Dimethylamine-borane (1:1)

Endpoint summary

Description of key information

The acute oral LD50 value of dimethlylamine-borane in rats was reported to be 59.2 mg/kg bw in a publication by Levinskas (1955).

Via the dermal route the acute LD50 value of the test item was determined to be 210.0 respectively 398.0 mg/kg bw in two different in vivo studies similar to OECD 402. In a worst case approach, a dermal LD50 value of 210 mg/kg bw is assumed.

In a review article by Roush (1959) an intraperitoneal LD50 value of dimethylamine-borane in rats of 50.0 mg/kg bw has been reported.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

No guideline available, study was done before guidelines were published.

GLP compliance:

no

Limit test:

yes

Specific details on test material used for the study:

- Melting point: 35.5 - 36.0 °C
- Physical state at room temperature: white crystalline solid

Species:

rat

Strain:

other: CFW

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult
- Weight at study initiation: 200-280 g
- Animals fasted for 18 hours

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

- 24 hours exposure for calculating LD50

Doses:

no data

No. of animals per sex per dose:

no data

Control animals:

not specified

Details on study design:

Adult rats were dosed at four different levels.

Statistics:

The LD50 values were calculated by the moving average method of Thompson.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

59.2 mg/kg bw

Based on:

test mat.

Mortality:

no data

Clinical signs:

other: no data

Gross pathology:

no data

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

In conclusion, the oral LD50 value in rats after treatment with dimethylamine-borane is determined to be 59.2 mg/kg bw.

Executive summary:

In an acute oral toxicity study, adult CFW rats (male) were given a single oral dose of dimethylamine-borane. An oral LD₅₀ of 59.2 mg/kg bw has been determined.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

59.2 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

to 1979-10-03

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

see box "principles of method if other than guideline"

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 404 (Acute Dermal Irritation/ Corrosion)

Deviations:

yes

Remarks:

see box "principles of method if other than guideline"

Principles of method if other than guideline:

Deviations from OECD 404:
- Exposure: 24 h
- Application area: 100 cm^2
- Occlusive
- Tested on the intact and abraded skin

Deviations from OECD 402:
- 4 Animals per dose group (abraded and intact skin 2 each)
- Application area: 100 cm^2
- Occlusive

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Specific details on test material used for the study:

- Lot: 40-37

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

Twenty-four albino rabbits of the New Zealand White variety weighing apprioxmately 2.5 kg or greater were obtained and acclimated to the laboratory for a minimum of seven (7) days. Rabbits were individually housed in suspended calges with feed and water freely available. The upper back area of all animals was clipped free of fur with an electric clipper.

Animal Care/Diet:
Animal husbandry will be conducted in accordance with the "Guide for Care and Use of Laboratory Animals," DHEW Publication 78-23.
Rabbits will receive Landmark Rabbit Feed on a daily basis. Tap water will be freely available. No contaminants are suspected that would interfere with the interpretation of study results.

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

Prior to application of the test substance, one half of the rabbits received a series of abrasions, with a sterile needle, through the epidermis. The trunk of each rabbit was wrapped with an impervious material taped in place to form a reservoir over the test skin site. During application, the rabbits were kept in a restrainer device and later were fitted with a collar to prevent ingesting the material and returned to their respective cage.

Duration of exposure:

24 h

Doses:

126, 158, 200, 251, 316 and 398 mg/kg body weight

No. of animals per sex per dose:

2 intact and 2 abraded rabbits per dose

Control animals:

no

Details on study design:

During application, the rabbits were kept in a restrainer device and later were fitted with a collar and returned to their respective cages. Wrappings were removed after 24 hours and the test material was gently washed from the back.
The rabbits were observed immediately after treatment, at four hours and daily for 14 days for signs of illness and mortality. Dermal reactions were scored daily for erythema and edema. Body weights were recorded at dosing and at 14 days for the survivors. Animals found dead or those euthanized were subjected to a macroscopic examination of the viscera.

Sex:

not specified

Dose descriptor:

LD50

Effect level:

210 mg/kg bw

Based on:

test mat.

95% CL:

>= 156 - <= 284

Sex:

not specified

Dose descriptor:

LD0

Effect level:

126 mg/kg bw

Based on:

test mat.

Mortality:

The LD50 is calculated to be 210 mg/kg body weight with 95% confidence limits of 156-284 mg/kg. For detailed results see Table 1 in "Any other information on results incl. tables

Gross pathology:

No macroscopic changes were noted at necropsy which could be attributed to the test material at the highest dose levels. All four rabbits showed uneven pitted appearance in the cortex of the kidney at the lowest level.

Other findings:

No significant dermal reactions were observed.

Table 1: Mortality

mg/kg	No. Dead/No. Dosed
398	4/4
316	3/4
251	2/4
200	3/4
158	2/4
126	0/4

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

In this acute dermal toxicity study, the dermal LD50 value in rabbits after treatment with dimethylamine-borane was 210 mg/kg body weight.

Executive summary:

In an acute dermal toxicity study similiar to OECD 402, groups of 4 New Zealand White rabbits (2 with intact, 2 with abraded skin) were dermally exposed to dimethylamine-borane for 24 hours at doses of 389, 316, 251, 200, 158 and 126 mg/kg body weight.  Animals then were observed for 14 days. The dermal LD50 was determined to be 210 mg/kg bw. There were no treatment related clinical signs and necropsy findings. All surviving rabbits gained weight during the course of the study.

Based on this study, dimethylamine-borane is of slight toxicity. Based on the dermal LD50 of 210 mg/kg bw, the test item does warrant for classification as Acute Tox Cat. 3 according to CLP Criteria.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

210 mg/kg bw

Additional information

In an acute oral toxicity study by Levinskas (1955), groups of rats were given a single dose of Dimethylamine-borane. Based on the mortality, an oral LD₅₀ of 59.2 mg/kg bw was determined. Based on these results, the test item Dimethylamine-borane is of slight toxicity and does warrant for classification as Acute Tox. Cat. 3 according to CLP criteria.

In an acute dermal toxicity study similar to OECD 402, groups of 4 New Zealand White rabbits (2 with intact, 2 with abraded skin) were dermally exposed to Dimethylamine-borane for 24 hours at doses of 389, 316, 251, 200, 158 and 126 mg/kg body weight. Animals then were observed for 14 days. The dermal LD₅₀ was determined to be 210 mg/kg bw. There were no treatment related clinical signs and necropsy findings. All surviving rabbits gained weight during the course of the study.

Based on this study, Dimethylamine-borane is of slight toxicity. Based on the dermal LD₅₀ of 210 mg/kg bw, the test item does warrant for classification as Acute Tox Cat. 3 according to CLP criteria.

In a second acute dermal toxicity study similar to OECD 402, groups of 6 New Zealand White rabbits (3 with intact, 3 with abraded skin) were dermally exposed to Dimethylamine-borane for 24 hours at doses of 389, 282, and 200 mg/kg body weight.  Animals then were observed for 14 days. The dermal LD₅₀ was determined to be 398 mg/kg bw. There were no treatment related clinical signs and necropsy findings. All surviving rabbits gained weight during the course of the study.

Based on this study, Dimethylamine-borane is of slight toxicity. Based on the dermal LD₅₀ of 398 mg/kg bw, the test item does warrant for classification as Acute Tox Cat. 3 according to CLP Criteria.

In a review article by Roush (1959) an intraperitoneal LD₅₀ value of Dimethylamine-borane in rats of 50.0 mg/kg bw has been reported. The rats showed progressive depression leading to coma and death was apparently respiratory.

Justification for classification or non-classification

Based on the dermal LD₅₀ value of 210.0 mg/kg bw determined in an in vivo study similar to OECD 402 and the oral LD₅₀ value of 59.2 mg/kg bw published in a review article, the test item dimethylamine-borane does warrant for classification as Acute Tox. Cat. 3 (H301 for acute oral toxicity and H311 for acute dermal toxicity) according to CLP criteria.