Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides, reaction products with polyethylenepolyamines and tall-oil fatty acids, humates hydrochlorides

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-08-29 to 2014-02-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

- Substance type: UVCB
- Physical state: powder

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 Limited, Margate, Kent, UK
- Age at study initiation: 7-8 weeks old
- Weight at study initiation: 319-326 g for males; 227-253 g for females
- Fasting period before study: Not reported
- Housing: 5 per cage by sex in suspended, polycarbonate/polypropylene cages with stainless steel grid tops and solid bottoms
- Diet (e.g., ad libitum): SDS Rat and Mouse (modified) No. 1 Diet SQC Expanded provided ad libitum
- Water (e.g., ad libitum): Municipal water provided ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Air changes (per hr): 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Modular snout only flow through system
- Exposure chamber volume: Not reported
- Method of holding animals in test chamber: Animals restrained in clear, tapered, polycarbonate tubes with an adjustable back-stop to prevent the animals from turning in the tubes
- Rate of air: 20 L/min
- Method of conditioning air: Not reported
- System of generating particulates/aerosols: Rotating brush generator
- Method of particle size determination: Particle size was measured by a cascade impactor located and sealed in a port in the animals’ breathing zone; particle size distribution was determined by plotting the cumulative percentage (by mass) of particles smaller than the cut point of each impactor stage against the logarithm of each stage cut point. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of the test aerosols were derived by Probit analysis.
- Treatment of exhaust air: Chamber air was exhausted via a double filter system with a fibre glass coarse prefilter and a HEPA ultimate particulate filter.
- Temperature, humidity, pressure in air chamber: 20.8 ± 0.62 ºC, 9.7 ± 1.06 %, pressure not reported

TEST ATMOSPHERE
- Brief description of analytical method used: The gravimetric exposure aerosol concentration was sampled 10 times during the exposure period from the animal's breathing zone. The test aerosols were sampled with filter media placed in a filter holder with a sampling system in place. Filters were weighed before and after sampling, and the volume of air sampled was recorded. Filter samples were collected at a target aerosol flow rate of 0.5 L/min.
- Samples taken from breathing zone: Yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Particle size distribution was measured at approximately 1 hr and again at 3 hr during the 4 hr exposure period with a cascade impactor.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD = 3.98-3.99 µm; GSD 2.482-2.392

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: A target dose of 2 mg/L was selected because it was the maximum feasible aerosol concentration at a MMAD minimally above the OECD recommended limit of 4 µm.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

2.17 mg/L

Remarks on duration:

4 hr

Concentrations:

2000 mg/m3

No. of animals per sex per dose:

5 animals/sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed prior to treatment, at the start of treatment, at 30 minute intervals until the end of treatment, 1 and 2 hour after treatment, and then daily. Body weights were recorded prior to treatment and on Days 1, 2, 3, 7, 10, and 14 after treatment.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs of toxicity, gross pathology

Statistics:

Not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2 170 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No adverse effects observed at the highest dose tested.

Mortality:

No mortality was observed throughout the study.

Clinical signs:

other: Two males exhibited shallow breathing 60-90 minutes into exposure; all animals exhibited labored breathing 120 minutes into exposure, which continued until the end of exposure. Additional clinical signs of toxicity included stained coat, head, forelimbs,

Body weight:

A minimal decrease in body weight was noted in 2/10 animals on Day 1; changes in weight were considered to be normal for strain and age.

Gross pathology:

No notable macroscopic findings observed in any animals except one male that exhibited dark and discolored lungs. Findings from this animal were considered to be of equivocal toxicological significance and due to the test item being black color.

Other findings:

No other notable findings reported.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No systemic toxicity was observed after rats were exposed to organolignite as an aerosol for 4 hrs at a concentration of 2170 mg/m3.

Executive summary:

In an acute inhalation toxicity study, groups of Sprague-Dawley rats (5/sex) were exposed (nose only) by inhalation route to organolignite for 4 hours at nominal concentrations of 2000 mg/m³ (Charles River Laboratories, 2014). A target dose of 2000 mg/m³ was selected because it was the maximum feasible aerosol concentration at a MMAD minimally above the OECD recommended limit of 4 µm. Particles for testing were reduced in size in accordance with OECD guidelines. Animals then were observed for 14 days.

No mortality was observed throughout the study. There were no treatment related clinical signs, necropsy findings or changes in body weight. There was a minimal decrease in body weight observed in 2 animals; however, this effect was considered to be normal for this strain and age. One male exhibited dark/discolored lungs, which was due to the color of the test material. The inhalation LC50 was determined to be > 2170 mg/m³ (equivalent to 2.17 mg/L) in males and females.