Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No OECD Guideline and GLP defined; all essential data reported.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
The acute toxicity and primary irritancy of N-Benzyl-N,N-Dimethylamine
Author:
Ballantyne B, Dodd DE, Nachreiner, Myers RC.
Year:
1985
Bibliographic source:
Drug and Chemical Toxicology, 8; 43-56 (1985)
Reference Type:
other: Microfiche
Title:
Unnamed
Year:
1980
Report Date:
1980
Reference Type:
publication
Title:
Comparative acute toxicity and primary irritancy of various classes of amines
Author:
Myers R.C. et al.
Year:
1997
Bibliographic source:
Toxic Substance Mechanisms, 16: 151-193 (1997)

Materials and methods

Principles of method if other than guideline:
Undiluted BDMA was applied to the clipped dorsal skin of groups containing 4 male rabbits per group at doses of 0.5, 1.0, 1.4, 2.0 ml/kg bw. for 24 hours Animals were observed daily over a 14-day post application period for signs of toxicity. At the end of this time the survivors were sacrificed and subjected to autopsy examination.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.2 %
Density: 890 mg/ml at 25 C
Molecular Weight: 135.23
Boiling Point: 179.6°C
Vapor Pressure: 1.31 Torr at 20°C
1.82 Torr at 25°C
10.00 Torr at 55°C
50.00 Torr at 91°C
Flash Point: 57°C (Cleveland Open Cup)
Solubility: Readily soluble in aqueous acids, methanol, acetone and benzene. Water solubility, 0.12 g/dl.
Specific Gravity: 0.89 (25°C)
Saturated Vapor Concentration: 14430 mg/m³ (25°C)
Conversion Factors: 1 ppm= 5.53 mg/m³ (25°C, 760 Torr)
1 mg/m³= 0.181 ppm (25°C, 760 Torr)

Test animals

Species:
rabbit
Strain:
other: albino
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 3-5 months
- Weight at study initiation: 2.5-3.1 kg

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-80
- Humidity (%): 39-65
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The undiluted test material was applied on the clipped dorsal skin of rabbits and was maintained in contact with the skin by a polythene sheet and held in place with an adhesive dressing. Animals were immobilized during a 24-hr occlusion period. At the end of the contact period the polythene sheeting was removed, the skin gently wiped clean, and the area inspected for signs of local inflamation
Duration of exposure:
24 h
Doses:
0.5, 1.0, 1.4, 2.0 ml/kg bw = 445-890-1246-1780 mg/kg bw
No. of animals per sex per dose:
0.5 ml/kg bw = 4 animals,
1.0 ml/kg bw = 4 animals,
1.4 ml/kg bw = 4 animals,
2.0 ml/kg bw = 2 animals
Control animals:
not specified
Details on study design:
Undiluted BDMA was applied to the clipped dorsal skin of groups containing 4 male rabbits at doses of 0.5, 1.0, 1.4, 2.0 ml/kg bw. At the end of the contact period the polythene sheeting was removed, the skin gently wiped clean, and the area inspected for signs of local inflamation. Animals were observed daily over a 14-day post application period for signs of toxicity. At the end of this time the survivors were sacrificed and all rabbits in test were subjected to autopsy examination.
Statistics:
moving average method

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
1.66 mL/kg bw
95% CL:
1.35 - 2.04
Remarks on result:
other: ca. 1477 mg/kg bw ; based on death of all rabbits at 2.0 ml/kg bw with tremor and hyperactivity before death, edema and necrosis at the application site, and mottled appearance of liver and kidney; no other rabbit was affected by treatment
Mortality:
2.0 ml/kg bw: 4/4 within 2 days post application
no other animal died
Clinical signs:
Signs of toxicity at the highest test dose included tremors hyperactivity.
No other animal developed clinical signs
Body weight:
no data
Gross pathology:
On removal of the occlusive dressing edema and necrosis were seen at the site of application. this progressed to scab formation over the following
14-day observation period
Autopsy of dead animals revealed red mottled appearance to the liver and kidneys; otherwise there were no abnormalities

Any other information on results incl. tables

RS-Freetext:
Mortality:
Dose: 445 890 1246 1780
Deaths (%): 0 0 0 100
Time: - - - 1-2 d

LD50: 1.66 ml/kg (1.35-2.04) = 1477 mg/kg

Signs of toxicity:
Tremors, immediate hyperactivity, vocalisation, weight loss, only in the highest dose group, death within 1-2 days.
Edema and necrosis with formation of scabs at the site of application within the observation period of 14 d.

Gross necropsy:
Deaths: mottled appearance of liver and kidneys
Survivors: no abnormal findings

Applicant's summary and conclusion

Executive summary:

In an acute dermal toxicity study the undiluted test substance was applied to the clipped dorsal skin of groups containing 4 male rabbits/group at doses of 0.5, 1.0, 1.4, 2.0 ml/kg bw. The test material was maintained in contact with the skin by a polythene sheet held in place with an adhesive dressing. Animals were immobilized during a 24-hr occlusion period. At the end of the contact period the polythene sheeting was removed, the skin gently wiped clean, and the area inspected for signs of local inflammation. Animals were observed daily over a 14-day postapplication period for signs of toxicity. At the end of this time the survivors were sacrificed and subjected to autopsy examination. All animals died at the highest dose of 2.0 ml/kg bw, with a latency of up to 2 days. Signs of toxicity included tremors and hyperactivity. No signs of systmic toxicity were seen in animals following the application of 1.4 ml/kg bw and lower. On removal of the occlusive dressing, edema and necrosis were seen at the site of application of undiluted test substance to skin. This progressed to scab formation over the ensuing 14 days. Autopsy examination of the animals that died revealed a red mottled appearance to the liver and kidneys, but otherwise there were no abnormalities. The LD50 was determined to be 1.66 ml/kg bw (ca1477 mg/kg bw).