Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978-04-04 to 1978-07-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
1 hour exposure instead of 4 hours
GLP compliance:
not specified
Test type:
traditional method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of the test material: SN-1-4462-71X
- Chemical name: cumyl peroxyneodecanoate
- Purity: 75.5% (0.19% Hydro, 896 ppm Cl)
- Appearance: pale yellow liquid

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS & ENVIRONMENTAL CONDITIONS
- Source: no data
- Females (if applicable) nulliparous and non-pregnant: no data
- Age at study initiation: no data
- Weight at study initiation: 235-242 g (male rats), 200-214 g (female rats)
- Fasting period before study: no data
- Housing: The rats were housed individually in wire-mesh cages and were kept throughout the pre- and post-exposure periods in a temperature and humidity controlled room in accordance with standards outlined in the "Guide For the Care and Use of Laboratory Animals; DHEW No. (N.I.H. 74-23) 1974". During exposure, the rats were caged individually in compartmented wire-mesh exposure cages. The cages were placed in a 160-liter cubical, stainless steel and glass chamber. A constant chamber airflow was maintained by means of a rotary centrifugal air pump located at the exhaust side of the chamber. The chamber exhaust was filtered with an activated charcoal filter and a Cambridge Absolute® filter before being discharged outside of the laboratory.
- Diet (e.g. ad libitum): Purina Laboratory chow, ad libitum (except in the exposure chamber)
- Water (e.g. ad libitum): ad libitum (except in the exposure chamber)
- Acclimation period: 1 week

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
The vapors of the compound were generated by metering the liquid at the rate of 0.494 mL/min with a Harvard Infusion pump into a positive pressure atomizer located near the chamber air inlet at the top of the exposure chamber. An air pressure of 10 psig, with an air-flow rate of 8 L/min, was applied to the atomizer which aerosolized the liquid for rapid vaporization. The vapors and aerosols emerging from the atomizer were diluted by the incoming chamber air at the rate of 14 L/min to the desired concentration. The "metered" concentration of the compound (20.4 mg/L) in the chamber atmosphere was calculated from the ratio of the rate of liquid dissemination (449.5 mg/min*) to the rate of total chamber airflow (22 L/min). The total chamber airflow represents the volume of air ejected from the atomizer plus the volume of make-up air passing through the chamber per unit time.

*The specific gravity of the liquid was gravimetrically determined to be 0.91

Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
1 h
Concentrations:
20.4 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Observations for toxic signs and mortility were made during and immediately following the 1 hour exposure period and twice daily thereafter for 14 days.
- Frequency of weighing: Individual body weights were recorded prior to the 1 hour exposure and periodically thereafter.
- Necropsy of survivors performed: yes
Statistics:
no data

Results and discussion

Preliminary study:
n.a.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 20.4 mg/L air
Based on:
test mat.
Exp. duration:
1 h
Mortality:
None of the rats died in the experiment.
Clinical signs:
The immediate response of the rats to the experimental atmosphere was an increase of activity in preening. After several minutes of exposure, this activity decreased. After 20 minutes of exposure 50% of the rats exhibited slight dyspnea. At 30 minutes, all the rats exhibited slight dyspnea which persisted for the remainder of the exposure period. In addition, a few rats intermittently exhibited salivation. Slight dyspnea was observed in a few rats for 1 to 8 days post-exposure. In addition, one rat exhibited eye squint on day 1 post-exposure.
Body weight:
A slight body weight loss was observed in the rats for 1-5 day post-exposure. By the end of the 14-day post-exposure, the body weights of all the rats exceeded those of the pre-exposure values. See Table 1 in box 'Any other information on results incl. tables'.
Gross pathology:
Gross pathological examination of the rats which were sacrificed at the end of the experimental period revealed gray patches on the lungs of 1 male rat and no compound related pathologic changes in the remaining 9 rats.

Any other information on results incl. tables

Table 1: Individual Body Weights

Individual body weights (in grams)
Pre-exposure Post-exposure (Days)
0 1 3 5 7 14
Rat no. Sex
1 M 235 220 232 262 286 346
2 M 240 225 240 260 285 328
3 M 238 224 236 258 276 320
4 M 235 221 238 258 271 300
5 M 242 224 236 255 272 295
6 F 200 192 200 211 218 236
7 F 200 202 205 212 226 228
8 F 210 192 222 211 224 240
9 F 214 200 210 220 229 250
10 F 210 199 200 207 224 232

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute inhalation study, Charles River CD rats were inhaled via whole-body exposure to 20.4 mg/L for 1 hour. No mortality occurred during the 14-day observation period. Based on the results, the LC50 is considered to be greater than 20.4 mg/L.
Executive summary:

In an acute inhalation toxicity study conducted similar to OECD 403, groups of Charles River CD rats (5/sex) were exposed by inhalation route to LUPERSOL 188M75 containing 75.5% cumyl peroxyneodecanoate (0.19% Hydro; 896 ppm Cl-) for 1 hour to whole body at a concentration of 20.4 mg/L. Animals then were observed for 14 days. No mortality occurred. During exposure, animals showed an increase of activity in preen in and all rats exhibited slight dyspnea and some rats exhibited salivation. One rat exhibited eye squint on day 1 post-exposure. A slight body weight loss was observed in the rats for day 1 to 5 post-exposure. In one male rat, grey patches on the lungs were observed. Based on the results, the LC50 is greater than 20.4 mg/L.