(2-hydroxypropyl)trimethylammonium formate

Endpoint summary

Description of key information

In an OECD 423 study (2016) in rats the oral LD50 of Solvent-free Dabco TMR-2 was greater than 2000 mg/kg body weight.

In a non-guideline study (1976) equivalent to OECD guideline 401, the acute oral LD was found to be 11.3 ml/kg

In a non-guideline acute inhaltion study in rats (1976()the LC50  was found to be greater than 7.5 mg/ litre (7500 mg/m3)

In a non-guideline acute dermal toxicity study in rats (1976) the acute dermal LD50 greater than 2.0 gm/kg ((2000 mg/kg)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 Aug 2016 - 30 Sep 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Acute Toxic Class Determination (Oral) in Rats

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Initially, three healthy female Sprague Dawley rats were dosed orally with Solvent-free Dabco TMR-2 Batch# chernil.20160628.B at 2000 mg/kg. In addition, three healthy males were dosed as a confirmatory group at 2000 mg/kg. The rats were observed at 15 minutes, 1, 2 and 4 hours post-dosing and once daily for 14 days for toxicity and pharmacological effects, and twice daily for mortality. Body weights were recorded immediately pretest, weekly and at termination. All animals were examined for gross pathology. The test article was assigned to a toxic category based on the mortality response noted.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Identity : Solvent-free Dabco TMR-2 Batch# chernil.20160628.B
Test Article
Characterization : See Appendix A for Test Article Characterization.
Supplied by : Air Products and Chemicals, Inc.
Date Received : 18 Jul 2016
Storage : Room temperature and humidity
Description : Clear colorless liquid
Specific Gravity : 1.14
Sample Preparation : Used as received

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animals were received from Charles River, Raleigh NC and Stone Ridge NY, on 26 Jul 2016 and 09 Aug 2016.
The pretest body weight range was 231 - 254 grams for males and 192 - 207 grams for females.

The animals were identified by cage notation and indelible body marks, and housed in suspended wire cages; five per sex per cage prior to dosing and three per sex per cage following dosing. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rat Chow (Diet #5012) was freely available except for 16-20 hours prior to dosing. Water was available ad libitum. The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a 12-hour light/dark cycle, and was kept clean and vermin free.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test article was used as received and the dose was based on the sample weight as calculated from the specific gravity. A single dose was administered orally by syringe and dosing needle at a dose level of 2000 mg/kg to three female rats and three male rats.

Doses:

All animals dosed at 2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

In Vivo - Animals were observed at 15 minutes, 1, 2 and 4 hours post-dosing and once daily for 14 days for toxicity and pharmacological effects and twice daily for mortality. Body weights were recorded immediately pretest, weekly and at termination.

Post Mortem – All animals were humanely sacrificed using CO2 and were examined for gross pathology following study termination

Preliminary study:

N/A

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

All three female and three male rats survived following a single 2000 mg/kg oral dose.

Clinical signs:

other: No abnormal physical signs were observed among four out of six animals. One female had chromorhinorrhea on Day 11 and one male had diarrhea and soiling of the anogenital area on Day 0.

Gross pathology:

The gross necropsy revealed no observable abnormalities.

Other findings:

No abnormal physical signs were observed among four out of six animals. One female had chromorhinorrhea on Day 11 and one male had diarrhea and soiling of the anogenital area on Day 0.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of Solvent-free Dabco TMR-2 is greater than 2000 mg/kg of body weight in rats.
GHS: Not classified

Executive summary:

Three healthy female Sprague Dawley rats were dosed orally with Solventfree Dabco TMR-2 Batch# chernil.20160628.B at 2000 mg/kg. In addition, three healthy males were dosed as a confirmatory group at 2000 mg/kg. The rats were observed at 15 minutes, 1, 2 and 4 hours post-dosing and once daily for 14 days for toxicity and pharmacological effects, and twice daily for mortality. Body weights were recorded immediately pretest, weekly and at termination. All animals were examined for gross pathology.

All three female and three male rats survived following a single 2000 mg/kg oral dose. No abnormal physical signs were observed among four out of six animals. One female had chromorhinorrhea on Day 11 and one male had diarrhea and soiling of the anogenital area on Day 0. All six animals gained body weight by study termination. The gross necropsy revealed no observable abnormalities.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

November 18, 1976 - December 29, 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Five groups of five male albino rats of the Sherman-Wistar Strain weighing between 200 and 300 gm were employed in this study.

The rats were deprived of food but not water for 24 hours prior to dosing. Each animal was weighed and dosed by direct administration of the experimental material int o the stomach by means of a syringe and dosing needle.

Five groups of five male albino rats of the Sherman-Wistar Strain weighing between 200 and 300 gm were employed in this study.
The rats were deprived of food but not water for 24 hours prior to dosing. Each animal was weighed and dosed by direct administration of the experimental material int o the stomach by means of a syringe and dosing needle.
Following administration the animals were allowed food and water ad libitum for the 14 day observation period during which time the rats were observed for signs of toxicity and mortalities .

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Sherman-Wistar

Sex:

male

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

5 dose levels were used:
1.0 ml/kg
2.0 ml/kg
4.0 ml/kg
8.0 ml/kg
16.0 ml/kg

No. of animals per sex per dose:

Five groups of five male albino rats

Control animals:

not specified

Preliminary study:

N/A

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 mL/kg bw

Based on:

test mat.

Mortality:

All 5 animals in the highest dose group (16 ml/kg)

Clinical signs:

other: There were no unusual behavioral signs noted.

Gross pathology:

Gross pathologic examination revealed liver congestion.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD was found to be 11.3 ml/kg with 19/20 Confidence Limits of Prom 8.0 to 16.0 ml/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Based on 2016 Guideline study (OECD 423)

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:

November 18, 1976 - December 29, 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

A group of ten male albino rats was used in this study. The rats were placed in a 70 liter all glass exposure chamber and exposed to a saturated atmosphere of the test material in air for one hour.
The material was administered as an aerosol with particles 3-5 microns in diameter.

The rate of flow was 10.0 liters per minute at a temperature of 71°f (21.67°c).
The air was passed through a desicant prior to being passed through the test material.
By differential weighing it was calculated that the rats were subjected t o a concentration of 7.5 m g / liter during the exposure period. This is an average value over the one hour period.

GLP compliance:

not specified

Test type:

traditional method

Limit test:

no

Species:

rat

Strain:

not specified

Remarks:

albino

Sex:

male

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

> 3 - <= 5 µm

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

1 h

Concentrations:

7.5 mg / liter

No. of animals per sex per dose:

10 males in one dose group

Control animals:

no

Sex:

male

Dose descriptor:

LC50

Effect level:

> 7.5 mg/L air

Based on:

test mat.

Exp. duration:

1 h

Mortality:

No mortalities observed after 14 days

Clinical signs:

other: No behavioural abnormalities observed.

Body weight:

Not recorded

Gross pathology:

Gross parthologic examonation of all animal revealed nothing remarkable.

Interpretation of results:

GHS criteria not met

Conclusions:

In this study the LC50 for Dabco TMR-2 was found to be greater than 7.5 m g / liter .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

7 500 mg/m³ air

Quality of whole database:

1976 non-guideline study

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:

November 18, 1976 - December 29, 1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

not specified

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

The sample was dosed as supplied.

Species:

rabbit

Strain:

not specified

Remarks:

Albino Rabbits

Sex:

male/female

Details on test animals or test system and environmental conditions:

N/A

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

All animals had their backs clipped free of hair 24 hours prior to testing . One half of the animals had their backs abraded prior to dosing.

All rabbits were weighed and the correct amount of experimental material was applied to the back of each animal. Treated areas were covered with large gauze patches and an impervious material was wrapped snugly around the trunk of each animal.
The dressings were removed after twenty-four hours. Excess material was removed and the approximate amount remaining was noted. The animals were observed for a 14 day period for signs of toxicity and for mortalities. Gross autopsies were performed
on a ll animals that died during the 14 day observation period.

Duration of exposure:

24 hours

Doses:

All animals were dosed at 2.0 g/kg (2000 mg/kg)

No. of animals per sex per dose:

5 male and 5 female animals in one dose group (2000 mg/kg)

Control animals:

no

Details on study design:

One group of ten albino rabbits (5 male and 5 female) weighing between 2.5 and 3.5 kg. each were employed in this study.
After the dosing period, the occlusion was removed and the animals were observed for a 14 day period for signs of toxicity and for mortalities. Gross autopsies would be performed on any animals that died during the 14 day observation period.

Statistics:

N/A

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortaities were observed

Clinical signs:

other: No unusual clinical or behavioral signs were noted.

Gross pathology:

Gross pathologic examination revealed nothing remarkable.

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, TMR-2 was found to have an acute dermal LD50 greater than 2.0 gm/kg ((2000 mg/kg)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

1976 non-guideline study