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

Endpoint summary

Description of key information

OECD (420, 402, and 403) compliant studies were identified for organolignite and resulted in the following LD50s.

• The oral LD50 in female rats was > 2000 mg/kg.

• The dermal LD50 in male and female rats was > 2000 mg/kg.

• The inhalation LC50 in male and female rats was > 2170 mg/m3.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-07-16 to 2013-08-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

other: CD [Crl:CD(SD)]

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, Michigan
- Age at study initiation: Approximately 7 weeks
- Weight at study initiation: 177-199 g
- Fasting period before study: Animals fasted overnight prior to dosing (up to 16 hr)
- Housing: Housed 2-3 per cage to allow for co-mingling in solid bottom cages
- Diet (e.g., ad libitum): Block Lab Diet Certified Rodent Diet #5002, PMI Nutrition International, Inc. available ad libitum
- Water (e.g., ad libitum): Tap water available ad libitum
- Acclimation period: 7 to 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ~ 20 to 26°C (68 to 79°F)
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 400 mg/mL
- Lot/batch no. (if required): 2CA0440

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 females total

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Prior to randomization (Day -1) and on Days 1, 7, and 14
- Necropsy of survivors performed: Yes
- Other examinations performed: Gross macroscopic examination conducted after necropsy

Statistics:

Not applicable

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

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

Mortality:

No mortalities were observed.

Clinical signs:

other: No treatment-related clinical signs of toxicity were observed.

Gross pathology:

No treatment-related macroscopic changes were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

An oral LD50 of > 2000 mg/kg was established in female rats based on a lack of mortality.

Executive summary:

In an acute oral toxicity study, five fasted, female CD [Crl:CD(SD)] rats were given a single oral dose of organolignite in corn oil at a dose of 2000 mg/kg and observed for 14 days. There were no treatment related clinical signs, necropsy findings or changes in bodyweight. The oral LD50 was determined to be > 2000 mg/kg in females.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The quality of the whole database is high and meets the tonnage driven data requirements of REACH.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Limit test:

yes

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

2 170 mg/m³ air

Quality of whole database:

The quality of the whole database is high and meets the tonnage driven data requirements of REACH.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-07-09 to 2013-08-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products, Inc., Greenfield, Indiana
- Age at study initiation: Approximately 5-6 ½ months
- Weight at study initiation: 2.92 to 3.19 kg males; 2.90 to 3.08 kg females
- Housing: Individually housed in suspended, stainless steel, slatted floor cages
- Diet (e.g., ad libitum): Lab Diet® Certified Rabbit Diet #5322 limited upon arrival and increased in 25 g increments during the acclimation period until feeding was 125 g per day
- Water (e.g., ad libitum): Tap water available ad libitum
- Acclimation period: Approximately 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ~ 16 to 22°C (61 to 72°F)
- Humidity (%): 30 to 70%
- Photoperiod (hrs dark / hrs light): 12 hr dark/12 hr light

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area
- % coverage: 10%
- Type of wrap if used: gauze dressing secured with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes
- Time after start of exposure: 24-25 hr after exposure

TEST MATERIAL
- For solids, paste formed: yes/no

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of exposure:

24-25 hr

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males and 5 females

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for morbidity, mortality, injury, and food and water availability were conducted twice daily for all animals. Animals were observed on Day 1 at approximately 30 minutes, and 1, 2, and 4 hours after application for clinical signs of toxicity. Animals were then observed once a day thereafter until Day 14. Body weights were measured prior to randomization and on Days 1, 7, and 14.
- Necropsy of survivors was performed on Day 15

Statistics:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

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

Mortality:

No mortality was observed.

Clinical signs:

other: No adverse clinical signs of toxicity were observed.

Gross pathology:

There were no treatment-related macroscopic observations in either males or females.

Other findings:

No other treatment-related findings reported.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 in rats was > 2000 mg/kg.

Executive summary:

In an acute dermal toxicity study, groups of New Zealand White Hra:(NZW)SPF rabbits (5/sex) were dermally exposed to organolignite moistened in water for 24 hours to 10% of the dorsal body surface area at doses of 2000 mg/kg bw. Animals then were observed for 14 days.

 

There were no treatment related clinical signs, necropsy findings or changes in body weight. The dermal LD50 was determined to be > 2000 mg/kg in male and female rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The quality of the whole database is high and meets the tonnage driven data requirements of REACH.

Additional information

Organolignite did not show any acute toxicity when administered orally, dermally, and via inhalation. In an acute oral toxicity study, five fasted, female CD [Crl:CD(SD)] rats were given a single oral dose of organolignite in corn oil at a dose of 2000 mg/kg and observed for 14 days. There were no treatment related clinical signs, necropsy findings or changes in body weight. The oral LD50 was determined to be > 2000 mg/kg in females.

In an acute dermal toxicity study, groups of New Zealand White Hra:(NZW)SPF rabbits (5/sex) were dermally exposed to organolignite moistened in water for 24 hours to 15% of the dorsal body surface area at doses of 2000 mg/kg bw. Animals were then observed for 14 days. There were no treatment related clinical signs, necropsy findings or changes in body weight. The dermal LD50 was determined to be > 2000 mg/kg in male and female rabbits.

In an acute inhalation toxicity study, groups of Sprague-Dawley [Crl:CD (SD)] rats (5/sex) were exposed (nose only) by inhalation route to organolignite for 4 hours at nominal concentrations of 2000 mg/m³. The particle size of the test material was reduced for testing in accordance with OECD guidelines. Animals were then 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 observation was considered to be normal for this strain and age of rat and was not considered an adverse effect. One male exhibited dark/discolored lungs, which was due to the color of the test material. This observation was not considered an adverse effect. The inhalation LC50 was determined to be > 2170 mg/m³ (equivalent to 2.17 mg/L) in males and females.

Justification for classification or non-classification

Based on evaluation of the data discussed above, organolignite does not meet the criteria for classification as an acute oral, dermal, or inhalation toxicant under CLP EU Regulation 1272/2008 (GHS aligned) because the reported LD50/LC50 values for this substance exceed the threshold for classification defined in the regulations.