Fatty acids, C16-18 and C18-unsatd., Bu esters

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

1953

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable published study, basic data given (analytical purity of test substance not specified, only limited parameters evaluated (no clinical chemistry, urinalysis, behavioral examinations), limited documentation).

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Toxicity of butyl stearate, dibutyl sebacate, dibutyl phthalate, and methoxyethyl oleate

Author:

Smith, C.C.

Year:

1953

Bibliographic source:

Arch Ind Hyg Occup Med 7(4): 310-318

Reference 2

Reference Type:

secondary source

Title:

Final report on the safety assessment of Butyl stearate, Cetyl stearate, Isobutyl stearate, Isocetyl stearate, Isopropyl stearate, Myristyl stearate, and Octyl stearate

Author:

Busch J.T.

Year:

1985

Bibliographic source:

J Am College of Toxicol 4: 107-146

Reference 3

Reference Type:

secondary source

Title:

Palmitic Acid 2-ethylhexyl Esters Category of the Aliphatic Esters Chemicals (Test Plan and Robust Summaries for Substances in the HPV Test Plan)

Author:

US-EPA (American Chemistry Council’s Aliphatic Esters Panel)

Year:

2010

Bibliographic source:

High Production Volume (HPV) Chemical Challenge Program (201-16834B and 201-14977E)

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of male Sprague-Dawley rats were treated with the test item offered via feed during 2 years. 16 animals per dose level were used. The tested dose levels were 0.01, 0.05, 0.25, 1.25 and 6.25%, but only data of the 2 highest dose levels were considered for reporting.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butyl stearate

EC Number:

204-666-5

EC Name:

Butyl stearate

Cas Number:

123-95-5

Molecular formula:

C22H44O2

IUPAC Name:

butyl stearate

Details on test material:

- Name of test material (as cited in study report): Butyl stearate
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 65-66 g

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

2 years

Frequency of treatment:

continously in diet

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1.25 and 6.25%
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2500 and 6000 mg/kg bw/day
Basis:
other: (corresponding daily doses)

No. of animals per sex per dose:

16

Control animals:

yes, plain diet

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were measured twice weekly during the first month, thereafter at weekly intervals.

FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food intakes were measured twice weekly during the first month, thereafter at weekly intervals.

HAEMATOLOGY: Yes
- Time schedule for collection of blood: In the interval between 1 and 2 years, animals were killed whenever they approached a state of debility which suggested that death might be imminent. In such cases smears of peripheral blood and bone marrow were examined.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, in the interval between 1 and 2 years, animals were killed whenever they approached a state of debility which suggested that death might be imminent. In such cases the following organs were subjected to gross pathological examination: portions of the lungs, heart, liver, spleen, adrenals, kidneys, stomach, small intestine, thyroid, and brain.

HISTOPATHOLOGY: Yes, sections of various organs were prepared from the sacrificed animals mentioned above, for microscopical examination. Therefore, heart, spleen, adrenals, stomach, small intestine, thyroid, and brain were fixed in formalin, sectioned from paraffin, and stained with hematoxylin and eosin.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

slight changes in ratio of types of leucocytes in both, control and treated animals (non adverse)

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

non adverse

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

non adverse

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
No significant differences were observed between treated and control groups.

BODY WEIGHT AND WEIGHT GAIN
No substance related effects were observed.

HAEMATOLOGY
As the animals increased in age, slight changes in distribution of leucocytes were found, but these trends occurred in both the control and the treatment groups.

GROSS PATHOLOGY
Following gross pathology lesions were observed in animals killed at various time points during the experiment: acute and chronic inflammatory changes in the lungs, nephrosis in which the kidneys were enlarged and tan in colour, and fatty changes in the liver. Further pathological changes, such as tumors, infections of the ear and preputial glands, and an arteritis similar to periarteritis nodosa, occurred less frequently. These changes were found primarily in older animals.

HISTOPATHOLOGY: NON-NEOPLASTIC
Heart muscle, stomach, spleen, small intestine, bladder, thyroid, and adrenal gland exhibited only minor and insignificant changes. In lungs, liver, and kidneys, pathologic changes were observed frequently. The lesions of the lungs were for the most part typical of the chronic rat pneumonia described by Saxton et al. (1941) and others in old rats. The principal finding in the liver was fatty infiltration, usually diffuse in distribution; occasionally necrosis of the hepatic cells surrounding a central vein was seen. Chronic nephrosis were found in some rats. These lesions also were as described by Saxton et al. (1941) in old rats.

Effect levels

Dose descriptor:

NOAEL

Effect level:

6 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: no treatment-related effects were observed.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1: Hematologic findings

% test substance in diet	Erythrocytes x 10^6/Cu. Mm.	Hemoglobin g/100 mL	Leucocytes x 10^6/Cu. Mm.
0.00	7.4 ± 0.5	14.8 ± 0.8	7.8 ± 1.2
1.25	7.2 ± 0.5	14.2 ± 0.9	8.1 ± 1.9
6.25	7.6 ± 0.7	14.2 ± 1.4	7.9 ± 1.3

% test substance in diet	Leucocytes (%)
	Neutrophiles			Lymphocytes	Monocytes	Eosinophiles
	Non-segmented	Segmented	Total
0.00	1.0	23.6	24.6	71.0	3.1	1.4
1.25	1.2	24.6	25.8	70.2	2.5	1.5
6.25	1.3	23.1	24.4	72.5	2.4	0.8

Table 2: Incidences of pathologic lesions at necropsy

% test substance in diet	Number of rats subjected to necropsy	Number of rats affected
		Gross pathologic lesions
		None	Pneumonitis	Renal Disease	Preputial gland infection	Ear infection	Arteritis	Tumors, all types	Other
0.00	16	3	9	6	3	1	1	2	3
1.25	15	2	7	4	3	1	1	0	1
6.25	16	3	6	7	5	3	3	2	2