Benzyldimethylamine

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Detailed study summary and tables available (main text in japanese)

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Guidelines for 28-day Repeat Dose Toxicity testing of Chemicals (Japan)

Deviations:

yes

Remarks:

- recovery groups

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzyldimethylamine

EC Number:

203-149-1

EC Name:

Benzyldimethylamine

Cas Number:

103-83-3

Molecular formula:

C9H13N

IUPAC Name:

benzyldimethylamine

Details on test material:

TS-Freetext:
Purity: 99,93 wt%

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

no details given

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

male and female rats were given the different amountsdiluted in conr oil by gavage once daily over a period of 28 days

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 100, 200, 400 mg/kg bw/day
Basis:

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

male and female rats were fed with 0, 50, 100, 200, 400 mg7kg bw/day over a period of 28 days,
rats dosed with 50 and 100 mg/kg bw/day were killed immediately after cessation of treatment:
groups of rats dosed with 200 and 400 mg/kg bw/day were aloud to recover for 14 days and then examined accordingly

Positive control:

not required

Examinations

Observations and examinations performed and frequency:

clinical observation once a day
mortality body weight blood examinations hematology
clinical biochemistry, urinalysis

Sacrifice and pathology:

gross pathology, organ weight.microscopic examination:
brain, liver, kidney, spleen, adrenals,ovaries, testes, thymus,
respiratory system, integumentary system, cardiovascular system, reproductive system
hematopoietic system, urinary system, digestive system

Other examinations:

no data

Statistics:

Non-parametric analysis

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
mortality from week 2 at 400 mg/kg bw/d: males: 4/5; females.5/5
no control animal died
gross pathological examination revealed no obvious changes
histopathological examination:
inclusion bodies in hepatocytes (m+f); degeneration of adrenal cortex (f);

clinical signs.
100, 200 and 400 mg/kg bw/day, male and females: miosis
200, 400 mg/kg bw/day, male and female:: salivation
400 mg/kg bw/day, male and female: dirty fur
400 mg/kg bw/day, females: tremor before death
recovery period: 200, 400 mg/kg bw: clinical signs diappeared

BODY WEIGHT AND WEIGHT GAIN
400 mg/kg bw/day males: significantly depressed body weight.
274 g versus 334 g in control, no further information
recovery period: 361 g versus407 g in control , no further information

CLINICAL CHEMISTRY
200 mg/kg bw/day, male: not significant increase in total cholesterol which normalized during recovery period
72 mg/dl versus 51 mg/dl in controls
recovery period 53 mg/dl versus 57 mg/dl in controls
200 mg/kg bw/day, males, recovery period:
decreased Albumin/ Globulin ratio
1.06 (p<=0.05) versus 1.18 in controls
female, 200 mg/kg bw/day: significant increase in blood glucose which normalized during recovery period
116 mg/dl (p<=0.01) versus 91 mg/dl in controls
recovery period: 126 mg/dl versus 116 mg/dl in controls


ORGAN WEIGHTS (significant changes only)
males: 200 mg/kg bw/day
significantly increased absolute spleen weight but not in relative weight:
0,63 g versus 0.51 g in controls which normaluized during rcovery period
during recovery period significant increased adernal weights
absolute. 62 mg (p>=0.01)versus 51 mg
relative: 0.016 (p<=0.05) versus 0.013
female, 200 mg/kg bw/day
significantly increased liver weights which normalized during recovery:
absolute: 7.07 g (p<=0.05) versus 5.91g in controls
relative 3.251(p<= 0.05) versus 2.939

HISTOPATHOLOGY: NON-NEOPLASTIC
suvivors showed no histopathological changes

Effect levels

Dose descriptor:

NOEL

Effect level:

50 other: mg/kg

Sex:

male/female

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:
at 400 mg/kg bw 4/5 males and 5/5 females died within the treatment  period. Cause of deaths could not be determined.

Clinical signs:
100 mg/kg: m+f: miosis
200 mg/kg: m+f: miosis, salivation; reversible during                        recovery
400 mg/kg: m+f: miosis, salivation, dirty hair 
             f: premortal tremors
             m: reduced weight gain: ~20% after 4 weeks;                  partial recovery after end of treatment

Food consumption:
no effects

Hematology:
400 mg/kg: reduced white cell number (the 1 surviving male)

Clinical chemistry:
200 mg/kg: increased total cholesterol

Urinalysis:
100 mg/kg: increased urine volume (m)
200 mg/kg: increased urine volume (m+f)
400 mg/kg: increased urine volume (m)

Organ weights:
200 mg/kg: increased absolute weight (spleen, m; liver, f)
           increased relative weight (liver, f)
     after recovery:
           increased absolute weight (adrenals, m, slight)
           increased relative weight (adrenals, m, slight)
400 mg/kg: decreased absolute weight (spleen, m)

Histopathology:
Survivors: no effects
Deceased animals: inclusion bodies in hepatocytes (m+f); degeneration of  adrenal cortex (f);

Applicant's summary and conclusion

Executive summary:

N,N-Dimethylbezylamine was given by gavage to male and female Crj:CD (SD) rats in doses of 0 (corn oil), 50, 100, 200, 400 mg/kg bw/day diluted in corn oil over a period of 28 days. In addition, animals of the control group and animals treated with 200 and 400 mg/kg bw/day were obseserved after termination of treatment for further 2 weeks (recovery group). Mortalities of both males and females receiving 400 mg/kg were observed from week 2. Clinical observation revealed miosis in both sexes receiving 100 mg/kg and miosis and salivation in those receiving 200 and 400 mg/kg. Body weight gain was suppressed in males receiving 400 mg/kg. Slight increases in total cholesterol were observed in males receiving 200 mg/kg. Pathological examination revealed no abnormalities attributable to the test substance treatment. The NOEL for repeat dose toxicity is considered to be 50 mg/kg/day for both sexes (MHLW 1997).