1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Octopirox

IUPAC Name:

Octopirox

Constituent 2

Reference substance name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

EC Number:

272-574-2

EC Name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Cas Number:

68890-66-4

Molecular formula:

C14H23NO2.C2H7NO

IUPAC Name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Constituent 3

Reference substance name:

Piroctone Olamine

IUPAC Name:

Piroctone Olamine

Constituent 4

Reference substance name:

1-Hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2-pyridone, 2-aminoethanol salt

IUPAC Name:

1-Hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2-pyridone, 2-aminoethanol salt

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Portage, Michigan
- Age at study initiation: 46 - 55 days
- Fasting period before study: no
- Housing: individually caged in suspended wire-mesh cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 1 °C
- Humidity (%): not stated
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 hour interval


IN-LIFE DATES: From: 1989-05-05 To: 1989-07-24

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass chambers
- Exposure chamber volume: 160 L (Group 1); 54 l (Groups 2 and 3)
- Source of air: Filtered air from in-house compressed air system
- Flow rate of air: 98 - 110 L/min
- Method of particle size determination: 8-stage cascade impactor
- Treatment of exhaust air: Discharged into foom hood

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
Group 1: 10.0 micrometer (GSD=2.10)
Group 2: 4.4 micrometer (GSD=2.20)
Group 3: 4.2 micrometer (GSD=2.07)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Group 1: 4.4 mg/L
Group 2: 4.9 mg/L
Group 3: 2.0 mg/L

No. of animals per sex per dose:

5 males + 5 females per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.9 mg/L air

Exp. duration:

4 h

Mortality:

1 male and 3 female animals from the high dose group

Clinical signs:

other: labored breathing; gasping

Body weight:

depressed

Gross pathology:

Macroscopic findings (white material in trachea, gas filled intestines, red mottled lungs, dark kidneys) only observed in animals died on study. No
abnormalities in surviving animals.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The median lethal concentration (LC50) of Octopirox after inhalation exposure is estimated to be equal-to-or-greater-than 4.9 mg/L

Executive summary:

Three groups of 5 male and 5 female Sprague-Dawley rats were exposed to a dust aerosol atmosphere of Octopirox at actual concentrations of 4.4 / 4.9 or 2.0 mg/l. The equivalent aerodynamic diameters of the test material aerosols were 10 microns for the 4.4 mg/l exposure group, 4.4 microns for the 4.9 mg/l exposure group and 4.2 microns for the 2.0 mg/l exposure group. One male and three females from the 4.9 mg/l group died either during the exposure or within 24 hours post-exposure. A high incidence of labored breathing and gasping was noted in the two groups exposed to the smaller particle size. Body weight gain was depressed except for females exposed to 2.0 mg/l. Macroscopic abnormalities observed at necropsy, white material in the trachea, gas filled intestines, red mottled lungs and dark kidneys, were only observed in those animals which died on study. No exposure related abnormalities were noted in those animals surviving 14 days. Based on this study the LC50 was estimated to be equal-to-or-greater-than 4.9 mg/l.