N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1975

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Range-finding study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

EC Number:

221-220-5

EC Name:

N,N,N',N'-tetramethyl-2,2'-oxybis(ethylamine)

Cas Number:

3033-62-3

Molecular formula:

C8H20N2O

IUPAC Name:

{2-[2-(dimethylamino)ethoxy]ethyl}dimethylamine

Test material form:

liquid

Specific details on test material used for the study:

CAS 3033-62-3 (2,2'oxybis(N,N-dimethyl ethanamine),
purity not indicated

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Harlan Wistar Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Age: 30 days of age at study initiation

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: dietary feed

Details on oral exposure:

-The test substance was added to ground Purina Laboratory Chow and fed in the diet
- Post exposure period: none

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

- Dosage goal 0, 0.15, 0.35, and 0.85 gm/kg
- Concentration in diet:
males: 0, 0.13, 0.28, 0.69%;
females:0.14, 0.33, 0.80%
- Diet consumed:
males: 17.8, 10.1, and 5.4 gm/rat/day;
females: 14.8, 8, 4.4 gm/rat/day
- Dosage attained:
males: 0.15, 0.22, and 0.33 gm/kg/day;
females: 0.15, 0.22, and 0.32 gm/kg/day

Duration of treatment / exposure:

7 days

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

150 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

220 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

320 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5/sex/dose

Control animals:

yes

Positive control:

none

Examinations

Observations and examinations performed and frequency:

- Clinical signs and mortality: daily
- Body weight: on day 1 (prior to exposure), 5, and 7 (prior to termination)
- Food consumption: monitored daily

Sacrifice and pathology:

ORGANS EXAMINED AT NECROPSY (GROSS AND MICROSCOPIC):
- Organ weights: liver, kidneys
- Gross pathology: Lungs, Liver, Kidneys, and Spleen
- Microscopic examination: lung, liver, kidneys, heart, spleen, adrenal, thyroids, parathyroids, trachea, esophagus, stomach, duodenum, pancreas, colon, urinary bladder, brain, pituitary and prostate, testicle, epididymis, uterus and ovary from high dosage and control groups; lung, liver, kidneys, heart, spleen, adrenal, thyroids, parathyroids, trachea, esophagus and brain from the two lower dosage groups

Statistics:

Not specified

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Description (incidence):

1 female and 2 males from the high dose group; all other animals survived

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

significantly depressed body weight in both males and females at 220 and 320 mg/kg/day

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

concentration-related reduction in both sexes

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Significant decrease in kidney weight in males at 220 and 320 mg/kg/day; slight increase in liver weight in males at 320 mg/kg/day; significant increase in liver weight relative to body weight in males and females at 320 mg/kg/day; decreased absolute kidney weights in females at 320 mg/kg/day; At the 220 mg/kg/day level, liver weights of males were depressed (opposite of effect at 320 mg/kg/day)

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Treatment-related findings were limited to the skin and kidneys

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Lesions of the lung, liver and stomach were associated with the two highest dosage levels; interstitial proliferative pneumonia, central fat vacuolization of hepatic cord cells and vacuolated smooth muscle fibers, respectively. No significant effects were associated with 150 mg/kg/day.

Histopathological findings: neoplastic:

no effects observed

Other effects:

not specified

Effect levels

Dose descriptor:

NOEL

Remarks:

systemic toxicity

Effect level:

150 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

histopathology: non-neoplastic

organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

In this K4, dose range finding study in rats, an NOEL for systemic toxicity is established at 150 mg/kg/day . An LOAEL for local effects is established at 220 mg/kg/day.