Tar bases, coal, lutidine fraction

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

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:

- Principle of test: 10 rats were exposed nose-only to target concentrations of 1.0 or 3.75 mg/L (200 or 750 ppm) of the test substance for a single 4-hour period and then maintained for a 14-day observation period.
- Short description of test conditions: The atmospheres were generated using a concentric jet glass atomiser and Gage cyclone into a 2-tiered PERSPEX exposure chamber. The test substance was delivered to the atomiser using a peristaltic pump.
Ten male and ten female rats (approximately 7 weeks old) were randomly assigned to two experimental groups, each comprising 5 males and 5 females. The animals were exposed to the target concentrations for a single period of 4 hours and then observed over a period of 14 days.
The total particulate concentration of each test atmosphere was measured gravimetrically, but the particle size distribution of the aerosol was not measured because of the low particulate concentrations. The test atmospheres were analysed for the test substance using an adsorption tube containing CARBOTRAP (40-60 mesh) to initially trap the material. The test substance was then thermally desorbed from the tube into a gas chromatograph equipped with a flame-ionisation detector.
- Parameters analysed / observed: Animals were observed for gross abnormalities during exposure and were then given a regular detailed examination after exposure. Bodyweights were also regularly recorded. On day 15, the animals were humanely killed and subjected to a macroscopic examination. Lungs (with trachea), liver and kidneys were removed and weighed and stored in 10% neutral buffered formol saline.

GLP compliance:

no

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tar bases, coal, lutidine fraction

EC Number:

293-766-2

EC Name:

Tar bases, coal, lutidine fraction

Cas Number:

91082-52-9

IUPAC Name:

Tar bases, coal, lutidine fraction

Test material form:

liquid

Test animals

Species:

rat

Strain:

other: Alpk:APfsD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: colony maintained in the laboratory at Alderley Park, Cheshire, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 7 weeks
- Weight at study initiation: not reported
- Fasting period before study: not reported
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 2-tiered PERSPEX exposure chamber
- Exposure chamber volume: not reported
- Method of holding animals in test chamber: not reported
- Source and rate of air: not reported
- Method of conditioning air: not reported
- System of generating particulates/aerosols: atmospheres were generated using a concentric jet glass atomiser and Gage cyclone into the exposure chamber
- Method of particle size determination: particle size distribution was not measured because of the low particulate concentrations
- Treatment of exhaust air: not reported
- Temperature, humidity, pressure in air chamber: not reported

TEST ATMOSPHERE
- Brief description of analytical method used: atmospheres were generated using a concentric jet glass atomiser and Gage cyclone into the exposure chamber
- Samples taken from breathing zone: no

VEHICLE
- Not applicable

TEST ATMOSPHERE
- Particle size distribution: not determined

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1 and 3.75 mg/L (corresponding to 200 and 750 ppm)

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: During exposure and detailed assessment after exposure on Day 1, 2, 3, 8 and 15, on the other days animals were checked
- Frequency of weighing: On days -1, 2, 3, 8 and 15
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 3.61 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There were no deaths.

Clinical signs:

other: Abnormalities recorded during exposure were salivation, very reduced response to sound, increased breathing depth and decreased breathing rate. Immediately after exposure, other abnormalities seen were reduced righting reflex, reduced stability, reduced h

Body weight:

There was an initial bodyweight loss seen on day 2 in both groups following exposure on day 1, which was greater in animals exposed to 3.61 mg/L. Males and females exposed to 3.61 mg/L and females exposed to 1.05 mg/L also lost weight on day 3. The weight loss in the top dose animals was statistically significant when compared with control rats of the same age and strain. Thereafter the rate of bodyweight gain was similar to that seen in control rats of the same age and strain.

Gross pathology:

There was a slight decrease in liver weight and liver:bodyweight ratio in males exposed to 3.61 mg/L, when compared with control rats of the same strain and age. There were no significant effects on lung weight, kidney weights, lung:bodyweight or kidney:bodyweight ratios. Changes seen at post mortem were part of the normal spectrum of background change in this strain and were not considered to be treatment-related.

Any other information on results incl. tables

Atmosphere analysis

Target concentration (mg/L)	1.0	3.75
Target concentration (ppm)	200	750
Mean achieved gravimetric concentration (mg/L)	0.75x10^-3	4.5x10^-3
Mean achieved gravimetric concentration (mg/L), standard deviation	0.2x10^-3	1.7x10^-3
Mean analysed concentration (mg/L)	1.05	3.61
Mean analysed concentration (mg/L), standard deviation	0.16	0.42

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LC50 value in this inhalation acute toxicity study was >3.61 mg/L.

Executive summary:

The acute inhalation toxicity of the test substance was investigated in a non-GLP study following to a large extent the OECD regulatory guideline. The experiment is considered relevant, adequate and conclusive.

Ten male and ten female rats (approximately 7 weeks old) were randomly assigned to two experimental groups, each comprising 5 males and 5 females. The animals were exposed nose-only to the target concentrations of 1.0 and 3.75 mg/L for a single period of 4 hours and then observed over a period of 14 days. The total particulate concentration of each test atmosphere was measured gravimetrically, but the particle size distribution of the aerosol was not measured because of the low particulate concentratios. The test atmospheres were analysed for the test substance using an adsorption tube containing CARBOTRAP (40-60 mesh) to initially trap the material. The test substance was then thermally desorbed from the tube into a gas chromatograph equipped with a flame-ionisation detector. The mean analysed concentrations were 1.05 mg/L (± 0.16 mg/L) and 3.61 mg/L (± 0.42 mg/L).

No deaths occured during the exposure period or the 14-day exposure period. A number of clinical signs were observed during exposure and on the first days after exposure. The animals had generally recovered by day 2 although abnormal respiratory noise persisted in males of both test groups up to day 5. There was an initial decrease in the bodyweight, buth the rate of bodyweight gain was similar to that seen in control rats of the same age and strain after day 3 post exposure. The only pathological finding was a slight decrease in liver weight and liver:bodyweight ratio in males exposed to 3.61 mg/L, when compared to control rats. Changes seen post mortem were part of the normal spectrum of background change in this strain and were not considered to be treatment-related.