1,1',1''-nitrilotripropan-2-ol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Respiratory effects of a synthetic metalworking fluid and its components

Author:

Detwiler-Okabayashi KA, Schaper MM

Year:

1996

Bibliographic source:

Arch Toxicol 70, 195-201

Materials and methods

Principles of method if other than guideline:

Mice were exposed to 329-1070 mg/m3 TIPA (4 mice/concentration) for 3 hours. Breathing frequency was determined using a body plethysmograph and RD50 (concentration capable of evoking a 50% decrease in mean breathing frequency) was calculated.

GLP compliance:

no

Test type:

other: respiratory irritation

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,1',1''-nitrilotripropan-2-ol

EC Number:

204-528-4

EC Name:

1,1',1''-nitrilotripropan-2-ol

Cas Number:

122-20-3

Molecular formula:

C9H21NO3

IUPAC Name:

1-[bis(2-hydroxypropyl)amino]propan-2-ol

Test animals

Species:

mouse

Strain:

Swiss Webster

Sex:

male

Details on test animals or test system and environmental conditions:

Specific pathogen-free, male, Swiss-Webster mice were obtained from Hilltop Lab Animals (Scottdale, Pa., USA). They were housed in polypropylene cages, four per cage, with food (Laboratory Rodent Diet 5001, PMI Feeds, Richmond, Ind., USA) and water ad libitum. The cages were kept in an animal room which was held at a temperature of 70-72 °F, at 40-50% relative humidity, and on a 12-h dark/light cycle. A new group of four mice, each weighing 24-28 g, was used for each experiment.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Remarks:

unchanged (no vehicle)

Mass median aerodynamic diameter (MMAD):

>= 1 - <= 2 µm

Geometric standard deviation (GSD):

ca. 2

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass exposure chamber connected to four body plethysmographs. A mouse was placed in each plethysmograph such that its head extended into the interior of the chamber. A latex collar served as a seal around the neck of each mouse and held its head in place.
- Exposure chamber volume: 2.5 L
- Rate of air: 20 L/min
- System of generating particulates/aerosols: Pitt No. 1 or Pitt No. 4 aerosol generator
- Method of particle size determination: Marple personal cascade impactor (Model 290, Andersen Samplers, Atlanta, Ga., USA)

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric analysis of air samples drawn at 2 L/min onto glass fiber filters.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD: 1-2 µm; gsd: approximately 2

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric analysis

Duration of exposure:

ca. 3 h

Concentrations:

329 - 1070 mg/m3

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

Mice were exposed to 329-1070 mg/m3 TIPA (4 mice/concentration) for 3 hours. Breathing frequency was determined using a body plethysmograph and RD50 (concentration capable of evoking a 50% decrease in mean breathing frequency) was calculated. Animals were given a recovery period of 20 min. in the plethysmograph (air alone) and kept for 1 week. Breathing frequency before, during and after exposure was recorded. Breathing pattersn were analyzed for sensory and pulmonary irritation. Mortalities were recorded during the 1 week observation period.

Statistics:

Using mean responses, the maximum decrease in respiratory frequency (Fr) that occurred during the 180 min exposure was determined with respect to control. A paired t-test (p < 0.05) was used to test for significance. When significant decreases in Fr were found, they were examined as a function of the logarithm of exposure concentration. Least-squares regression analysis was then conducted to develop concentration-response relationships (i.e. testing that the slope of the line was significantly different from zero, p < 0.05) (Armitage 1977). These relationships were used to calculate the exposure concentration resulting in a 50% decrease in mean Fr of exposed mice (i.e RD50) (Alarie 1973). At the time when this 50% decrease in mean Fr occurred, the individual respiratory patterns of mice were examined to identify the predominant type of irritation, sensory (S) or pulmonary (P). The RD50 was classified as RD50S if there was predominantly sensory irritation this time or RD50P if there was predominantly pulmonary irritation at this time (Krystofiak and Schaper 1995; Schaper and Detwiler-Okabayashi 1995).

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

other: RD50 (calculated)

Effect level:

ca. 815 mg/m³ air

95% CL:

ca. 570 - 1 069

Exp. duration:

3 h

Effect levels 2

Sex:

male

Dose descriptor:

LC0

Effect level:

1 070 mg/m³ air

Exp. duration:

3 h

Mortality:

No mortality occured

Body weight:

No data

Gross pathology:

No data

Other findings:

Exposure to TIPA caused sensory irritation (immediate onset) and pulmonary irritation (delayed onset). RD50 (+95% CI) was calculated to be 815 (570-1069) mg/m3. Post-exposure recovery of the breathing frequency was moderate to good.