Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study predates respective OECD guidelines and Good Laboratory Practices but was conducted according to regulations for the Enforcement of the Federal Hazardous Substances Act (USA). The main limitations of the study are the exposure duration which was restricted to one hour and the lack of determination of the actual exposure concentrations. There were no details on the exposure conditions and in particular on the particle-size distribution of the generated aerosol.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Revised, Federal Register, september 17, 1964
Principles of method if other than guideline:
Rats were exposed (whole-body) to the test substance suspended in distilled water for 1 hour at a concentration of 180 mg/l. Observations of the appearance and behaviour of the animals were made continuously during the exposure period, and at frequent intervals thereafter for a total of 14 days. At the end of the observation period the rats were weighed, sacrificed and gross necropsies were performed.
GLP compliance:
no
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
other: albino
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 227 -276 g
- Fasting period before study:
- Housing: by groups in wire mesh cages
- Diet: ad libitum (except during exposure)
- Water : ad libitum (except during exposure)

No other data available.

ENVIRONMENTAL CONDITIONS

No data available.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: water
Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: chamber consisted of a glass jar fitted with a plexiglass lid.
- Exposure chamber volume: 29 cm in diameter and 30 cm deep.
- Source and rate of air: The lid contained air intake and exit tubes positioned at the top and bottom of the chamber, respectively. air flow was 10 l/min.
- System of generating particulates/aerosols: The sample was introduced into the chamber atmosphere by using a Preval pack and a series of one or two second sprays approximately every 30 seconds.

No other data available.

TEST ATMOSPHERE
- No analytical measures were performed.
- Particle size distribution and Mass median aerodynamic diameter were not determined.

VEHICLE
- Composition of vehicle : water
- Concentration of test material in vehicle : A suspension of the test substance in distilled water was prepared by adding 1 part test substance to 29 parts water.

No other data available.


Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
60 min
Concentrations:
180 mg/l
No. of animals per sex per dose:
10 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: continuously during the exposure period, and at frequent intervals thereafter. Body weights were recorded prior to dosing and at the end of the observation period.
- Necropsy of survivors performed: yes.



Statistics:
None .

Results and discussion

Preliminary study:
Not performed.
Effect levels
Sex:
male
Dose descriptor:
LC50
Effect level:
> 180 mg/L air (nominal)
Exp. duration:
60 min
Mortality:
No mortalities occurred during the study.
Clinical signs:
other: - During the exposure period: the rats exhibited "excited" activity upon initiation. The majority of rats exhibited preening, excessive masticatory movements, excessive salivation stains, damp hair coats, lacrimation and serosanguinous stains around the n
Body weight:
The rats showed an average body weight gain of 26 g over the course of the study, which was considered to be normal for rats of this age strain and sex.
Gross pathology:
No abnormalities detected.

Applicant's summary and conclusion

Interpretation of results:
other: No indication of toxic potential by inhalation
Remarks:
Criteria used for interpretation of results: expert judgment
Conclusions:
The 1 hour LC50 was found to exceed 180 mg/l. No mortalities occurred and the symptomatology restricted to the day of exposure did not indicate a toxic potential by inhalation.
Executive summary:

The acute inhalation toxicity of the test item (DHTDMAC, 75% active in isopropanol/water) was assessed in male albino rats using a technique from the US Federal Hazardous Substances Regulations specified in the Revised, Federal Register, september 17, 1964. The study predates GLP requirements.

A group of ten rats were exposed whole-body to the test item in an inhalation chamber for 1 hour. The nominal concentration of the test item in the chamber atmosphere was calculated to be 180 mg/l of mist.

At the end of the exposure period, the animals were removed from the chamber. The animals were observed continuously for appearance and behavior during the exposure period and at regular intervals thereafter for a total of 14 days. Rats were subjected to gross necropsy at the end of the study.

No mortalities were recorded at any time. Clinical signs were only present on the day of exposure and included, excess salivation, serosanguineous stains around the nose, laboured respiration and damp/wet coats. For the remainder of the study, all rats exhibited normal behaviour and appearance. Necropsy revealed no significant gross pathological alterations.

The acute LC50 was determined to be greater than 180 mg/l after 1 hour exposure.