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Toxicological information

Acute Toxicity: inhalation

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Chemical name: mixture of N,N-Dimethydecan-1-amide and N,N-Dimethyloctan-1-amide
Batch No: 903069
Storage: room temperature / in darkness
Vapor pressure: 0.01 kPa (at 25 °C)
Saturation cone.: 690 mg/m3 air (at 25 °C)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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

Administration / exposure

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)

Results and discussion

Effect levels
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)

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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