Propan-1-ol

Acute Toxicity: inhalation

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:

comparable to guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Three groups, each containing 5 male and 5 female rats, were exposed once for 4 hours to vapour atmospheres dynamically generated from liquid n-propyl alcohol. No control (air-only) exposures were performed. Within a post-exposure window of 14 days, animals were checked for mortality and clinical signs of toxicity. Body weights were also monitored. At conclusion, animals were sacrificed for the purpose of necropsy. Gross pathology was performed

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Propan-1-ol

EC Number:

200-746-9

EC Name:

Propan-1-ol

Cas Number:

71-23-8

Molecular formula:

C3H8O

IUPAC Name:

propan-1-ol

Test material form:

liquid

Specific details on test material used for the study:

- Source: Union Carbide chemicals and Plastics Company Inc., Texas City, TX
- Analytical purity: >= 99.8%
- Lot No. 1341206
- Container No: TX100LY69
- Supplier No.: 662329
- Storage: RT
- Stability: guaranteed by supplier when stored under ambient conditions

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Harlan Sprague-Dawley, Inc., Indianapolis, IN
- Age at study initiation: 44-56 days
- Average weight at study initiation: see table 1, below
- Housing: 1 rat/sex/cage
- Diet: ad libitum, except during exposure; pelleted feed (Pro Lab RMH #3000, Agway, Inc.)
- Water: ad libitum, except during exposure, tap water (automatic watering system)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglas chamber, cuboidal shaped
- Exposure chamber volume: 120 L
- Temperature in chamber: about 25 °C
- Relative humidity in chamber during exposure: 45-46%
- Temperature for the development of vapour: 50-66°C
- FMI pump type: RP-g20 with 1/8 inch piston head
- Airflow Measurement : A flowmeter was used to control the flow of air supplied to the exposure chamber. The flowmeter was calibrated using a Singer dry test meter
- Airflow rate: 30 l/min

For the dynamic exposures, liquid n-propyl alcohol was metered from a piston pump (Fluid Meterins Inc ., Oyster day, NJ) into a heated evaporator. The resultant vapour was diluted and carried into the chamber by a stream of filtered compressed air. Prior to entering the evaporator, the air stream for the 5185 ppm exposure was humidified by passing the air over the head space of a 5l-gallon bottle containing water.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

(Perkin-E.lmer Sigma 2000 gas chromatograph (CC) equipped with a FID was used to monitor the n-propyl alcohol exposure chamber atmospheres)

Duration of exposure:

4 h

Remarks on duration:

Single dose expsoure. Vapour concentration of test substance in chamber was dynamic

Concentrations:

Experiment 1: 5185 ppm (12.9 mg/l) (12930 mg/m3)
Experiment 2: 9741 ppm (24.3 mg/l) (24291.9 mg/m3)
Experiment 3: 13548 ppm (33.8 mg/l) (33785.7 mg/m3)

Conversion of ppm to mg/l was performed using conversion tables given in Toxicologist Pocket Handbook, CRC, 2000

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of weighing: before exposure, on day 7 and at termination
- Frequency of observation: day of exposure then thereafter, daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, complete necropsy
- Rationale for target concentrations: The target concentrations for the 5185 and 9741 ppm dynamic exposures were 5000 and 10000 ppm, respectively. These concentrations were based on toxicity data obtained from a previous acute inhalation study conducted at BRRC (report No. 16-71). The target concentration for the 13548 ppm dynamic exposures was 15000 ppm. During preliminary test without animals, aerosol formation was observed at 25°C at concentrations higher than 15000 ppm

Statistics:

The mean and standard deviation of the body weights, body weight changes, and exposure concentrations were calculated. No statistical comparisons were made. The LT50 was determined by the moving average method of Thompson (1947) for males, females, and the combined sexes using the 6-hour and 4-hour static exposure groups.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 33.8 other: mg/ l (13548 ppm) (33785.7 mg/m3)

Exp. duration:

4 h

Remarks on result:

other: No mortality was observed. Nasal, respiratory, eye irritation as well as hypoactivity, were noticed. Narcosis was seen within 2.5h. Other symptom included, prostration, and reduced pain reflex, absence of surface right reflexes

Mortality:

No deaths occured

Clinical signs:

other: 5165 ppm: Clinical signs during the 4-hour vapour exposure were periocular wetness, blepharospasm, and hypoactivity. No clinical signs of toxicity were observed on the same day following exposure or during the 14-day postexposure observation period. 9741

Body weight:

Mean body weight gain was observed for both sexes of all groups at both 7 and 14 days following exposure

Gross pathology:

There were no gross pathologic lesions observed at necropsy

Any other information on results incl. tables

Table 1: Body weight and body weight change after single dose exposure of rats with dynamic concentrations of n-propanol for 4h and a post observation period of 14 d

		Mean body weight (g) (n=5)			Mean body weight change (g) (n=5)
Dose	Sex	0	7 d	14 d	7d	14d
5185 ppm	Male	240 ± 6	275 ± 10	305 ± 7	35 ± 4	65 ± 3
	Female	157 ± 7	175 ± 3	189 ± 4	17 ± 6	32 ± 7
9741 ppm	Male	248 ± 6	280 ± 4	307 ± 6	31 ± 5	59 ± 7
	Female	158 ± 7	179 ± 9	192 ± 8	21 ± 4	33 ± 5
13548 ppm	Male	262 ± 8	281 ± 13	307 ± 15	19 ± 6	45 ± 7
	Female	175 ± 7	191 ± 11	204 ±14	16 ± 5	29 ± 8

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met