Dipropylamine

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: see 'Remark'

Remarks:

well conducted study similar to guideline (feeding; 14-day treatment period; no heamatology, clinical chemistry, urinanalysis, neurobehavioural examination, ophthalmoscopic examination and water consumption; no data on analytical verification of doses)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Version / remarks:

14-day treatment period (feeding)

Deviations:

yes

Remarks:

no heamatology, clinical chemistry, urinanalysis, neurobehavioural examination, ophthalmoscopic examination and water consumption

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dipropylamine

EC Number:

205-565-9

EC Name:

Dipropylamine

Cas Number:

142-84-7

Molecular formula:

C6H15N

IUPAC Name:

dipropylamine

Details on test material:

- Name of test material (as cited in study report): Di-n-propylamine
- Analytical purity: assumed 100% active ingredients
- Lot/batch No.:Reference 1578-92
No additional details provided

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: the study utilised 40 male and 40 female cesarean derived albino rats (Spragur-Dawley, Charles River Laboratories, Wilmington, Massachusetts)
- Weight at study initiation: 158 - 194 g (males) and 120-145 g (females)
- Housing: individually in elevated wire mesh cages
- Diet (e.g. ad libitum): basal laboratory diet consisting of Purina Laboratory Rat Chow
- Water (e.g. ad libitum): water (not further specified)
No additional details provided

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): Fresh diets were prepared weekly and thoroughly mixed in a twin-shell Patterson-Kelley blender. Dosages were adjusted each week according to the most recent group body weight and food consumption data
- Mixing appropriate amounts with (Type of food): appropriate amounts of the test material were mixed with the basal diet on a weight-per-weight basis
- Storage temperature of food: not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 days

Frequency of treatment:

continuously in feed.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 75, 150 or 300 mg/kg/bw
Basis:
other: it is stated that diet was prepared to provide the designated dosage levels of 75, 150 and 300 mg/kg of weight per day (see Table 1)

No. of animals per sex per dose:

10 (see Table 1)

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: no data
- Rationale for animal assignment (if not random): the animals were divided into 4 groups per sex based on individual body weights so that homogeneous distribution of weight ranges and mean weights was obtained between groups (see Table 1)
- Rationale for selecting satellite groups: no satellite groups included in the study

Positive control:

none used

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: all animals were observed daily for mortality

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: gross signs of systemic toxicity and/or pharmacological effect were recorded weekly

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY AND HISTOPATHOLOGY: Yes; all animals were sacrificed at the end of the 2-week treatment by exsanguination under sodium pentobarbital anesthesia. Necropsy was performed and the liver, kidneys and any abnormal tissues were removed and preserved in 10% neutral buffered formalin for subsequent histopathological examination

Other examinations:

none

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

with the exception of one mild level male animals, which was noted to have a hunched appearance at week 1, no remarkable signs were observed in any of the animals throughout the study. Survival was 100% in all groups

Mortality:

no mortality observed

Description (incidence):

with the exception of one mild level male animals, which was noted to have a hunched appearance at week 1, no remarkable signs were observed in any of the animals throughout the study. Survival was 100% in all groups

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

a slight dose-related decrease in the rate of body weight gain was observed in treated males at weeks 1 and 2 and in treated females at week 1 (see Table 3). The decrease in body weight gain among the high dose level animals was approximately 20% in males

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

the mean food consumption values of treated males were slightly less than those of the control groups at weeks 1 and 2

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

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

observed effects consisted of incidental kidney changes only and included dilation of the pelvis, cystic areas in the cortex and darkening of the medulla.

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

microscopic evaluations of the liver and kidney sections did not reveal any compound-related histomorphologic alterations

Histopathological findings: neoplastic:

no effects observed

Details on results:

HISTOPATHOLOGY: NON-NEOPLASTIC
Spontaneous disease lesions consisted of microgranulomas in the liver sections and minimal to slight focal interstitial nephritis in the kidneys characterized by mononuclear inflammatory cells, regenerative tubule epithelium and occasional dilated renal tubules. Dilation of the renal pelvis was noted in small numbers of treated rats (2 in group 2, 3 in group 3 and 3 in group 4); however, this is considered tan incidental finding unrelated to treatment.

Effect levels

1

Dose descriptor:

LOEL

Effect level:

300 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: body weight gain (9% reduction)

2

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: high dose

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 2: Mean body weight and food consumption

Sex	Dose level (mg/kg bw per day)	Mean body weight and food consumption for indicated test groups and time period (± SD)
		Body weight (g)			Food consumption
		Initial	Week 1	Week 2	Week 1	Week 2
Male animals	0	181.0±7.6	240.9±18.2	298.6±25.9	173.6±17.1	187.9±19.0
	75	180.9±8.3	234.7±14.7	290.2±19.6	161.8±13.1	176.2±14.8
	150	179.9±9.6	228.9±21.4	288.5±19.3	165.0±17.5	181.6±18.6
	300	180.1±9.2	221.4±11.5	274.5±12.9	150.1±14.8	171.3±13.1
Female animals	0	133.1±7.8	160.7±10.9	176.4±13.5	119.7±9.4	121.8±10.0
	75	132.8±7.6	158.1±8.9	178.5±11.1	118.1±9.5	127.1±10.3
	150	132.8±7.3	157.1±9.2	181.5±14.7	124.6±15.2	130.6±17.2
	300	133.0±8.4	153.3±11.1	173.7±12.9	115.3±11.9	128.0±9.3

Table 3: Mean body weight gains

Sex	Dose level (mg/kg bw per day)	Mean body weight gains (g) compared to initial body weight
		After 1 week	After 1 weeks
Male animals	0	+59.9	+117.6
	75	+53.8	+109.3
	150	+49.0	+108.6
	300	+41.3	+94.4
Female animals	0	+27.6	+42.9
	75	+25.3	+45.7
	150	+24.3	+48.7
	300	+20.3	+40.7