Dimethylamine-borane (1:1)

Acute Toxicity: dermal

Administrative data

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

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1979-07-31 to 1979-10-03

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

see box "principles of method if other than guideline"

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 402 "Acute dermal Toxicity"

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 cm²
- 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 cm²
- Occlusive

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No. of test material: dimethylamine-borane, Lot. No. 40-37 was received from Callery Chemical Company.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Rabbits of the New Zealand White variety weighing 2.5 kg or greater were obtained and acclimated to the laboratory a minimum of seven days. Rabbits were individually housed in suspended cages with feed and water freely available.

Type of coverage:

occlusive

Preparation of test site:

other: clipped and abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

24 h

Observation period:

14 days

Number of animals:

4 per dose group (2 abraded, 2 with intact skin)

Details on study design:

TREATMENT:
Prior to application of the test substance, one half (2) of the rabbits in each group received a series of abrasions with a sterile needle through the epidermis and two rabbits remained intact. The trunk of each rabbit was wrapped with an impervious material taped in place to form a reservoir over the test skin site. The test material was introduced onto the skin at the dose levels indicated below. 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. Wrappings were removed after 24 hours and the test material was gently washed from the back.

OBSERVATIONS:
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 weight was recorded at dosing and at 14 days for the survivors. Animals found dead or euthanized at 14 days were subjected to a macroscopic examination of the viscera.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

There were no significant signs of dermal irritation.

Other effects:

The LD50 was calculated to be 210 mg/kg body weight with 95% confidence limits of 156-284 mg/kg. 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. No effects on body weight gain during the entire course of the study.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study conducted in rabbits, no signs of dermal irritation were observed.

Executive summary:

In an acute dermal toxicity study similar to OECD 402, dimethylamine-borane was applied occlusively to the abraded and intact skin of New Zealand White rabbits at concentrations of 126, 158, 200, 251, 316 and 398 mg/kg body weight for 24 hours. Afterwards, the test material was washed off. The animals were observed for 14 days for clinical signs and mortality including a daily scoring for erythema and edema. Body weight was recorded at dosing and at the end of the study for the survivors. Animals found dead or euthanised at 14 days were subjected to a macroscopic examination of the viscera. The LD50 was calculated to be 210 mg/kg body weight with 95% confidence limits of 156 - 284 mg/kg bw. 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. All surviving animals gained body weight during the course of the study. There were no significant signs of dermal irritation noted throughout the study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Test guideline 1

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"

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

Dimethylamine-borane (1:1)

EC Number:

200-823-7

EC Name:

Dimethylamine-borane (1:1)

Cas Number:

74-94-2

Molecular formula:

C2H10BN

IUPAC Name:

N-Methylmethanamine-borane (1:1)

Specific details on test material used for the study:

- Lot: 40-37

Test animals

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.

Administration / exposure

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.

Results and discussion

Effect levels

Effect levels 1

Sex:

not specified

Dose descriptor:

LD50

Effect level:

210 mg/kg bw

Based on:

test mat.

95% CL:

>= 156 - <= 284

Effect levels 2

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.