Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP and no guideline was followed.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1987

Materials and methods

Test guideline
Guideline:
other: no data
Principles of method if other than guideline:
No specific test guideline was reported; however, a scientifically defensible approach was used to conduct the study.
Male rats were approximately 9-10 weeks old and weighed 325±16.8 g at study start. Food and water were provided ad libitum except during inhalation exposures.
Test atmospheres were generated by passing an airstream over the liquid test substance in a generating flask and then feeding the effluent vapor into the chamber air supply. Animal exposures were done in 1.0 m3 or 1.3 m3 dynamic exposure chambers. Chamber concentrations were measured periodically throughout the exposure and analyzed via an infrared gas analyzer.
All animals were observed daily and weighed monthly. All animals were allowed to die spontaneously or were sacrificed when moribund. Complete necropsies were performed at sacrifice. Nasal passages, brain, lung, trachea, larynx, liver, kidney, testes, and any other organs exhibiting gross pathology were examined microscopically.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dichloroacetyl chloride
- Physical state: liquid at room temp.
- Analytical purity: more than 95%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
9-10 week old male rats. The animals were quarantined for two weeks before the experiment.
TEST ANIMALS
- Source: Charles River breeding Laboratories, Wilmington, MA
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 325g+/-16.8g
- Acclimation period:2 weeks of quarantine, during this time complete serologic and pathologic analyses were done on randomly selected animals, these analyses were found to be negative.

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Remarks on MMAD:
MMAD / GSD: Exposure concentrations (mean +/-SD):
0.53+/-0.03
1.03+/-0.08
2.00+/-012
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic exposure chambers 1.0 and 1.3 m3, exposure was for 30 days (6 hours/dayx5 days/week)
- Method of holding animals in test chamber:
- Method of conditioning air:by varing the flow of air through the flasks, stable chamber concentrations were achieved
- System of generating particulates/aerosols: airstream passing over the liquid in a generating flask and then feeding the effluent vapor into the chamber air supply.
- Temperature, humidity, pressure in air chamber: room temperature

TEST ATMOSPHERE
- Brief description of analytical method used: infrared gas analyzer ( Wilkis Scientific Corp. South Norwalk, CT)

Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Chamber concentrations of chemicals were analyzed at half-hour intervals during the daily exposures by means of Wilkis Miran infrared gas analyzer with the use of appropriate wavelenght for the compound.
Duration of treatment / exposure:
30 days of exposure
Frequency of treatment:
6 h/d, 5 d/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.5, 1, 2 ppm
Basis:
no data
No. of animals per sex per dose:
50 animals / group
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: daily observation
BODY WEIGHT: monthly weight control


Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes , histologic sections were taken from each lobe of the lung, and from trachea, larynx, liver kidneys, testesand any other organs exhibiting gross pathology.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
effects observed, treatment-related
Details on results:
No mortality observed. At the highest dose group, after the appropriation 794 days, occurred in 2 animals nasal tumors (incidence: 4%), in the
Control group and the dose groups up to 1 ppm did not reveal any tumors.

Effect levels

Effect level:
2 ppm
Sex:
male
Basis for effect level:
other: no mortality observed

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The authors suggest that dichloroacetyl chloride, due to very rapid hydrolysis cannot target DNA of nasal mucosa cells.

Applicant's summary and conclusion

Conclusions:
No mortality observed at tested doses.
Executive summary:

In the study, at tested doses of 0.05, 1.00 and 2.00 ppm, no mortality was observed.