Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08th October 1986 - 22 October 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
yes
Remarks:
male animals slightly younger than specified in the protocol
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Test material: Product as manufactured in mineral oil solvent further diluted in mineral oil (65/35).
Details on test material:
Description : Brown liquid (Note: product as manufactured diluted in mineral oil [65/35])
Date Received: 3 October 1986
Label Information : The Lubrizol Corporation Wickliffe , Ohio
Experimental Product
Sample: OS #80020
Concentration: 35% active ingredient (contains 65% oil)
Caution: Avoid contact with eyes, skin, vapour.
Expiration Date : None
Analysis: The identity , strength, purity and composition; and synthesis, fabrication , and/or derivation of the test substance have been documented by the sponsor.
Stability: The stability of the test substance has been determined by the sponsor.
Storage : Temperature monitored room (60-85OF) .

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source:
Charles River Breeding Laboratories, Inc. Kingston, New York 12484

- Age at study initiation:
nine to twelve weeks old

- Weight at study initiation:
194g to 232g.

- Fasting period before study:
Not applicable

- Housing:
Animals were doubly-housed i n suspended stainless steel wire mesh cages during the first week of the acclimation period and individually during the remainder of the acclimation period and all other non-exposure periods

- Diet:
ad libitum

- Water:
ad libitum

- Acclimation period:
eight days

ENVIRONMENTAL CONDITIONS

- Temperature:
67-76°F

- Humidity:
30-70%

- Photoperiod (hrs dark / hrs light):
twelve hours continuous light and twelve hours darkness

IN-LIFE DATES:
From: 08 October 1986 To: 22 October 1986

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
Approximately 410 mls of test material was placed into a 500 ml Erlenmeyer flask and connected to an FMI fluid metering pump (Model #RPG-20) with a 1/4" piston, plus exposure chamber

- Exposure chamber volume:
approximately 100 litres

- Method of holding animals in test chamber:
Animals were i ndividual ly housed in a 100 liter Plexiglas exposure chamber.

- Source and rate of air:
House-supply air was delivered through 1/4" Tygonm tubing, a Nupro metering valve and a Union Carbide pressure gauge (at a constant backpressure of 25 pounds per square inch, psi) to a 0-20 lpm Dwyer flowmeter at a calibrated flow rate of 20.1 lpm into the air inlet of the atomizer to generate the aerosol.

- Method of conditioning air:
None described

- System of generating particulates:
Erlenmeyer flask and connected to an FMI fluid metering pump (Model #RPG-20) with a 1/4" piston

- Method of particle size determination:
Marple Personal Cascade Impactor (Westech IS Ltd, Beds., UK).

- Treatment of exhaust air:
None specified

- Temperature and humidity: An Airguide humidity indicator was used to continuously monitor relative humidity and a Taylor thermometer was used to continuously monitor air temperature in the exposure chamber. Recordings of temperature, relative humidity and air flow rate readings were made every 1/2 hour during exposure.

TEST ATMOSPHERE
- Brief description of analytical method used:
Samples for determination o f the exposure level were drawn from the exposure chamber using Whatman glass microfibre filter paper (Type GF/F, 3.7 cm) mounted in a Gelman gravimetric filter holder. Samples were withdrawn for 4 minutes at an airflow rate of 1 lpm, once per hour from the normal sampling portal and once during exposure from the distribution sampling portal.

- Samples taken from breathing zone:
Yes

VEHICLE
- Composition of vehicle (if applicable):
Not applicable

- Concentration of test material in vehicle:
Not applicable

- Justification of choice of vehicle:
Not applicable

- Lot/batch no. (if required):
Not applicable

- Purity: Not applicable

- MMAD (Mass median aerodynamic diameter:
9.93 µm

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Not applicable.
Analytical verification of test atmosphere concentrations:
no
Remarks:
Gravimetric only
Duration of exposure:
4 h
Concentrations:
Mean Maximum Attainable (mg/L) 1.9
Nomianl Concentration (mg/L) 41
Mean Mass Median Aerodynamic Diameter (µm) 4.2
Inhalable Fraction (% <10 µm) 93
Geometric Standard Deviation 1.9
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 and weighing: Day 1 (Day of Exposure) All animals were observed individually, immediately prior to exposure, as a group at approximately fifteen-mi nute intervals during the first hour of exposure and hourly for the remainder of the exposure period. All animals were observed individually upon removal from the chamber (half-hour after exposure was completed) and hourly for two hours post-exposure. Detailed physical observations were recorded at each interval. Days 2 through 15 (Post-exposure) Detailed observations were recorded for animals once daily; viability was assessed twice daily.
Individual bodyweights Day 1 (immediately prior to exposure) and on Days 2, 3, 5, 8 and 15 (just prior to sacrifice).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs.
Postmortem: A complete gross postmortem examination was performed on all animals sacrificed a t the end of the 14-day post-exposure observation period. The gross postmortemexaminations included examination of the nasal passages, trachea, external surface, allorifices, the cranial cavity , carcass, the brain and spinal cord, the thoracic, abdominal and pelvic cavities and their viscera, and the cervical tissues and organs.
Method of Sacrifice: Exsanguination while under ether anesthesia.
Statistics:
Data evaluations included the relationship, if any, between the animals’ exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, necropsy findings, bodyweight changes, mortality and any other toxicological effects. Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) of the test material was made.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.9 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: CL not given
Mortality:
All animals survived the duration o f the study
Clinical signs:
other: Observations noted during exposure included reduced activity, closed eyes and a few animals with labored breathing towards exposure completion. Signs exhibited by animals upon removal from the chamber and during the two-hour post-exposure observation peri
Body weight:
Test Week 1 body weights were slightly less than pretest values in some animals. This was considered a minimal response to exposure. Test Week 2
body weights were considered unremarkable.
Gross pathology:
No gross effects of the test material were observed.
Other findings:
Not applicable.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Ten of ten CD (Sprague-Dawley derived) rats receiving a single four-hour exposure to 1.9 mg/l o f OS 80020 (product as manufactured diulted to 65% in mineral oil) as a maximum attainable respirable aerosol, survived until sacrifice on Day 15. Signs of treatment included reduced activity and labored breathing during the exposure. Signs of treatment such as secretory signs and matted coats persisted during the first week after exposure, but generally abated before the Day 15 sacrifice. A minimal, transient adverse effect upon body weight was produced by treatment. Otherwise bodyweight values were considered unremarkable. Gross postmortem observations were considered unremarkable.
Executive summary:

Introduction

A single four-hour whole-body inhalation exposure was performed for Lubrizol Corporation using CD (Sprague-Dawley derived) rats (5/sex) todetermine the acute inhalation toxicity of OS 80020 (product as manufactured diluted to 65% in mineral oil). The test substance was administered into the breathing zone of the animals as an aerosol on 8 October 1986.

Species and strain of the test animal, method and route of test substance administration and target exposure level were determined by the sponsor. The test procedures followed guidelines described in the Health Effects Test Guidelines; Office of Pesticides and Toxic Substances, United States Environmental Protection Agency (EPA), October 1984 and in the Pesticide Assessment Guidelines, Subdivision F; Hazard Evaluation: Human and DomesticAnimals; Office of Pesticide Programs, United States Environmental Protection Agency, Office of Pesticide and Toxic Substances, November 1982; Section 81 -3 "Acute Inhalation Toxicity Study". This study was conducted at Bio/dynamics, Inc., Mettlers Road, East Millstone, New Jersey 08873.

Methods

A group of ten CD (Sprague-Dawley Derived) train rats (five males and five females) was exposed to an aerosol. The animals were exposed for four hours using a whole body exposure system, followed by a fourteen day observation period.

ResultsThe mean achieved atmosphere concentration was as follows:

Atmosphere Concentration

Mean Maximum Attainable (mg/L)

Nominal (mg/L)

1.9

41

The characteristics of the achieved atmosphere were as follows:

Mean Maximum Attainable Atmosphere Concentration (mg/L)

Mean Mass Median Aerodynamic Diameter (µm)

Inhalable Fraction

(% <10 µm)

Geometric Standard Deviation

1.9

4.2

93

1.9

The mortality data were summarised as follows:

Mean Maximum Attainable Atmosphere Concentration (mg/L)

Deaths

Male

Female

Total

1.9

0/5

0/5

0/10

Clinical Observations

Observations noted during exposure included reduced activity, closed eyes and a few animals with labored breathing towards exposure completion. Signs exhibited by animals upon removal from the chamber and during the two-hour post-exposure observation period on Day 1 included secretory signs, some respiratory signs, hunched appearance and matted coats. During Test Week 1, test animals exhibited decreasing signs of treatment such as secretory signs and matted coat. These signs mostly abated by Day 8 and during Test Week 2 animals exhibited few continuing signs of treatment.

Bodyweight

Test Week 1 body weights were slightly less than pretest values in some animals. This was considered a minimal response to exposure. Test Week 2 body weights were considered unremarkable.

Necropsy

No gross effects of the test material were observed.

Conclusion Ten of ten CD (Sprague-Dawley derived) r a t s receiving a single four-hour exposure to 1.9 mg/l of OS 80020 as a maximum attainable respirable aerosol, survived until sacrifice on Day 15. Signs of treatment included reduced activity and labored breathing during the exposure. Signs of treatment such as secretory signs and matted coats persisted during the first week after exposure, but generally abated before the Day 15 sacrifice. A minimal, transient adverse effect upon body weight was produced by treatment. Otherwise bodyweight values were considered unremarkable. Gross post mortem observations were considered unremarkable.