, 1.4 and 2.0 g/kg body weight.

No. of animals per sex per dose:

2

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations and weighing at the start of the study and after week 1 and 2
- Necropsy of survivors performed: yes
- Other examinations performed: examinations were carried out for possible changes in blood composition and for macroscopic appear of severak organs, water and food consumption were measured.

Key result

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occured.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

Gross examination at autopsy did not reveal any treatment-related changes.

Other findings:

Haematological data were comparable for all groups.

Interpretation of results:

GHS criteria not met

Conclusions:

From the present results it is concluded that the product EC 63 is practically non-toxic in the case of one single dermal application. LD50 > 2000 mg/kg bw

Executive summary:

There is no substance identification; only "EC 63".

No QA / GLP.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

Animals were exposed to the test substance was under occlusion and the area of expsoure was 30%. Necropsy is only performed on that died during the observation period. The substance is corrosive to skin and eyes but in this part of the study nothing is mentioned about skin damage.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

The test aniamls were exposed under occlusion and the test ietm covered 30% of the body surface.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: H . A . R . E . - Rabbits for Research, Hewitt, N.J., US (H.A.R.E. - Rabbits i s a USDA approved supplier. )
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: not applicable
- Housing: individually in wire mesh bottom cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum if 5 days

ENVIRONMENTAL CONDITIONS
no data

IN-LIFE DATES:
no data

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: 30
- Type of wrap if used: The occlusive binder consisted of a layer of plastic wrap, a protective cloth and stockinette binder, all securely held in place with masking tape. The occlusive binder is applied to maintain contact and minimize evaporation of the applied test article .

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The exposure sites were then gently wiped with clean gauze to remove as much nonabsorbed test article as possible.
- Time after start of exposure: After an exposure period of 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2g/kg
- Concentration (if solution): -
- Constant volume or concentration used: yes

Duration of exposure:

24h

Doses:

2g/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded on the initial day of testing and at study termination or day of death.
- Necropsy of survivors performed: no

Statistics:

E . L . Crow, Biometrika, 43, 423-435 (1956)

Preliminary study:

not peformed

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal died during the 14 day observation period on day 13

Clinical signs:

other: not reported

Gross pathology:

not reported

Other findings:

not reported

Interpretation of results:

GHS criteria not met

Conclusions:

One animal died on day 13. The LD50 for duomeen C is therefore > 2000 mg/kg bw

Executive summary:

The acute dermal toxicity Duomeen C was tested in New Zealand White Rabbits according to a study design similar to OECD 402. The back and flanks of 5 male and 5 female rabbits were clipped, constituting about 30% of the total body surface. Just prior of the application test substance, the skin surface was abraded in 3 of the males and 2 of the females. The animals received 2000 mg/kg undiluted test material, which was left under occlusion for 24 hours. After the 24 hours exposures, the sites were gently wiped with clean gauze to remove non-absorbed material. One animal died during the 15-day observation period on day 13. Consequently, LD50 was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The most recent and reliable study results to classification in Category 4 for acute oral toxicity (LD50 between 300 and 2000 mg/kg bw) in accordance with Regulation (EC) No 1272/2008. Acute dermal toxicity LD50 is > 2000 mg/kg bw on the basis of read-across with existing data on diamines compounds. There is no data available on acute toxicity via inhalation.

 

Oral

There are four studies available for evaluation of Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates. Three studies (CIT 1997, 2003 and 2005) were performed on mixture containing the substance around 28 to 38%, as well as 25 to 33% of 2-butoxyethanol (CAS 111-76-2) and approximately 37% of water (complement to 100%). Although it is assumed that the solvent has minor impact on the acute oral toxicity of the substance, some unclear differences in the results of these three studies conducted to the performance of a new study without solvent and with a purity of the test item of 96.7%.

 

In the selected key study (CIT, 38931 TAR, 2008), the toxic effects following an acute oral dose of of Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates was determined according to the guideline for the acute toxic class method (OECD 423) performed under GLP.

At 2000 mg/kg bw, 1/3 females was found dead on day 2. Piloerection was observed prior to death. One other female from this group was prematurely sacrificed on day 7. Prior to sacrifice, piloerection, thin appearance, soiled urogenital region, hypothermia (cold to the touch) and hypoactivity were observed. Piloerection, soiled urogenital region, thin appearance, hypoactivity and hunched posture were recorded in the surviving female. A body weight loss (from day 1 to 8) following by a lower body weight gain (from day 8 to 15) was also noted in this female.

At 300 mg/kg bw (first assay), all animals presented piloerection during the first four hours after treatment. Compared to historical control data, a lower body weight gain was noted) in two female between day 1 and day 15. At the confirmatory assay (300 mg/kg), piloerection was noted in all females. Hypoactivity, hunched posture, loud and abdominal breathing, half-closed eyes, thin appearance, increase in size of abdomen and pallor of extremities were recorded in 1/3 females. A body weight loss and/or lower body weight gain were noted in 2/3 females.

No gross findings were attributed to treatment with the test item.

 

 

The next GLP study (CIT, 29235 TAR, 2005) evaluated the toxicity of Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates according to OECD 423.The assay was performed on a mixture containing 28-34%, Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates, 28-33% 2-butoxyethanol and water (complement to 100%). The study was performed according to OECD guideline and under GLP method

The test substance was administered in purified water via oral gavage to female Sprague Dawley rats at dose ranges of 50, 300 and 2000mg/kg bw in a dosage volume of 10mL/kg bw. One group of 3 females was tested at 2000 mg/kg bw while at 300 and 50 mg/kg bw, 2 groups of 3 females each were tested. No mortality was observed at 50 mg/kg bw. Two out of six females were found dead on day 13 or 15 at 300 mg/kg bw and all the animals were found dead on day 2 or 3 at 2000 mg/kg bw. No clinical signs were observed at 50 mg/kg bw. In almost all surviving animals given 300 mg/kg bw, hypoactivity, piloerection, dyspnea, hypersalivation and/or swollen abdomen were noted between days 1 and 22. Sedation, piloerection, dyspnea, hypersalivation and sometimes coma were observed prior death in animals receiving 2000 mg/kg bw.

Compared to historical control data, a body weight loss or reduced body weight gain was observed among the 300 mg/kg bw dose group while a reduced body weight gain was noted in few females given 50 mg/kg bw.No apparent abnormalities were observed in any animal at necropsy.

 

 

Another GLP study (CIT 26129 TAR, 2003), evaluated the toxicity of Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates according to OECD 423.The assay was performed on a mixture containing 30-40%, Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates, 25-35% 2-butoxyethanol and water (complement to 100%). The study was performed according to OECD guideline and under GLP method

The test substance was administered in purified water via oral gavage to Sprague Dawley rats at dose ranges of 25, 200 and 2000 mg/kg bw in a dosage volume of 10mL/kg bw. Two groups of 3 males were tested at 200 or 2000 mg/kg bw while two groups of 3 females were tested at 200 and 25 mg/kg bw. No clinical signs and no mortality occurred in the females treated at 25 mg/kg bw. At the 200 mg/kg bw dose-level, no clinical signs and no mortality were recorded in males. In females, 2/3 animals were found dead on day 11 or 14; hypoactivity or sedation, piloerection, dyspnea and swollen abdomen, together with lateral recumbency in one of them, were noted prior to death. In the surviving female, hypoactivity or sedation was observed on day 1, piloerection and dyspnea on day 2, and hypoactivity, piloerection and swollen abdomen on days 6 and 7; then dyspnea, piloerection, swollen abdomen and loud breathing were noted between day 8 and the end of the observation period (day 15). At the 2000 mg/kg bw dose-level, 2/3 males were found dead on day 2 or 4; hypoactivity, piloerection and dyspnea, together with soft feces in one of them, were noted prior to death. In the surviving male, hypoactivity and piloerection, together with dyspnea between days 1 and 3 and soft feces between days 2 and 4, were observed from day 1 up to day 4.Slight to moderate reduced body weight gain was observed at all dose-levels when compared to historical control data.At necropsy, the stomach and intestines of the female No. 09 given 200 mg/kg bw were distended with air. No apparent abnormalities were observed in the other animals. Under the experimental conditions of this study, the oral LD₅₀of the test item, Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates, iscomprised between 200 and 2000 mg/kg bw in male rats and between 25 and 200 mg/kg bw in female rats.

 

 

Another GLP study (CIT 15491 TAR, 1997), evaluated the toxicity of Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates according to OECD 401. The assay was performed on a mixture containing 38%, Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates, 25% 2-butoxyethanol and 37% water. The study was performed according to OECD guideline and under GLP method although no formal analytical certificate was available as the product was in phase of development at that time. The test substance was administered by oral route (gavage) to groups of five male (at 2000 mg/kg bw) and/or five female (at 2000, 1735 and 1500 mg/kg bw) Sprague-Dawley rats in purified water and administered to the animals under a volume of 10 ml/kg bw. At the 1500 mg/kg bw dose-level, hypoactivity and piloerection were noted in all animals on days 1 and 2. Recovery was complete on day 3 in all animals. At the 1735 mg/kg bw dose-level, hypoactivity or sedation and piloerection were noted in all animals on day 1. Three animals were found dead on day 2. One of the remaining animals was found dead on day 5 and the last one was found dead on day 7. Sedation, piloerection, dyspnoea, psosis, tremors and lateral recumbency were noted in these animals prior.

At the 2000 mg/kg bw dose-level, hypoactivity or sedation, piloerection and dyspnoea were observed on day 1 in almost all animals. These clinical signs persisted up to day 9 at the latest. Stiff gait was also noted in one animal on day 9. One male died on day 1, 5 hours after dosing, two males and one female were found dead on day 2, three females were found dead on day 10

The body weight of the surviving animals given 1500 or 2000 mg/kg bw was reduced when compared to that of historical control animals.

 

Dermal

Available data exist for N-C16-18-alkyl-(evennumbered, C18 unsaturated) propane-1,3-diamine and N-Coco-1,3-diaminopropane (N-C12-18-alkyltrimethylenediamines) . Although the information related to the test materials are poorly reported (especially for the C16-18, C18- unsaturated diamine), a weight of evidence approach could be applied to consider the dermal LD50 of Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, diacetates higher than 2000 mg/kg bw. Indeed despite a dermal absorption expected increased due to the corrosive properties of the diamine compounds, an LD50 > 2000 mg/kg bw was observed for both diamines.

 

The acute dermal toxicity of N-C16-18-alkyl-(evennumbered, C18 unsaturated) propane-1,3-diamine (only identified EC63) was tested in New Zealand White Rabbits according to a study design similar to OECD 402. The back and flanks of 2 male and 2 female rabbits were clipped, constituting about 10% of the total body surface. The animals received 0, 0.7, 1.4 and 2 g/kg bw of the material in vehicle (propylene glycol) at 9 mL/ kg bw. which was left under occlusion for 24 hours. After the 24 hours exposures, the sites were gently wiped with water and dry towels to remove non-absorbed material. No mortality occurred during the 15-day observation period. Consequently, LD50 was determined to be > 2000 mg/kg bw. No clinical or macroscopic findings were observed. Hematological data were comparable for all groupes.

 

The acute dermal toxicity of N-Coco-1,3-diaminopropane (N-C12-18-alkyltrimethylenediamines) was tested in New Zealand White Rabbits according to a study design similar to OECD 402 (F&D Res.Lab, SD-1684, 1981 - pre-GLP). The back and flanks of 5 male and 5 female rabbits were clipped, constituting about 30% of the total body surface. Just prior of the application test substance, the skin surface was abraded in 3 of the males and 2 of the females. The animals received 2000 mg/kg undiluted test material, which was left under occlusion for 24 hours. After the 24 hours exposures, the sites were gently wiped with clean gauze to remove non-absorbed material. One animal died during the 15-day observation period. Consequently, LD50 was determined to be > 2000 mg/kg bw. No information is provided on possible local effects, observed clinical effects or possible differences between the groups with abrade and non-abraded skin.

Justification for classification or non-classification

The LD50 between 300 and 2000 mg/kg bw of the most recent and reliable study results to classification in Category 4 for acute oral toxicity in accordance with Regulation (EC) No 1272/2008. Acute dermal toxicity LD50 is considered > 2000 mg/kg bw on the basis of read-across with existing data on diamines compounds. There is no data available on acute toxicity via inhalation. However, related to low vp and no inhalable particles, there will be no exposure via inhalation.

No classification STOT-SE Cat.3 needed: The active substance is not structurally related to any known class of neurotoxic chemicals. Also, there is no risk for aspiration as with a melting point of 89°C, Amines, N-(C16 -18 and C18 -unsatd. alkyl)trimethylenedi-, diacetates is a solid upon ingestion.