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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: No OECD Guideline or GLP defined; very limited documentation; few experimental details.

Data source

Reference
Reference Type:
publication
Title:
Untersuchungen zur Toxizität von Dimethylbenzylamin
Author:
Stasenkova K.P. et al.
Year:
1963
Bibliographic source:
Toksikologia Novykh Promyshlennykh Khimichiskich Veschtestv 5: 6-20 (1963); (Translation of a russian original)

Materials and methods

Principles of method if other than guideline:
subchronic inhalation study in rats; Parameters: body weights, general observation, hematology, blood pressure, hippuric acid,
neural senisivity (senistivity of leg muscles to stimulation by electricity(no details reported)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
no data

Test animals

Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
no further data
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
concentration determined by detection of the formation of a practically insoluble salt of molybdophosphoric acid
Duration of treatment / exposure:
2h per day; 3 months
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
100 - 200 mg/m³
Basis:

No. of animals per sex per dose:
no data
Control animals:
not specified
Details on study design:
no further data
Positive control:
no data

Examinations

Observations and examinations performed and frequency:
Parameters: body weights, general observation, hematology, blood pressure, hippuric acid,
neural senisivity (senistivity of leg muscles to stimulation by electricity(no details reported)
Sacrifice and pathology:
at the end of the exposure period gross and histopathological examination
Other examinations:
no data
Statistics:
no data

Results and discussion

Results of examinations

Details on results:
Mortality:none
Body weights:no effects
General observation: no differences to control animals
Hematology: slight increase of reticulocytes(~20%)
Blood pressure: decrease after the end of the exposure period
Hippuric acid: no effects
Neural senisivity: slight increase at the end of treatment period

Necropsy: no gross pathological findings
Microscopy:
Respiratory tract:
signs of local irritation in trachea and bronchi, muscular
hypertrophy of bronchi, perivascular edema, hyperplasia of perivascular
lymphoid tissue, focal fibrosis and emphysema of the lungs.
Kidneys:
slight dysthrophy of tubuli, stimulation of lymphatic tissue
Liver:
fatty dystorphy, stimulation of lymphatic tissue
Spleen:
medullary reduction of lymphoid tissue, slight edema

Effect levels

Dose descriptor:
conc. level:
Effect level:
>= 100 - <= 200 mg/m³ air
Sex:
not specified
Basis for effect level:
other: see 'Remark'

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

RS-Freetext:
Mortality: none
Body weights: no effects
General observation: no differences to control animals
Hematology: slight increase of reticulocytes(~20%)
Blood pressure: decrease after the end of the exposure period
Hippuric acid: no effects
Neural senisivity: slight increase at the end of treatment period
Necropsy: no findings

Microscopy:
Respiratory tract: signs of local irritation in trachea and bronchi, muscular hypertrophy of bronchi, perivascular edema, hyperplasia of perivascular lymphoid tissue, focal fibrosis and emphysema of the lungs.
Kidneys: slight dysthrophy of tubuli, stimulation of lymphatic tissue
Liver: fatty dystorphy, stimulation of lymphatic tissue
Spleen: medullary reduction of lymphoid tissue, slight edema

Applicant's summary and conclusion

Executive summary:

In a limited subchronic inhalation study in rats the following concentrations were used:100 - .200 mg/m³. Parameters checked were body weights, general observation, hematology, blood pressure, hippuric acid, neural senisivity (senistivity of leg muscles to stimulation by electricity (no details reported)). No mortality occurred. Detectable tracheitis and bronchitis with emphysema as well as degeneration of the tubule epithelium in the kidney and fatty degeneration of the liver cells was reported. The functional effects described included a decrease in the neuromuscular threshold of stimulation and a decrease in blood pressure. General behaviour , weight gain and hematological parameters were not altered (Stasenkova1963). However, this study is unsuitable for the use in the evaluation of the systemic toxicity of N,N-dimethylbenzylamine on repeated administration becaus of inadequate reporting of the study design and results (BG Chemie 1995)