DL-hexane-1,2-diol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

April & May 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study fulfills scientific principles and was conducted according to OECD 403 (1981) but pre-dates GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentane-1,2-diol

EC Number:

226-285-3

EC Name:

Pentane-1,2-diol

Cas Number:

5343-92-0

IUPAC Name:

pentane-1,2-diol

Constituent 2

Reference substance name:

1,2-pentanediol

IUPAC Name:

1,2-pentanediol

Test material form:

other: liquid

Details on test material:

Test substance: CGA-143816 techn.
Batch No.: CGA-143816 techn., EN 31622
Generic/trade name: 1,2-pentandiol
Purity: 95.0 %
Physical properties: slightly soluble in water
Stability: stable at room temperature
Test material received: March 16, 1982

Test animals

Species:

rat

Strain:

other: Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Husbandry: Young adult rats of both sexes (Tif: RAI f (SPF) strain), weighing 223 ± 8 g (males) and 210 ± 14 g (females), respectively, bred and raised on the premises, were used in the experiment. Before and after the inhalation exposure, the animals were maintained in an animal room at a temperature of 22 ± 2 °C, a relative humidity of 55 ± 10 % and on a 12 hour/day light cycle. The rats, segregated by sex, were group-housed (5 animals per cage) in Macrolon cages, type 4 - (Ehret, 783 Emmendingen/Germany). Rat chow (NAFAG 890 Tox, NAFAG, Gossau/SG, Switzerland)- and water were provided ad libitum.
Group Size: Each of the 2 dosage groups consisted of 20 rats (10 males and 10 females), which were approximately matched in weight. Within the groups, the animals of either sex were identified with numbers from 1 to 10 using picric acid stain on the fur. After exposure, the animals were placed in their cages, which were marked with a cage card containing the date of exposure and the characteristics of the experiment and dose group. A control group (of equal size) was exposed to an inhalation of purified air under the same condition as were used in the test material exposure.
The following environmental parameters within the inhalation chamber were monitored at approximately the same intervals as the concentration determinations:
- Temperature (with a Therm 2104 Contact Thermometer, Ahlborn Mess- und Regeltechnik, Bolzkirchen/Germany)
- Relative humidity (with a Vaisala Humidity Indicator am 11, Belag AG, 8051 Zuerich/Switzerland)
- Oxygen content (with a Draeger E 15 Stationary Control System, Draegerwerk AG, Luebeck/Germany)

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

Chamber: All exposures were conducted according to the procedure of Sachsse at al. in a nose-only exposure system with a plexiglass exposure chamber holding approximately 100 liters. For the inhalation period, the rats were placed in individual PVC-tubes positioned radially around the exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol. The chamber was maintained at a slightly negative pressure to prevent leakage of the aerosol from the system. The exhaust air was decontaminated by subsequent passage through two gas washing bottles containing 5 % NaOH.
Aerosol: The aerosol was generated by injecting the liquid test substance with a Perfusor IV Syringe System (Bender and Hobein, 8051 Zuerich, Switzerland) at a rate of 60 and 180 ml/h into a spray nozzle (JATO, Luzern, Switzerland). Through the nozzle, compressed filtered air (2 atmospheres, 10 1/min) was discharged into the inhalation chamber. The control animals were exposed to filtered air under the same conditions as described above.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The air flow through the chamber was measured with a Brooks Sho-Rate flow meter.

Duration of exposure:

4 h

Concentrations:

The aerosol concentration in the chamber was determined 5 times (after 30 minutes, 1, 2, 3, and 4 hours of exposure) by gravimetric sampling of the test atmosphere through a Selectron filter of 50 mm diameter and a pore size of 0.2 um. The air flow rate for the sample collection was 10 1/min. The means and
standard deviations of the aerosol concentration for each exposure were calculated.
Two concentrations 3380 and 7015 mg/m3 were tested next to control with clean air.

No. of animals per sex per dose:

10 males and 10 females per dose group

Control animals:

yes

Details on study design:

Animals were examined for clinical symptoms and mortalities during the exposure at 1, 2, and 4 hours, as well as 2 hours after the exposure and daily thereafter for 14 days. Body weights were recorded immediately prior to exposure and on days 7 and 14 of the observation period. Gross pathological examinations were performed on all animals dying within the 14 day observation period as well as the survivors which were killed after 14 days by asphyxiation with CO2. Particular attention was given to the respiratory tract.

Statistics:

Inhalation LC50 values including their 95% confidence limits during the 4-hour treatment and the 14 days post-exposure period could not be calculated, because no mortalities were elicited by the test substance. The body weights of the treated animals and the controls were compared by analysis of variance.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 7 015 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities occurred during exposure and during the 14 day observation period. As the limit set in the OECD guidelines (5000 mg/m3) was
exceeded, no attempt was made to generate even higher concentrations of CGA-143816.

Clinical signs:

other: Exposure to 3380 mg/m3 resulted in slight, to 7015 mg/m3 in moderate dyspnoea. Ruffled fur and curved body position were seen at both concentrations during the exposure and one day thereafter. All animals exposed to the test material recovered within 1 da

Body weight:

The body weight gains of both sexes showed a significant increase during the first observation period (day 1-7). During the second observation period, they were within normal limits.

Gross pathology:

Some of the animals exposed to the test substance exhibited mottled or reddish lungs. No other treatment-related deviations were seen.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LC50 to both sexes:greater than 7015 mg/m3 air
According to the OECD guidelines, this study may be considered a limit test, as a concentration greater than 5000 mg/m3 did not produce any mortality.

Executive summary:

Upon a 4 hour aerosol exposure and a 14 day post-treatment observation period, no mortalities could be elicited upon exposure to

CGA-143816 techn., even at the highest particle concentration tested (7015 mg/m3). It can be assumed from the absence of mortalities and the weak symptoms observed that LC50 to both sexes is greater than 7015 mg/m3 air.

According to the OECD guidelines, this study may be considered a limit test, as a concentration' greater than 5000 mg/m3 did not produce any mortality.