3,5-dimethylpyridine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 May 2004-3 January 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,5-dimethylpyridine

EC Number:

209-708-6

EC Name:

3,5-dimethylpyridine

Cas Number:

591-22-0

Molecular formula:

C7H9N

IUPAC Name:

3,5-dimethylpyridine

Test material form:

other: liquid

Details on test material:

3,5-Lutidine. > 98% purity. Batch #09427 TA. Expiration date: 15 March 2008. clear light yellow liquid

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10 weeks
- Weight at study initiation: males: 192-216 g, females: 138-147 g
- Fasting period before study: no data
- Housing: singly housed in suspended stainless steel cages with mesh floors. Litter paper was placed beneath the cage and was changed at least 3 times weekly.
- Diet (e.g. ad libitum): Purina Rodent Chow # 5012
- Water (e.g. ad libitum): ad libitum, tap water supplied by an automatic water dispensing system except during exposure.
- Acclimation period: 6-7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: 18 Aug 2004 To: 1 September 2004

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

A nose-only inhalation chamber with an internal volume of approximately 6.7 liters (Mini Nose-Only Inhalation Chamber, ADG Developments LTD) was used for exposure. Animals were individually housed in polycarbonate holding tubes which seal to the chamber with an “O” ring during exposure. The base unit terminates the chamber with a 0.5-inch diameter tube for discharged air. Filtered air was supplied to the spray atomization nozzle. Compressed airflow was measured using a Mass Flowmeter (Omega, Model #FMA 5613). Additional compressed mixing air was supplied directly to the exposure chamber from a conditioned ambient source. Room airflow was measured with a Mass Flowmeter (Omega, Model #FMA 5613). Breathing chamber airflow was monitored throughout the exposure period and recorded periodically.

The temperature and relative humidity within the chamber as well as the room were monitored continuously during each exposure. In-chamber measurements were made with a Humidity-Temperature Indicator (Taylor, Model #5502) and room conditions were measured with a Temperature-Humidity Monitor (Dickson, Model #TH550). Temperature and humidity values were recorded every 15 minutes for the first hour of exposure and every 30 minutes thereafter.

Vapour of the test substance was generated in a 250 ml glass graduated cylinder using filtered compressed air (approximately 20 Lpm @ 30 psi). The test substance was metered with a syringe pump (Harvard apparatus, Model #22) fitted with a 100 ml glass syringe (Perfektum). The vapor traveled to the exposure chamber from this mixing chamber. During vapour generation and transmission, the cylinder was placed in a heated water bath (~38°C) to prevent condensation of the test vapour in the delivery tube. For vapour concentration determination, five samples per exposure level were collected in sorbent tubes (Chromosorb-106, SKC Inc, Model #226-111A) connected to the breathing zone of the animals during each exposure. Each air sample was collected for 15 or 20 minutes at a flow rate of 0.5 Lpm. Sample airflows were measured using a Mass Flowmeter (Omega, Model #FMA 5610). The samples were analyzed by a GLC analysis procedure; the results of this study are based on these analytical evaluations.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

by Gas Liquid Chromatography (GC)

Duration of exposure:

4 h

Concentrations:

675.36 ppm (equivalent to 2.97 mg/L or 2970 mg/m3) and 264.26 ppm (equivalent to 1.16 mg/L or 1160 mg/m3).
Nominal concentrations were 4239 ppm (18.58 mg/L) and 1353 ppm (5.93 mg/L).

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 observations and weighing: individual body weights were recroded prior to exposure and on days 7 and 14 or after death. Observations for mortality took place during exposure periods. Following exposures, animals were examined for signs of gross toxicity and behavioral changes when removed from the chambers, and at least once daily for up to 14 days.
- Necropsy of survivors performed: yes. Euthanasia was by CO2 asphyxiation.
- Other examinations performed: clinical signs, body weight. Tissues and organs of the thoracic and abdominal cavities were examined.

Statistics:

none

Results and discussion

Preliminary study:

An initial 4-hour exposure to test material vapour of 675.36 ppm (2.97 mg/L) by 5 male and 5 female rats resulted in the death of all 10 animals at the end of the exposure period. Gross necropsy of the decedents revealed slightly to extremely red lungs and/or pulmonary edema.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.16 - < 2.97 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Two females among 10 animals died by the end of the exposure period. There were no other deaths within the 14 day observation period.

Clinical signs:

other: Surviving animals exhibited irregular respiration, hunched posture and hypoactivity. Resolution of clinical signs occured by Day 2. All surviving animals appeared active and healthy during the remaining observation period.

Body weight:

Body weight increased over the 14 day observation period.

Gross pathology:

Necropsy revealed moderately red and slightly edematous lungs.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information falls within Category 3 according to CLP. Criteria used for interpretation of results: EU

Conclusions:

The test substance displays a LC50 of > 1.16 mg/L after a 4 h exposure in male and female rats. A higher concentration of approximately 3 mg/L results in 100% lethality. The classification of the substance spans 2 categories (II and III), according to Regulation EC No. 1272/2008.