2,4-xylidine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-10-3 to 1988-07-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well performed GLP study according to previous OECD technical guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,4-xylidine

EC Number:

202-440-0

EC Name:

2,4-xylidine

Cas Number:

95-68-1

Molecular formula:

C8H11N

IUPAC Name:

2,4-dimethylaniline

Details on test material:

- Sample designation: 2,4-Xylidine
- Batch number: 048828-04
- The test substance was contained in three bottles, each containing approx. 1 litre
- One bottle contained a yellow liquid, two a pink liquid. IR spectra revealed no differences
- On the advice of the supplier the contents of the three bottles were mixed for use in this study

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK Ltd, Abbots Ripton Road, Wyton, Huntingdon, England
- Age at study initiation: 6-8 weeks
- Weight at study initiation: ca. 200g on day of exposure
- Housing: propylene cages (38cm x 56cm x 18cm) with detachable wire mesh tops and floors, in groups of five (same sex).
- Diet: free access to a measured excess amount of food (Labsure LAD 1)
- Water: free access to a measured excess amount of tap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Humidity (%): 41-51%
- Photoperiod (hrs dark / hrs light): 12/12hrs

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Depending on the concentrations tested a vapour generator (highest dose only) or an aerosol generator (all other doses tested)
- Exposure chamber volume: approx. 120 litres
- Method of holding animals in test chamber: chamber divided by meshpartitions to provide 10 separate animal compartments
- Source and rate of air: supply of clean and fresh air , 25 litres per minute
- Method of conditioning air: in-flow meter was used to monitor air flow throughout the exposure
- System of generating particulates/aerosols: via syringe connected to the generator
- Method of particle size determination: May multistage liquid impringer


TEST ATMOSPHERE
- Brief description of analytical method used: wet-type gasmeter and May liquid multistage impringer
- Samples taken from breathing zone: 5 or 6 samples were taken from the chamber during exposure
- There were no differences in temperature or relative humidity consiered likely to influence the results of the study

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: the results show that on average at least 84% of the test item present in the chamber atmosphere was in the form of vapour or droplets of respirable size, i.e. below 5.5µm aerodynamic diameter

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gas chromatography

Duration of exposure:

4 h

Concentrations:

0.620 (15% variation); 0.549 (10% variation); 1.530 (18% variation); 2.213 (23% variation); 1.695 (48% variation); 1.438 (38% variation) mg/L

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:weighing: daily, clinical observations: continuously during exposure, twice daily during observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights (lung), histopathology (lungs preserved for further histopathological examinations), Food and Water consumption

Statistics:

Calculation of LC50 according to the log probit method of Miller and Tainter

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.53 mg/L air

Exp. duration:

4 h

Remarks on result:

other: std. error. 0.205mg/L

Mortality:

table 1

Clinical signs:

other: - signs seen were as expected for inhalation of an irritant aerosol/vapour, hence including partial closing of the eyes, a reduced and irregular respiration rate and adoption of hunched body posture - at the higher concentrations a reduced motor activity

Body weight:

- all rats that died as a result of exposure lost weight until their death
- suriviving rats had moderate decrease in body weight and body weight gain up to three days following exposure
- water and food consumption were reduced

Gross pathology:

- rats that died as a result of exposure: congestion of lungs, bladder distension and liver pallor; findings probably due to the long period of unconciousness
- surviving rats: no treatment related effects

Other findings:

- the lung weight to body weight ratio was increased due to a high lung weight in some rats that died following exposure to the test item
- the lung weights were within normal limits for the control rats and those that survived exposure to the test item

Any other information on results incl. tables

Table 1: Mortality

Group	Deaths Male	Deaths Female	Deaths Total
Control	0/5	0/5	0/10
0.620 mg/L	0/5	0/5	0/10
0.549 mg/L	0/5	0/5	0/10
1.530 mg/L	1/5	0/5	1/10
2.213 mg/L	5/5	5/5	10/10
1.695 mg/L	5/5	5/5	10/10
1.438 mg/L	2/5	0/5	2/10

 

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

From the mortality data of the treated groups the LC50 (4-hour) for 2,4-Xylidine was established at 1.53 mg per litre of air. The standard error of the estimate was 0.205mg/L.
The substance has to be classified as T, R23; H 330 - Fatal if inhaled (Cat. 2).

Executive summary:

The substance has to be classified as T, R23; H 330 - Fatal if inhaled (Cat. 2).