Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: basic information given, scientifically acceptable

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
GLP compliance:
yes
Remarks:
testing lab.
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
99.5% active ingredient

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Prior the initiation of exposure to the test substance, animals were arbitrarily selected from the Bio/dynamics' in-house population based on acceptablephysical examinations and body weights.
The rats were identified after select with a metal ear tag bearing its unit animal number.
They were doubly-housed in stainless steel, wire mesh cages during the first week of the acclimation period and individually-housed during the remainder of the acclimation period and all other non-exposure periods.
Food and water were available ad libitum.
Temperature: Specified range: 67-76°F; monitored and recorded twice daily; maintained within this range to the maximum extent possible.
Relative humidity: Specified range: 30-70%; monitored and recorded twice daily; maintained within this range to the maximum extent possible.
Environmental conditions : 12 hour light/dark cycle via automatic timer.

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: clean air
Details on inhalation exposure:
Impinger samples of chamber air were taken every hour for one minute and analyzed colorimetrically. Although the chamber concentrations did not remain constant over the exposure duration, there was no definitive relationship between time and concentration.
Duration of exposure:
4 h
Concentrations:
5.2, 17, 28, 60 ppm
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
Duration of observation period following administration: 14 days
All animals were observed individually, immediately prior to exposure, as a group at approximately fifteen-minute intervals during the first hour of exposure and hourly for the remainder of the exposure period. All survivors were observed individually upon removal from the chamber (half-hour after exposure was completed) and hourly for two hours postexposure. Detailed physical observations were recorded at each interval.
Neurological examination was performed prior to exposure and at 1 and 4 hours post-exposure.
Statistics:
A calculation of median lethal concentration and 95% confidence limits was performed according to the method of Litchfield and Wilcoxon.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.08 mg/L air
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
10 ppm
Exp. duration:
4 h
Remarks on result:
other: original value
Mortality:
7.5 ppm: 0/10, 24 ppm: 10/10; 38 ppm: 10/10; 80 ppm: 10/10; control: 0/10
Clinical signs:
During the test substance exposures, the most commonly noted signs of toxicity were labored breathing, eyes closed, reduced activity. The control animals were unremarkable. Treatment-related signs were seen among the test substance-exposed animals especially at the 3 higher levels. These signs included labored breathing, rales, lacrimation and nasal discharge. Following the 60 ppm exposure, many of the animals were noted as cool to the touch. The control and 5.2 ppm animals showed minimal responses during this interval. Following the 3 higher exposure levels, signs similar to those seen immediately after exposure progressed and lead to complete mortality. Following 5.2 ppm exposure, a recovery was generally seen within a few days after exposure. The control animals showed the usual incidence of signs throughout the entire observation period.
Body weight:
Significant weight losses were observed following the test substance exposures. Animals in the 3 high exposure groups continued to lose weight until their death. The 5.2 ppm animals showed recovery within a few days after exposure.
Gross pathology:
Various observations of discolored tissues and edema of the lungs were noted in spontaneously dying animals. These signs are not uncommon in animals which died prior to exsanguination. Red lungs and turbinates were also noted among the animals that were sacrificed. The relation to treatment of these findings is equivocal on the basis of gross examination only.
Other findings:
Neurologic examination: A treatment-related pattern was seen during the first 2 days after exposure at the 3 high levels. The most common finding was flaccidity of body tone on the day after exposure. The 60 ppm animals also showed flaccidity of limb tone, decreased to pinch, righting and startle reflex, and ataxia. The control and 5.2 ppm animals were comparable.

Any other information on results incl. tables

The investigators calculated a 4-hr LC50 of 10 ppm (both sexes combined, 95% confidence interval of 8.5-13 ppm).

No deaths occurred at 5.2 ppm but 100% mortality was observed for the remaining exposure groups. Deaths occurred at 1 to 8 days post exposure. For the 60, 28, 17, and 5.2 ppm groups, the respective mortality ratios at postexposure Day 5 were 6/10, 7/10, 9/10 and 0/10.

Carboxyhemoglobin increased in a dose-related fashion (up to 11.6% increase in the high-dose group relative to controls) but was unaffected in the low-dose group. A lethality vs concentration plot provided in the study indicated that the 5.2 ppm concentration was near a lethality threshold.

Gross pathology of rats that died spontaneously revealed red discoloration in several tissues(not specified) and pulmonary edema.

Applicant's summary and conclusion