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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline test and GLP
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
N,N-Dimethylbenzylamine (Desmorapid DB) no further data

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males 158.5-184.5 g femalew:116.1-153.9 g
- Housing: 5
- Diet ad libitum
- Water ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test article was administered daily by gavage for 28 days
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
the achieved concentration was measured during week 1 and week 2 the analytical procedure HUK624/1-01F
Duration of treatment / exposure:
28 days
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 6, 30, 150 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
according to the respective OECD guideline
Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily , full examination weekly

BODY WEIGHT: Yes
- Time schedule for examinations: once weekly

FOOD CONSUMPTION weekly:

WATER CONSUMPTION by visual appraisal:

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: week 4
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- Animals fasted: Yes
- Parameters
hemoglobin conc., MCV,RBC, MCH, MCHC, PCV, WBC, platlet count
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: week 4
- Animals fasted: Yes
- Parameters
alkaline phosphatase, GOT/AST, GPT/ALT, blood urea, BUN, Cholesterol, creatininem glucose, total bilirubin, triglyceride,
albumin, albumin/globulin ratio,
total protein, Ca, K, Na, inorganic phosphorus

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Organ weights
adrenals liver kidneys testes
left and right organs were weighed separately

HISTOPATHOLOGY: Yes
tissues from control and high dose animals initially

tissue preservation
adremals, aorta, brain (medullary and cerebellar and cortical sections),
colon (duodenum, caecum, jejunum rectum), kidneys, liver, lungs, lymph nodes (mandibular and nesenteric) ,
eyes and optic nerve, oesophageousm pancreasm prostatem salivary glands, seminal vesicles, spinal cord, stomach,
thymus, trachea, uterus including cervix, ovaries, pituitary gland, femur with bone marrow, mammary gland, sciatic nerve,
skin, spleen, testes with epididymides, thyroid with parathyroids urinary bladder
Other examinations:
no data
Statistics:
anlysis of variance, t-test, Kruskal-Wallis test, Wilcoxon test

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY
there were no clinical observations that were considered to be related to treatment
During week 4 1 control male died and in the intermediate dose 1 female
Both death were considered to result vrom blood sampling/anesthetic

BODY WEIGHT AND WEIGHT GAIN
The body weight gain of male and female rats was considered not to have been affected by treatment

HAEMATOLOGY and CLINICAL CHEMISTRY
The measured haematological and clinical chemistry parameters were considered to have remained unaffected by treatment

ORGAN WEIGHTS
Organ weights in test animals were in general comparable to organ weights of control animals

the absolute and relative testis weights for high dose group males were slightly higher han those of the controls.
However there was no histopathological correlate
Testis weights for the low and intermediate dose group males were similiar to those of the controls

GROSS PATHOLOGY and HISTOPATHOLOGY: NON-NEOPLASTIC
there were no histopathological findings of any unusual nature or incidence suggestive of target organ toxicity

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 150 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: There were no major differences between control and treated rats. The high dose group males had slightly higher testis weights than the controls. However there was no histopathological correlate

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The data were processed, where appropriate, to give group mean values and standard deviations. The nature of the data was considered to be such that statistical analysis would not have provided additional information.

Applicant's summary and conclusion

Executive summary:

In an test according to OECD TG 407 and GLP groups of male and female Crl:CD(SD)BR rats received N,N-Dimethylbenzylamine in corn oil by daily oral gavage at nominal dose levels of 6, 30 or 150 mg/kg bw/day. A further group of the same size received corn oil alone and served as control. There were no major differences between control and treated rats. The high dose group males had slightly higher testis weights than the controls. However there was no histopathological correlate. Therefore this finding was considered not to be of toxicological relvance. The NOAEL was determined to be 150 mg/kg bw/day (BG Chemie 1988).