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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:
key study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The restrictions being that there was no report of whether the study was in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: Charles River Breeding Laboratories, Inc., Kingston, NY

- Age at study initiation: 53 -56 days

- Housing: Two or three animals per cage were housed in in 23.5x20x18cm high stainless steel wire mesh cages on carriers .

- Diet: Pelleted feed (Certified Rodent Chow 5002, Relaton Purina Co., St. Louis, MO) was available ad libitum except during the exposure.

- Water: ad libitum, except during the exposure.




ENVIRONMENTAL CONDITIONS

- Temperature (°F): 66-76

- Humidity (%): 31-52

- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: none
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

- Exposure apparatus: A piston pump (Fluid Metering Inc., Oyster Bay, NY)

- Exposure chamber volume: ca. 1330 litres

- Method of holding animals in test chamber: The animals were in wire mesh cages inside the test chamber.

- Source and rate of air: No information available

- Temperature, humidity, pressure in air chamber: The temperature and relative humidity in the animal housing rooms were recorded continuosly with a seven day recording hygrothermograph (Cole Parmer Instruments, Chicago, IL). During the exposure the temperature was monitored with an airguide Humidity Indicator (Airguide Instrument Co., Chicago, IL).


TEST ATMOSPHERE

- Brief description of analytical method used: A Perkin-Elmer Model 3920B gas chromatograph equipped with a flame ionization detector was used to monitor the A-171 vapor concentrations in the chambres. A Spectra-Physics Series 4000 central processor, a data interface, and a Perkin-Elmer automatic gas sampling system (station and valve programmer units and a gas sampling valve) were used for the analyses.

- Samples taken from breathing zone: Yes

- The test material originated from a heated evaporator similar in design to that described by Carpenter et al., 1975


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
1981, 2335, 2798, 3547, and 5372 ppm (analytical). (Target concentrations of 2000, 2400, 2750, 3500 and 5000 ppm)
No. of animals per sex per dose:
5/sex (50 total)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were weighed prior to exposure and on post-exposure days seven and fourteen.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The animals were sacrificed following methoxyflurane anesthesis. The rats were exsanguited by severing the brachial blood vessels and a complete necropsy was performed. Any abnormal tissues were placed in a fixative and saved for possible future histologic examination.
Statistics:
The mean and standard deviations of the body weights, body weight changes and exposure concentrations were calculated. No statistical comparisons were made. The LC50 was determined by the moving averages method of Thompson's (1947) using the 3547, 2798 and 2335 ppm exposure groups.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
2 773 ppm
Exp. duration:
4 h
Mortality:
Mortalities occured at the 5372, 3547 and 2798 ppm concentrations in both male and female animals (summarised in table 1).
Clinical signs:
other: Clinical signs included perinasal, encrustation, unkempt fur, hypoactivity, blepharospasm, lacrimation, respiratory difficulties (mouth breathing, audible respiration, decreased respiration rate), ataxia, prostration, tremors, distended stomachs, a negati
Body weight:
Depressed mean body weight gains were observed for both sexes of the 1981 and 2335 ppm groups and males of the 2798 ppm group during the first week of the post exposure period, when compared to mean body weight gains observed during the second postexposure week.
Gross pathology:
Two males and four females of the 5372 exposure group had eye opacities with three males and five females also having gas-filled stomachs. There were no other gross lesions in any of the other exposure groups.
Other findings:
No other findings reported.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In a guideline study that was not conducted to GLP, an acute inhalation LC50 value of 2773 ppm (16.8 mg/l) was determined for rats.