Reactionmass of dodecan-2-yl prop-2-enoate and dodecan-3-yl prop-2-enoate and dodecan-4-yl prop-2-enoate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes

Test type:

fixed concentration procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reactionmass of dodecan-2-yl prop-2-enoate and dodecan-3-yl prop-2-enoate and dodecan-4-yl prop-2-enoate

EC Number:

947-818-2

Cas Number:

1612783-92-2

Molecular formula:

C15H28O2

IUPAC Name:

Reactionmass of dodecan-2-yl prop-2-enoate and dodecan-3-yl prop-2-enoate and dodecan-4-yl prop-2-enoate

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 3M Company, Batch 6
- Expiration date of the lot/batch: 04 October, 2019
- Purity test date: 04 October, 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Kept in a controlled temperature area set to maintain 18-24 C
- Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material)

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable)

OTHER SPECIFICS:

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Approximately 9 weeks
- Weight at study initiation: Males: 304-315 g, Females: 208-214 g
- Fasting period before study: None
- Housing: Upon arrival, all animals were housed individually in suspended wire-mesh cages. Caging was cleaned at appropriate intervals. The animals were maintained in accordance with SOPs and the Guide for the Care and Use of Laboratory Animals (National Research Council, 2011). On the day of exposure, the animals were placed in nose-only exposure holding tubes in the animal room, transported to the exposure room, exposed for the requisite duration, and then returned to their home cages.
- Diet (e.g. ad libitum): The basal diet used in this study, PMI Nutrition International, LLC, Certified Rodent LabDiet® 5002 (block), is a certified feed with appropriate analyses performed by the manufacturer and provided to Charles River Ashland.
- Water (e.g. ad libitum): Reverse osmosis-treated water supplyingthe facility is analyzed for contaminants according to SOPs. Filters servicing the automatic
watering system are changed regularly according to SOPs. The results of the diet and water analyses are retained with the Charles River facility data. No contaminants were present in animal feed or water at concentrations sufficient to interfere with the objectives of this study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26 C
- Humidity (%): 30-70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 July, 2018 To: 13 August, 2018

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

ca. 2.3 µm

Geometric standard deviation (GSD):

ca. 2.02

Remark on MMAD/GSD:

Two aerosol particle size measurements were conducted during the exposure using a 7-stage cascade impactor (Model No. 02-100-2L-A, In-Tox Products; Moriarty, NM). Pre-weighed, 22-mm stainless steel discs were used for the collection substrates for Stage 1 through Stage 7. A 25-mm glass-fiber filter (Type A/E, PALL Corporation) was used as the collection substrate for the final stage. The sample flow rate was measured using a mini-BUCK calibrator (Model No. M-5, A.P. Buck Inc.; Orlando, FL). Samples were collected at approximately 2 LPM for 0.25 minutes. The filters were re-weighed and the particle size was calculated based on the impactor stage cut-offs. The aerosol size was expressed as the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD).

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:A liquid droplet aerosol atmosphere of the test substance was generated using a 3-jet Collision nebulizer(BGI, Inc.; Waltham, MA) filled with an appropriate amount of test substance. Additional test substance was delivered to the nebulizer using a syringe pump (Model No. 975, Harvard
Apparatus; Holliston, MA) and a 100-mL glass syringe. Using a regulator (Model No. 8802K, Coilhose Pneumatics Inc.; East Brunswick, NJ), dry, breathing quality, in-house, compressed air at a controlled pressure was supplied to the air port of the nebulizer to effect atomization of the test substance. The aerosol was delivered to the nose-only exposure system through 1/2-inch respiratory tubing to the nose-only exposure system. A “T”-fitting was placed between the nebulizer and the exposure system, and humidified supply air was added using a rotameter-type flowmeter (Model No. 127M, Barnant Co./Gilmont Instruments; Barrington, IL). Exhaust atmosphere was filtered using a Solberg filter (Model No. CSL-850-200HC, Solberg Manufacturing, Inc.; Itasca, IL) prior to entering the facility exhaust system, which consists of redundant exhaust blowers preceded by activated-charcoal and HEPA-filtration units. Negative
pressure within the exposure system was checked at a “T”-fitting in-line prior to the facility exhaust system.
- Exposure chamber volume: 7.9 L
- Method of holding animals in test chamber: Animal holding tubes
- Source and rate of air: Airflow to the exposure system was provided using a dry, breathing quality, in-house, compressed air source and an in-house supply air source utilizing HEPA-filtration and activated charcoal to pre-treat room air. 13-17.5 liters per minute (LPM)
- Method of conditioning air: “T”-fitting was placed between the nebulizer and the exposure system, and humidified supply air was added using a rotameter-type flowmeter (Model No. 127M, Barnant Co./Gilmont Instruments; Barrington, IL).
- System of generating particulates/aerosols: A liquid droplet aerosol atmosphere of the test substance was generated using a 3-jet Collision nebulizer(BGI, Inc.; Waltham, MA) filled with an appropriate amount of test substance. Additional test substance was delivered to the nebulizer using a syringe pump (Model No. 975, Harvard Apparatus; Holliston, MA) and a 100-mL glass syringe. Using a regulator (Model No. 8802K, Coilhose Pneumatics Inc.; East Brunswick, NJ), dry, breathing quality, in-house, compressed air at a controlled pressure was supplied to the air port of the nebulizer to effect atomization of the test substance. The aerosol was delivered to the nose-only exposure system through 1/2-inch respiratory tubing to the nose-only exposure system.
- Method of particle size determination: Two aerosol particle size measurements were conducted during the exposure using a 7-stage cascade impactor (Model No. 02-100-2L-A, In-Tox Products; Moriarty, NM). Pre-weighed, 22-mm stainless steel discs were used for the collection substrates for Stage 1 through Stage 7. A 25-mm glass-fiber filter (Type A/E, PALL Corporation) was used as the collection substrate for the final stage. The sample flow rate was measured using a mini-BUCK calibrator (Model No. M-5, A.P. Buck Inc.; Orlando, FL). Samples were collected at approximately 2 LPM for 0.25 minutes. The filters were re-weighed and the particle size was calculated based on the impactor stage cut-offs. The aerosol size was expressed as the Mass Median Aerodynamic Diameter (MMAD) and the Geometric Standard Deviation (GSD).
- Treatment of exhaust air: Exhaust atmosphere was filtered using a Solberg filter (Model No. CSL-850-200HC, Solberg Manufacturing, Inc.; Itasca, IL) prior to entering the facility exhaust system, which consists of redundant exhaust blowers preceded by activated-charcoal and HEPA-filtration units.
- Temperature, humidity, pressure in air chamber:

TEST ATMOSPHERE
- Brief description of analytical method used: Actual exposure concentrations were determined every 5 to 60 minutes using standard gravimetric methods. Samples were collected on pre-weighed, 25-mm glass-fiber filters (Type A/E, PALL Corporation; Ann Arbor, MI) held in an open-faced filter holder positioned in the animal exposure port (i.e., in the breathing zone of the animal) of the nose-only exposure system. A measured volume of the exposure atmosphere was pulled through the filter to quantitatively collect aerosol particles. The sample flow rate was measured using a mini-BUCK calibrator (Model No. M-5, A.P. Buck Inc.; Orlando, FL). Samples were collected at approximately 1 LPM for 0.5 minutes. Following sample collection, the filters were re-weighed and the concentration calculated as the filter weight difference divided by the sample volume.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Mean MMAD = 2.3 uM, GSD = 2.02 uM

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

ca. 4 h

Concentrations:

5.4 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 and weighing: All animals were observed for mortality, abnormalities, and signs of pain and distress twice daily for 14 days (once in the morning and once in the afternoon, except on the day of scheduled necropsy). All animals were observed once during the exposure, where only clinical signs visible in nose-only exposure restraint tubes were recorded. All animals were observed for clinical signs of toxicity after the 4-hour exposure when removed from exposure system, once 1 to 2 hours post-exposure, and once daily for 14 days following exposure. Observations were recorded and
included, but were not limited to: changes in the skin and fur, eyes and mucous membranes and also changes to the respiratory, circulatory, autonomic, and central nervous systems, somatomotor activity, and behavior pattern. Body weights were obtained prior to exposure on Day 0, and on Day 1, Day 3, Day 7, and
Day 14. A final body weight was collected for the animal that died on study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.4 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

1/5 females was found dead on Day 9. All other females survived through the end of the study period. No mortality was observed in the males.

Clinical signs:

other: No treatment-related clinical signs were observed during the study.

Body weight:

All animals lost 8 to 24 grams from Day 0 to Day 1. Two males and 3 females lost 2 to 44 grams from Day 3 to Day 7. One female was 33 grams less than the initial (Day 0) body weight by Day 14. All other surviving animals surpassed their initial body weight by Day 14.

Gross pathology:

There were no macroscopic findings noted for the animal that died. At the scheduled necropsy, macroscopic findings noted consisted of lungs that were not fully collapsed for 1 male and 1 female and clear fluid in the uterus for 1 female. There were no other macroscopic findings for animals at the scheduled necropsy.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Based on the results of the study, the LC50 of the test article is greater than 5.4 mg/L (aerosol).

Executive summary:

The acute inhalation lethality potential of the test article was evaluated in male and female Sprague Dawley rats. The study was conducted according to OECD 403 (2009) in compliance with OECD GLP regulations. Rats (5/sex) were nose-only exposed 5.4 mg/L of an aerosol of the test article for 4 -hours. Mortality, clinical observations, body weights, and body weight changes were evaluated over a 14-day post-exposure observation period. Necropsies were conducted on all animals. Total mortality was 1/10 animals (1 female mortality) with all animals losing weight from Day 0 to Day1. Two males and 3 females lost 2 to 44 grams from Day 3 to Day 7. One female was 33 grams less than the initial (Day 0) body weight by Day 14. All other surviving animals surpassed their initial body weight by Day 14. No other clinical signs of toxicity were observed. Based on the results of the study, the LC50 of the test article is greater than 5.4 mg/L (aerosol).