9-Decenamide, N,N-dimethyl-

Endpoint summary

Description of key information

Acute oral toxicity: GLP study conducted in female Sprague-Dawley rats according to OECD 425 test guideline. The statistical estimated acute oral LD50 was determined to be 550 mg/kg body weight and a 95% PL confidence interval of 265.4 mg/kg to 1520 mg/kg.
Acute dermal toxicity: GLP study conducted in rats according to OECD TG 402 using the read-across substance N,N-dimethyldecanamide. LD50 > 5000 mg/kg bw
Acute inhalation toxicity: GLP study in rats performed according to OECD TG 403 using the read across substance N,N-dimethyldecan-1 -amide, mixture with N,N-dimethyloctan-1 -amide. LC50 > 3551 mg/m3.

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:

04 February 2014 to 24 February 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to OPPTS 870.1100 and OECD 425 test guidelines.

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan, Indianapolis, Indiana
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 203 - 257 g
- Fasting period before study: overnight
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): Purina rat chow, ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark

IN-LIFE DATES: From: 04 February 2014 To: 24 February 2014

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.475 ml

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Limit dose

Doses:

2000, 550, 175 mg/kg

No. of animals per sex per dose:

3, 4, 3, females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed frequently on day of dosing and dailt thereafter for 14 days. Bodyweights taken on Days 1, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

The LD50 was calculated according to the Agency's developed software package (AOT425StatPgm) for performing the test and calculation of the LD50.

Sex:

female

Dose descriptor:

LD50

Effect level:

550 mg/kg bw

Based on:

test mat.

95% CL:

265.4 - 1 520

Mortality:

3 of 3 animals dosed with 2000 mg/kg died prematurely, 2 of 4 animals dosed with 550 mg/kg died prematurely, there were no premature mortalities in 3 animals dosed with 175 mg/kg.

Clinical signs:

other: Clinical signs were observed on the first day of dosing in all animals dosed with 550 or 2000 mg/kg.

Gross pathology:

No gross observations except for stomach and GI tract distended with gas and fluid in one animal dosed with 2000 mg/kg and one animal dosed with 550 mg/kg.

Results for the individual animals are given in the attached document.

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: US CPSC / US OSHA

Conclusions:

The statistical estimated acute oral LD50 was determined to be 550 mg/kg body weight and a 95% PL confidence interval of 265.4 mg/kg to 1520 mg/kg. Therefore the substance would be classified EPA Toxicity Category III for acute oral toxicity. According to Regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, the substance is classified as Category 4.

Executive summary:

Introduction

The substance was tested for acute oral toxicity in accordance with OPPTS Guidelines and the OECD 425 'Up and Down Method'.

Methods

The substance was administered by gavage at various dose levels according to the Up and Down procedure to female rats. Dose levels of 2000, 550 and 175 mg/kg were administered according to the software package AOT 425StatPgm.

Results

The statistical estimated acute oral LD50 was determined to be 550 mg/kg body weight and a 95% PL confidence interval of 265.4 mg/kg to 1520 mg/kg.

Conclusion

The substance would be classified as EPA Toxicity Category III for acute oral toxicity. According to Regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, the substance is classified as Category 4.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

550 mg/kg bw

Quality of whole database:

Klimisch grade 1.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to OECD guideline with GLP

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.
- Fasting period before study:
- 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 observationperiod - 20000mg/m3 Rhinarium swollen, nose r

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:

not classified

Remarks:

Migrated information Acute inhaltion toxicity tested up to max attainable conc. Criteria used for interpretation of results: other: EU GHS EC 1272/2008

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 conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

3 551 mg/m³ air

Quality of whole database:

Klimisch grade 2 (read-across)

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study according OECD guideline, GLP, well documented. Relaibility reduced due to read-across

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 were 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:

other: Pilot study: only piloerections (one male) Main study: piloerection 1 and 3 hours after application (all animals)

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:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU GHS EC 1272/2008

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 SAT 970 419 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

Quality of whole database:

Klimisch grade 2 (read-across)

Additional information

Acute oral toxicity:

In a study performed in accordance with OECD TG 425 and EPA OPPTS 870.1100, the substance was administered by gavage at various dose levels according to the Up and Down procedure to female rats [Kukulinski, 2014]. Dose levels of 2000, 550 and 175 mg/kg were administered according to the software package AOT 425StatPgm. The statistical estimated acute oral LD50 was determined to be 550 mg/kg body weight and a 95% PL confidence interval of 265.4 mg/kg to 1520 mg/kg.

In a supporting study, the acute oral toxicity in rats of the read-across substance N,N-Dimethyldecan-1-amide  (CAS No. 14433-76-2) was determined according to OECD TG 420 [Hoyer, 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.

This difference in toxicity may be explained by a difference in test procedure. In the key study, N,N-dimethyl 9 -decenamide was tested without dilution whereas in the supporting study N,N-dimethyldecan-1 -amide was diluted in distilled water and dosed at a much greater dose volume. This may have had a significant impact on the rate of absorption or on local irritation effects in the intestine.

Acute dermal toxicity:

No data on acute dermal toxicity are available for the substance. The acute dermal toxicity of the read-across substance N,N-dimethyldecanamide in rats was determined according OECD TG 402.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 piloerection and post mortem inspection revealed no abnormalities. The dermal LD50 of N,N-dimethyldecanamide in rats was found to be above 5000 mg/kg bw.

Acute inhalation toxicity:

No data for acute inhalation toxicity are available for the substance. A study for acute inhalation toxicity was conducted on a read-across substance N,N-dimethyldecan-1 -amide, mixture with N,N-dimethyloctan-1 -amide (CAS No. 67359 -57 -3) in accordance with OECD TG 403 [Pauluhn, 1991]. Five 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 maximum 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 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.

 

Justification for selection of acute toxicity – oral endpoint
GLP study conducted in female Sprague-Dawley rats according to OECD 425 test guideline.

Justification for selection of acute toxicity – inhalation endpoint
GLP study on read-across substance

Justification for selection of acute toxicity – dermal endpoint
GLP study performed on read-across substance

Justification for classification or non-classification

Acute oral toxicity:

On the basis of the acute oral LD50 of 550 mg/kg bw, the substance is classified as Acute 4 for oral toxicity (DSD Xn, R22).

Acute dermal toxicity:

Based on the LD50 > 5000 mg/kg bw available for the read-across substance N,N-dimethyldecanamide, the substance is not classified for acute dermal toxicity.

Acute inhalation toxicity:

Based on the LC50 > 3551 mg/m3 available for the read-across substance N,N-dimethyldecan-1 -amide, mixture with N,N-dimethyloctan-1 -amide, the substance is not classified for acute inhalation toxicity.