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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No OECED guideline or GLP defined; all essential data reported.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
The acute toxicity and primary irritancy of N-Benzyl-N,N-Dimethylamine
Author:
Ballantyne B, Dodd DE, Nachreiner, Myers RC
Year:
1985
Bibliographic source:
Drug and Chemical Toxicology, 8; 43-56 (1985)
Reference Type:
other: microfiche
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Principles of method if other than guideline:
In order to determine a 4-hours LC50 value, groups of animals were exposed to target test substance vapor concentrations of 500, 277, 150, and 25 ppm. For each concentration 6 male and 6 female rats were used. A control group (2/sex) was exposed to filtered air only. Animals were observed for signs of toxicity during exposure and daily during a 14-day postexposure period. Animals that died and survivors sacrificed at the end of the postexposure period were subjected to autopsy.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:



10.00 Torr at 55°C
50.00 Torr at 91°C
Flash Point: 57°C (Cleveland Open Cup)
Solubility: Readily soluble in aqueous acids, methanol, acetone and benzene. Water solubility, 0.12 g/dl.
Specific Gravity: 0.89 (25°C)
Saturated Vapor Concentration: 14430 mg/m³ (25°C)
Conversion Factors: 1 ppm= 5.53 mg/m³ (25°C, 760 Torr)
1 mg/m³= 0.181 ppm (25°C, 760 Torr)

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: 7-8 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°F) 68-80
- Humidity (%): 39-65
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Exposures were conducted in 4.35 m³ chambers constructed of stainless steel and glass, with an airflow of 1200 liters/min. Vapor was generated by the metered delivery of liquid test substance from a motorized syringe into a glass evaporator, heated gently and sufficiently to vaporize the liquid.
Chamber inlet air was passed countercurrent to the flow of liquid test substance into the evaporator. Each chamber was sampled at least five times during the 4-hours exposure period, and the atmospheric concentration of the test substance estimated by a Perkin Elmer 3920B gas chromatograph equipped with a flame ionization detector.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
24ppm: 133(+-39), 139 ppm: 769(+-199), 277 ppm: 1532(+-199), 501 ppm: 2771(+-249) mg/m³
No. of animals per sex per dose:
6 animals (2 controls)
Control animals:
yes
Details on study design:
The acute inhalation toxicity of the test substance was studied by 4-hours exposures to differing concentrations of test substance vapor in the chamber atmosphere.
In order to determine a 4-hours LC50 value, groups of animals were exposed to target test substance vapor concentrations of 500, 275, 150, and 25 ppm. For each concentration 6 male and 6 female rats were used. A control group (2/sex) was exposed to filtered air only.
Animals were observed for signs of toxicity during exposure and daily during a 14-day postexposure period. Body weights were determined for each animal just before inhalation exposure, and then on days 1, 3, 6 and 14 postexposure. Animals that died and survivors sacrificed at the end of the postexposure period were subjected to autopsy. Nasal turbinates, larynx, trachea, bronchi and lungs were removed (2/sex) and fixed in neutral buffered 10% formaldehyde, and hematoxylin-eosin stained paraffin sections examined by light microscopy.
Statistics:
moving average method

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 2 052 mg/m³ air
95% CL:
1 720 - 2 472
Exp. duration:
4 h
Remarks on result:
other: based on death of all rats at 500 ppm and no deaths in all other groups; clinical signs included irritation, salivation and labored breathing and pathol. changes in lungs and the upper resp tract at 500 and 277 ppm
Mortality:
2771 mg/m³. all male and females within 2-2.5 hours during exposure
1532 mg/m³: no deaths
769 mg/m³: no deaths
133 mg/m³: no deaths
Clinical signs:
2771 mg/m³. signs of irritation within 1.5 hrs of the start of exposure: excess salivation, labored breathing, urogenital wetness
1532 mg/m³: salivation, labored breathing, urogenital wetness; during 14-day post exposure periorbital and perinasal red encrustation
769 mg/m³, 133 mg/m³: salivation, labored breathing, urogenital wetness
Body weight:
Rats from all groups did not have any significant adverse effects on body weight gain
Gross pathology:
500 ppm (ca 2771 mg/m³): red patchy coloration of lungs, pulmonary congestion epithelial cell vacuolation and necrosis
277 ppm (ca 1532 mg/m³): pulmonary congestion, acute inflammatory changes in the nasal mucosa
139 ppm (ca 769 mg/m³), 24 ppm(ca 133 mg/m³): no gross or histopathological changes

Any other information on results incl. tables

RS-Freetext:
Signs of toxicity (time after start of exp.):
irritation (1.5 h), excess salivation, labored breathing, urogenital wetness, red periorbital and perinasal incrustations at concentrations of 769 mg/m³ and higher

Body weight (before and 1,3,6,14 d after exp.):
No significant decrease in surviving animals

Mortality:
All animals of the highest dose group died within 1 day.
LC50 = 2052mg/m³ (1720-2472)

Gross necropsy:
Red patchy discoloration of lungs in dead animals. No abnormal findings in survivors.

Microscopic examination of respiratory tract:
2771 mg/m³: pulmonary congestion and epithelial vacuolisation and necrosis of nasal mucosa in both males and females
1532 mg/m³: pulmonary congestion in males and females; acute inflammation in the nasal mucosa in male rats.
Lower doses: no abnormal findings

Applicant's summary and conclusion

Executive summary:

The acute inhalation toxicity of the test substance was studied in groups of 6 male and 6 female F344 rats per concentration

by 4-hours exposures to 25, 150, 277, 500 ppm (133, 769, 1532, 2771 mg/m³). A control group (2/sex) was exposed to filtered air only. Mortalities occurred at the highest concentration only, with all animals dying within 2 to 2.5 hours from the start of the exposure. Signs of toxicity included irritation, salivation labored breathing and urogenital wetness. During the 14 day postexposure, periorbital and perinasal red encrustations were observed and pathol. changes determined in lungs and the upper resp tract at 500 and 277 ppm

The LC50 was determined to be 373 ppm/4h (2052 mg/m³/4h, Ballantyne 1985)