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Description of key information

Acute oral toxicity (rat): LD50 > 2000 mg/kg bw  (Cognis 1997)
Acute dermal toxicity (rat): LD50 > 5000 mg/kg bw (Cognis 1997)
Acute inhalative toxicity (rat): LC50 mixture of dimethylamides (mainly C8/C10): > 3551 mg/m3 (Bayer 1991)

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Tierzucht Schönwalde GmbH, Schönwalde, Germany
- Weight at study initiation: main study mean 212g male, 168g female
- Fasting period before study: 18h prior admin
- Housing: animal room 4, filtered air, transparent polycarbonate cages (macrolonge type III), two or three rats per cage
- Diet (e.g. ad libitum): Altromin 1314 (Altromin, Lage, Germany) ad libitum
- Water (e.g. ad libitum): ad libitum (acified pH=2.5 with HCl)
- Acclimation period: 15 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3°C
- Humidity (%): 55±15%
- Air changes (per hr): 10 times/h
- Photoperiod (hrs dark / hrs light): 12h each
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE: sterile distilled water
- Concentration in vehicle: 2g/10ml
- Amount of vehicle (if gavage): ca. 8ml
- Justification for choice of vehicle: common vehicle
- Purity: 100 %

MAXIMUM DOSE VOLUME APPLIED: 10ml/kg b.wt

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Sighting study show dead in the 5000mg/kg b.wt. group whereas only signs of toxicity were observerd in the 2000 mg/kg b.wt. sighting study.
Doses:
sighting study: 5000 mg/kg b.wt. (one rat), 2000 mg/kg b.wt. (one rat)
main study: 2000 mg/kg b.wt.
No. of animals per sex per dose:
main study: 5 rats per sex per dose
Control animals:
no
Details on study design:
Rats were observed 1, 3 and 6 h after administration and daily for 14 days
Body weight were recorded on day 0, 7, 14
Statistics:
no statistics
Preliminary study:
Preliminary study with one rat each for dosages of 5000mg/kg b.wt. and 2000 mg/kg b.wt. were performed.
Deads occured within the 5000mg dosing whereas signs of toxicity could be observed for the 2000mg dosing. Therefore it was decided to performe a limit test with 2000mg/kg b.wt.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
Sighting study: 5000mg/kg b.wt. the animal died
2000mg/kg b.wt. the animal survived
Main study: 2000mg/kg b.wt. no increased mortality
Clinical signs:
Sighting study: 5000mg/kg b.wt. pinched abdomen, piloerection, ataxia, comatose
2000mg/kg b.wt. pinched abdomen, piloerection
Main study: 2000mg/kg b.wt. pinched abdomen, piloerection
Body weight:
Sighting study: surviving rat has normal body weight
Main study: rats had normal body weight gain during the study period
Gross pathology:
Main study: gross necropsy revealed a gas filled intestine (three animals), distended vessel of testes in one animal, light margin of liver in two animals
Other findings:
not stated
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of N,N-Dimethyldecan-1-amide in rats was found to be above 2000 mg/kg b.wt.
Executive summary:

The acute oral toxicity in rats was determined according to the method recommended in the OECD Guideline No. 420, "Acute Oral Toxicity - Fixed Dose Method", July 1992 and the corresponding EEC GuidelineB.l bis "Acute Toxicity (Oral)", 29.12.1992.

The study was initiated with a sighting study, in which one female rat was given SAT 970 419 (N,N-Dimethyldecan-1 -amide) in a 2000 mg/kg b.wt. dose. Slight signs of toxicity were observed in this rat. Another female rat was given SAT 970 419 (N,N-Dimethyldecan-1-amide) in a 5000 mg/kg b.wt. dose. This animal died under severe signs of toxicity on day 2.

On the basis of the results from the sighting study it was decided to carry out the main study with one group consisting of five male and five female rats given a dose of 2000 mg/kg b.wt.

All animals in the main study survived the treatment and showed slight signs of toxicity (clinical signs: pinched abdomen, piloerection). Gross necropsy revealed a gas filled intestine for three animals, distended vessel of testes in one animal, light margin of liver in two animals.

Under the experimental conditions described in this report, the oral LD50 of SAT 970 419 (N,N-Dimethyldecan-1-amide) in rats was found to be above 2000 mg/kg b.wt.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann/ Borchen 7 District of Paderborn / Germany
- Age at study initiation: between 2-3 months old
- Weight at study initiation: The rats had a mean starting weight of approx. 170 to 210 g.
- Housing: Makrolon® cages type III, 5 animals per cage
- Diet (e.g. ad libitum): ad libitum ;"Altromin" 1324 Diet for Rats and Mice
- Water (e.g. ad libitum): ad libitum; tap water
- Acclimation period: at least 4 days until the start of the treatment


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° ± 2 °C
- Humidity (%): approx. 50 %
- Air changes (per hr): approx. 10 times per hour
- Photoperiod (hrs dark / hrs light): 12-hour artificial lighting from 06.00 to 18.00 hrs GET
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: unchanged for high concentration; mixture with polyethylene glycol 400 - ethanol for low concentrations
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The aerosol was sprayed under dynamic conditions into a cylindrical inhalation chamber with baffle
- Exposure chamber volume: The PVC inhalation chamber had the following dimensions: diameter = 30 cm, height = 28 cm (volume: approx. 20 liters)
- Source and rate of air/Method of conditioning air: The compressed air was produced with two in-parallel Boge compressors type SB 270/15/350D. The air was fully conditioned automatically by an in-line VIA compressed air dryer type A 110, i.e. water, dust and oil were removed.
- System of generating aerosols:The aerosol was generated by means of a nozzle (combination nozzle, Rhema Labortechnik Co.) and conditioned compressed air. A nominal 200 pi spray solution/10 liters air per min (dispersion pressure approx. 600 kPa) was nebulized under dynamic conditions into the baffle of the inhalation chamber.
- Method of particle size determination: Particle analysis was performed with an aerodynamic particle sizer with laser velocimeter (TSI-APS 3300)
- Treatment of exhaust air: outlet air was purified via a cotton wool filter
- Temperature, humidity, pressure in air chamber: temperature approx. 22 °C; relative air humidity approx. 30%


TEST ATMOSPHERE
- Brief description of analytical method used: Concentration in the test atmosphere was determined by gas chromatography (WL detector).
- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable):polyethylene glycol 400 (= PE) - ethanol mixture (mixing ration 1:1) for low concentrations
- Concentration of test material in vehicle (if applicable): approx. 10000 µL PE/m3 as an aerosol, approx. 10000 µL ethanol/m3 as a vapor)


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution/MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): see any other information

Analytical verification of test atmosphere concentrations:
yes
Remarks:
Concentration in the test atmosphere was determined by gas chromatography (WL detector)
Duration of exposure:
>= 4 h
Concentrations:
nominal: 1000; 5000; 20000; 50000 mg/m3
analytical: 118.5; 586.4; 2007.6; 3550.7 mg/m3
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 2 weeks post-treatment observation period
- Frequency of observations and weighing: Clinical signs - several times on day of exposure
- twice daily (mornig evening)
Rectal temperature - directly after exposure was completed
Body weights - before exposure; day 3 and 7
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, rectal temperature, necropsy
Statistics:
yes, different methods (Fisher's Pairwise Test, Box Test, ANOVA method etc)
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3 550.7 mg/m³ air (analytical)
Exp. duration:
4 h
Mortality:
No animals died up to and including a concentration of 20000 mg/m3 (nominal)
One male animal died on day 0 at a concentration of 50000 mg/m3 (nominal) all other animals survived the postobservation period
Clinical signs:
other: - 0mg/m3 and 1000mg/m3: All rats tolerated the treatment without clinical signs. - 5000mg/m3 Nose reddened, reduced motility, piloerection. All animals without signs from day 1 of the post-treatment observation period - 20000mg/m3 Rhinarium swollen, nose
Body weight:
A toxicologically significant influence on body weights occurred during the post-treatment observation period from 20000 mg/m3 onwards.
Gross pathology:
Rats which died intercurrently; Lung distended, liver-like and edematous; hydrothorax; nose and rhinarium reddened and swollen; spleen pale; kidneys marbled; contents of duodenum slimy-yellow.
Rats sacrificed at the end of the post-treatment observation period; Gross pathological examination revealed no evidence of specific organ changes. In 50000µL/m3 "distended lung" tended to be more prevalent amongst the animals.
Other findings:
A toxicologically significant hypothermia was determined at the end of exposure from group 3 (5000 mg/m3 air)

ASSESSMENT AND DISCUSSION:

The test substance as an aerosol proved to have a relatively low acute inhalative toxicity in the rat up to the maximum tested concentration of 3551 mg/m3 air.

A single 4-hour exposure to 3551 mg/m3 air resulted in relatively persistent respiratory disorders considered to be causally related to a primary irritant effect on the respiratory tract. The hypothermia determined from 586.4 mg/m3 air is considered to be causally related to the aerosol's local irritant potential.

Interpretation of results:
GHS criteria not met
Conclusions:
LC50 inhalation (aerosol) Rat (exposure: 4 h) > 3551 mg/m3 air
Executive summary:

A study for acute inhalation toxicity was conducted with "confidential substance name" in accordance with OECD Guideline No. 403.

Therefore 5 SPF-bred Wistar rats were exposed (head/nose only) to 118.5; 586.4; 2007.6 and 3550.7 mg/m3 (analytical determined).

Rats subjected to a concentration of 119 mg/m3 air tolerated the exposure without signs occurring. Rats exposed to 586 mg/m3 air exhibited a transient reddening of the nose on the day of exposure and reduced motility. Rats subjected to the max. tested concentration (3551 mg/m3 air; nebulization of the undiluted test article) exhibited persistent signs causally linked to an irritation of the respiratory tract (slower breathing, serous nasal discharge, dyspnea, stridor, hypothermia). 3551 mg/m3 air was the range at which mortality started for male rats (1 of 5 died). The results of this study show that the respirable test article aerosol had a relatively low acute inhalative toxic effect on the rat. The acute potential hazard of the respiratory tract is attributed to the potency of the test substance aerosol to act as a mucosa irritant. LC50 inhalation (aerosol) Rat (exposure: 4 h) > 3551 mg/m3 air

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
see attached RA justification
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3 550.7 mg/m³ air (analytical)
Exp. duration:
4 h
Interpretation of results:
GHS criteria not met
Conclusions:
LC50 inhalation (aerosol) Rat (exposure: 4 h) > 3551 mg/m3 air
Executive summary:

A study for acute inhalation toxicity was conducted with "analog test item" in accordance with OECD Guideline No. 403.

Therefore 5 SPF-bred Wistar rats were exposed (head/nose only) to 118.5; 586.4; 2007.6 and 3550.7 mg/m3 (analytical determined).

Rats subjected to a concentration of 119 mg/m3 air tolerated the exposure without signs occurring. Rats exposed to 586 mg/m3 air exhibited a transient reddening of the nose on the day of exposure and reduced motility. Rats subjected to the max. tested concentration (3551 mg/m3 air; nebulization of the undiluted test article) exhibited persistent signs causally linked to an irritation of the respiratory tract (slower breathing, serous nasal discharge, dyspnea, stridor, hypothermia). 3551 mg/m3 air was the range at which mortality started for male rats (1 of 5 died). The results of this study show that the respirable test article aerosol had a relatively low acute inhalative toxic effect on the rat. The acute potential hazard of the respiratory tract is attributed to the potency of the test substance aerosol to act as a mucosa irritant. LC50 inhalation (aerosol) Rat (exposure: 4 h) > 3551 mg/m3 air

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
3 551 mg/m³

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
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: Tierzucht Schönwalde GmbH, Schönwalde, Germany
- Weight at study initiation: weight on dosing day 192-252g
- Fasting period before study: not fasted prior dosing
- Housing: animal room 4, filtered air, transparent polycarbonate cages (macrolonge type III), two or three rats per cage
- Diet (e.g. ad libitum): Altromin 1314 (Altromin, Lage, Germany) ad libitum
- Water (e.g. ad libitum): ad libitum (acified pH=2.5 with HCl)
- Acclimation period: 36 days (female), 8 days (male)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±3°C
- Humidity (%): 55±15%
- Air changes (per hr): 10 times/h
- Photoperiod (hrs dark / hrs light): 12h each
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 5*6cm
- coverage: 4-layer gauze
- Type of wrap if used: Micropore tape wounded around the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): sponged with lukewarm water
- Time after start of exposure: 24h

TEST MATERIAL
- Constant volume or concentration used: constant dose of 5000mg/kg b.wt.

Duration of exposure:
24h
Doses:
Pilot study: 2000 and 5000 mg/kg b.wt.
Main study: 5000 mg/kg b.wt.
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
according to guideline
Statistics:
no
Preliminary study:
Pilot study: no abnormalities observed at the animal dosed with 2000 mg/kg b.wt.
piloerection was observed at the animal dosed with 5000 mg/kg b.wt.
Therefore main study was accomplished with 5000 mg/kg b.wt.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
Pilot study: no deaths observed
Main study: no deaths observed
Clinical signs:
Pilot study: only piloerections (one male)
Main study: piloerection 1 and 3 hours after application (all animals)
Body weight:
Pilot study: normal body weights during the study
Main study: some females show stagnation in body weight increase all other rats had normal body weight gain
Gross pathology:
Pilot study: post mortem inspection revealed no abnormalities
Main study: post mortem inspection revealed no abnormalities
Other findings:
not stated
Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions the dermal LD50 of N,N-Dimethyldecan-1-amide in rats was found to be above 5000mg/kg b.wt.
Executive summary:

The acute dermal toxicity of N,N-Dimethyldecan-1-amide in rats was determined according to the method recommended in the OECD Guideline No. 402 "Acute Dermal Toxicity", Feb. 1987, and the corresponding EEC GuidelineB.3 "Acute Toxicity (Dermal)", 29.12.92.

The study was performed as a limit test with 10 Wistar rats (five males and five females). The rats were exposed to a single dermal dose of 5000 mg/kg b.wt. for 24 hours followed by an observation period of 14 days. During the study clinical signs of reaction to the treatment were recorded daily. Body weight was recorded once a week. After the two week observation period the animals were killed and subjected to a gross necropsy examination.

All animals in the main study survived the treatment and showed very slight signs of toxicity.

Under the experimental conditions described in this report, the dermal LD50 of the test substance in rats was found to be above 5000 mg/kg b.wt.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Additional information

Valid data is available for the assessment of acute oral and acute dermal toxicity of N,N-Dimethyldecanamide. Acute inhalation toxicity was tested with a mixture of N,N-dimethyldecanamide and N,N-dimethyloctanamide (with traces of N,N-dimethyl-dodecanamide and N,N-dimethyl-hexanamide). Due to the fact that a high amount in the mixture was N,N-dimethyl-decanamide and the rest of the mixture are homologues with a lower and higher molecular weight which can be assumed to have a similar toxicological behaviour it is concluded that the mixture has an nearly similar toxicological behaviour like pure N,N-dimethyldecanamide, further details can be found in the attached RA justification in chapter 13.

Acute oral toxicity (N,N-dimethyldecanamide):

The acute oral toxicity in rats was determined according to OECD Guideline No. 420 (Cognis 1997).The study was initiated with a sighting study, in which one female rat was given N,N-Dimethyldecan-1 -amide in a 2000 mg/kg bw dose. Slight signs of toxicity were observed in this rat, therefore another female rat was given N,N-Dimethyldecan-1-amide in a 5000 mg/kg bw dose. This animal died under severe signs of toxicity on day 2.On the basis of the results from the sighting study it was decided to carry out the main study with one group consisting of five male and five female rats given a dose of 2000 mg/kg bw.All animals in the main study survived the treatment and showed slight signs of toxicity (clinical signs: pinched abdomen, piloerection). Gross necropsy revealed a gas filled intestine for three animals, distended vessel of testes in one animal, light margin of liver in two animals.

The oral LD50 of N,N-Dimethyldecan-1-amide in rats was found to be above 2000 mg/kg bw.

Acute dermal toxicity (N,N-dimethyldecanamide):

The acute dermal toxicity of N,N-dimethyldecanamid in rats was determined according OECD Guideline No. 402 (Cognis 1997).The study was performed as a limit test with 10 Wistar rats (five males and five females). The rats were exposed to a single dermal dose of 5000 mg/kg bw for 24 hours followed by an observation period of 14 days. During the study clinical signs of reaction to the treatment were recorded daily. Body weight was recorded once a week. After the two week observation period the animals were killed and subjected to a gross necropsy examination. All animals in the main study survived the treatment and showed very slight signs of toxicity. Some females show stagnation in body weight increase all other rats had normal body weight gain. Clinical signs were only piloerections and post mortem inspection revealed no abnormalities. The dermal LD50 of N,N-dimethyldecanamidin rats was found to be above 5000 mg/kg bw.

Acute inhalation toxicity (mixture of dimethylamides):

A study for acute inhalation toxicity was conducted with "confidential substance name" in accordance with OECD Guideline No. 403 (Bayer 1991). Therefore 5 SPF-bred Wistar rats were exposed (head/nose only) to 118.5; 586.4; 2007.6 and 3550.7 mg/m3 (analytical determined).Rats subjected to a concentration of 119 mg/m3 air tolerated the exposure without signs occurring. Rats exposed to 586 mg/m3 air exhibited a transient reddening of the nose on the day of exposure and reduced motility. Rats subjected to the max. tested concentration (3551 mg/m3 air; nebulisation of the undiluted test article) exhibited persistent signs causally linked to an irritation of the respiratory tract (slower breathing, serous nasal discharge, dyspnea, stridor, hypothermia). 3551 mg/m3 air was the range at which mortality started for male rats (1 of 5 died). The results of this study show that the respirable test article aerosol had a relatively low acute inhalation toxicity in the rat. The acute potential hazard of the respiratory tract is attributed to the potency of the test substance aerosol to act as a mucosa irritant.LC50 inhalation (aerosol) Rat (exposure: 4 h) > 3551 mg/m3 air.

It must also be noted that such a high concentration of 3551 mg/m3 (analytically determined) is created by a nominal concentration of 50000 mg/m3

Key study assignment:

As there is only one reliable and relevant study available for each endpoint, this study has been used as key study.

Justification for classification or non-classification

The available data for N,N-dimethyldecanamide and mixtures containing large amounts of N,N-dimethyldecanamide as well as shorter and longer homologues indicate a low potential for acute toxicity.

The available study indicate an oral LD50 (rat) > 2000 mg/kg bw (Cognis 1997) for male and female rats. Therefore N,N-dimethyldecanamide has not classified for acute oral toxicity according to GHS (Regulation (EU) 1272/2008) and also not classified according to EU-criteria DSD (67/548/EEC).

As the LD50 (rat) for acute dermal toxicity was >5000 mg/kg bw (Cognis 1997) and no death occurred, N,N-dimethyldecanamide has not to be classified acute dermal toxicity according to GHS (Regulation (EU) 1272/2008) and also not classified according to EU-criteria DSD (67/548/EEC)

As an acute inhalation toxicity test with a mixture of dimethylamides (main components N,N-dimethyloctanamide, N,N-dimethyldecanamide, Bayer 1991) reveals only one death in the highest administered concentration of 3551 mg/m3air, which reflexes the maximum attainable concentration (due to physical properties; nominal concentration 50000 mg/m3), the mixture has to not to be classified for acute inhalation toxicity according to GHS (Regulation (EU) 1272/2008) and EU-criteria DSD (67/548/EEC).

This classification is also assumed for pure N,N-dimethyldecanamide (see discussion).

Labelling for acute toxicity :

GHS: no classification

DSD: no classification