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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3,4-Dichloroanilin rein
- Physical state: solid, brown
- Analytical purity: 99.2 %
- Lot/batch No.: 243
- Stability under test conditions: yes
- Storage condition of test material: +6°C, in the dark

1 mg/ cubic meter = 0.15 mL/cubic meter (ppm)
1 mL/ cubic meter (ppm)= 6.63 mg / cubic meter

Test animals

Species:
rat
Strain:
other: Bor: WiSW (SPF-Cpb)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 2 to 3 months
- Weight at study initiation: 170 to 200 g
- Housing: 5 animals of one sex per Macrolon type III cage
- Diet: ad libitum, Altromin 1324
- Water: ad libitum, tap water
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
other: polyethylene glycol: ethanol = 1:1
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: purchased at Rhema Labortechnik, Hofheim, Germany
- Exposure chamber volume: 7 L
- Method of holding animals in test chamber: animals were put in a exposition tube, tail was left outside
- Source and rate of air: 70 % of the dynamic air flow of incoming air were filtered before exit, air flow towards rats, 86 air changes per hour
- Method of conditioning air: kompressor, cleaned from dust, water and oil,
- System of generating particulates/aerosols: 100µL / min were sprayed into a pre-seperator and nebulized before entering the chamber
- Method of particle size determination: Aerodynamic particle sizer Laser-Velocimeter TSI-APS 3300
- Treatment of exhaust air: was cleaned through a filter system
- Temperature, humidity, pressure in air chamber: 23.5 °C, 34% humidity,


TEST ATMOSPHERE
- Brief description of analytical method used: GC with FID
- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable): Polyethylene glycol E400
- Concentration of test material in vehicle (if applicable):
- Justification of choice of vehicle:
- Lot/batch no. (if required):
- Purity:


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
324 mg/m³: 99 % < 5 µm 1828166 particles per ccm
631 mg/m³: 96 % < 5 µm 933674 particles per ccm
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
324 mg/m³: 1.89 µm / 1.52
631 mg/m³: 2.25 µm/ 1.58


Analytical verification of test atmosphere concentrations:
yes
Remarks:
Aerosolphotometer RAS-2
Duration of exposure:
4 h
Concentrations:
0, 324 or 631 mg/cubic meter ( higher concentration technical not possible)
No. of animals per sex per dose:
5 per sex and dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: repeated observations on the day of application, twice a day from there on, weighing: d0, d3, d7, d14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
Chi-square-test, Fisher-test, for clinical signs; F-Test for body weight gain

Results and discussion

Effect levels
Dose descriptor:
LC50
Effect level:
> 0.631 mg/L air
Exp. duration:
4 h
Mortality:
no mortality observed
Clinical signs:
Only the high dose group showed sings of toxicity on the day of application indicated by bradypnoe and reduced motility and recovered thereafter.
Body weight:
no overall influence on weight gain. Both sexes of the high dose group showed reduced weight gain between day 0 and day 3 post application.
Gross pathology:
no findings

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Like other chloroanilines, the primary toxic effect of 3,4-dichloroaniline is methaemoglobin formation. Taking into account that humans are much more sensitive to methaemoglobin producing substances than rats and that sufficient results of studies with cats, better suited to judge the level of toxicity for humans, are not available, 3,4-dichloroaniline is classified as Toxicity Category III.
Executive summary:

Maertins, T, 1990

The inhalative acute exposure of rats according to OECD 403 with 324 or 631 mg 3,4-dichloroaniline / m³ for 4 h was not fatal for rats. Testing of higher concentrations was technical not possible. Only the high dose group showed signs of toxicity indicated by bradypnoe and reduced motility on the day of exposure but recovered thereafter.