1,3-dihydroxyacetone

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-12-22 to 2004-05-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 1981-05-12

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

published 1992-12-29

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

August 1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

other: Limit test

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,3-dihydroxyacetone

EC Number:

202-494-5

EC Name:

1,3-dihydroxyacetone

Cas Number:

96-26-4

Molecular formula:

C3H6O3

IUPAC Name:

1,3-dihydroxyacetone

Details on test material:

Purity 99,7%

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd. Laboratory Animal Services, Fuellinsdorf, Switzerland
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Males: 9 weeks
Females: 11 weeks
- Weight at study initiation: Males: 239.6 - 251.3g
Females: 204.0 - 215.9g
- Fasting period before study:
- Housing: Groups of 5 animals of the same sex were housed in Makrolon type IV cages with wire mesh tops
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 26-51
- Air changes (per hr):
- Photoperiod: 12 hrs dark / 12 hrs light
- Music was played 12h /day mainly during light period

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

2.92 µm

Geometric standard deviation (GSD):

2.41

Remark on MMAD/GSD:

The MMAD values obtained from two gravimetric measurements of particle size distribution were similar:
Impactor 1: MMAD = 2.92 µm [2.41];
Imapctor 2: MMAD = 2.96 µm [2.43]
The MMADs were within the range of 1-4µm as recommended by Guidelines.

Details on inhalation exposure:

A dust aerosol was generated from the test item using a rotating brush aerosol generator (CR 3020, CR Equipments SA, CH-1295 Tannay, Switzerland) connected to a micronising jet mill. No diluent air was added. The generated aerosol was discharged into the exposure chamber through a 63Ni charge neutraliser.
Test atmosphere samples for the gravimetric measurements of the test item concentration and particle size distribution, and for the measurement of relative humidity, temperature and oxygen concentration, were collected directly from the feed tube in the breathing zone of the animals, at an empty port of the exposure chamber delivering "fresh" test item to the animal's nose. This approach was chosen in order to obtain representative samples of what was delivered to the animals. Airflow rates were determined for the recording of relative humidity, temperature and oxygen concentration and during the collection of samples for the determination of test item concentration using a dry-test meter and a pressure gauge (Schlumberger Industries SA, City of Geneva and Timeus & Co., Zurich, respectively), calibrated with a reference dry-test meter. Sampling airflow rates during the collection of impactor samples were determined using a calibrated pressure gauge (Timeus & Co., Zurich).

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric measurement

Duration of exposure:

4 h

Concentrations:

mean aerosol concentration = 5.114 mg/L air

No. of animals per sex per dose:

A group of 5 male and 5 female Wistar rats [HanBrl:WIST(SPF)] was used in this study.

Control animals:

no

Details on study design:

The 10 animals were exposed by nose-only, flow-past inhalation to the test item at a mean aerosol concentration of 5.114 mg/L air for a single 4-hour period. Two gravimetric measurements of particle size distribution during the exposure produced mass median aerodynamic diameters of 2.92 µm and 2.96 µm. All animals were observed for clinical signs and mortality during and following the inhalation exposure, i.e. over a 15-day observation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 4, 8 and 15. On day 15, all animals were sacrificed and necropsied.

Statistics:

No

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

LC0

Effect level:

> 5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality was observed.

Clinical signs:

other: No clinical signs were observed.

Body weight:

No relevant adverse effects on body weight development were observed.

Gross pathology:

No macroscopic pathology findings.

Other findings:

no other findings

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the data of this study, the LC50 value of the test item in rats exceed 5.114 mg/L air. No toxicity was observed in rats after inhalation of the test item up to the limit dose.

Executive summary:

The acute toxicity potential of the test item after inhalation was investigated in Wistar rats after an exposure period of 4 hours using a nose-only inhalation system. Male and female animals were exposed to the test item at a mean aerosol concentration of 5.114 mg/L air with a particle size (MMADs) of ~ 2.9 µm. No deaths, no clinical signs and no relevant adverse effects on body weight gain were observed during the 15-day observation period following exposure. Gross necropsy revealed no macroscopic pathological findings, and specifically, no lung or respiratory tract discoloration was observed.

Based on the results of this study, the LC50 of the test item in rats after single exposure by inhalation for 4 hours is >5.114 mg/L, and the test item is considered to have no toxicity potential after single administration by the inhalation route.