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Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication meeting basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Effects of structured medium- and long-chain triacylglycerols in diets with various levels of fat on body fat accumulation in rats
Author:
Matsuo, T. and Takeuchi, H.
Year:
2004
Bibliographic source:
British Journal of Nutrition 91, 219¿225

Materials and methods

Principles of method if other than guideline:
The effects of structured medium- and long-chain triacylglycerols (MLCT) in diets containing 50¿200 g fat/kg on body fat accumulation were compared with those of long-chain triacylglycerols (LCT) in rats. The diets were fed to groups of 6 young adult male Wistar rats for 56 days.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
medium- and long-chain triacylglycerols
IUPAC Name:
medium- and long-chain triacylglycerols
Details on test material:
- Name of test material (as cited in study report): medium- and long-chain triacylglycerols (MLCT)
- Name of test material (as cited in study report): long-chain triacylglycerols (soybean-oil)
Soybean oil was used as the source of LCT, and was purchased from Nacalai Tesque, Inc. (Kyoto, Japan).
MLCT were prepared by transesterification of 200 g MCT and 800 g rapeseed oil, which were purchased from Nisshin Oil Mills (Tokyo, Japan).

Composition of fatty acids and triacylglycerols of the test oils:
- LCT contained (g/100 g total fatty acids): linoleic acid 53, oleic acid 24, alpha-linolenic acid 8
- MLCT contained (g/100 g total fatty acids): oleic acid 50, linoleic acid 16, caprylic acid 14, capric acid 5

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Japan SLC, Inc., Shizuoka, Japan
- Age at study initiation: 4 weeks
- Diet (ad libitum): CE-2 (CLEA Japan, Tokyo, Japan), a commercial rodent diet from age of 3 weeks to age of 4 weeks
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24+/-1
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: feed
Details on oral exposure:
Half of the groups were fed diets containing LCT, and the other half were fed diets containing MLCT.
Duration of treatment / exposure:
56 days
Frequency of treatment:
oral feeding study
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
50, 100, 150 and 200 g/kg food (5, 10, 15 and 20%)
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
5, 10, 15 and 20 g/kg bw/day
Basis:
other: assuming a daily food consumption of 100 g/kg bw/day according to OECD ENV/JM/MONO(2000)18 for young rats
No. of animals per sex per dose:
6
Control animals:
no

Examinations

Observations and examinations performed and frequency:
On the final day, rats in each dietary group were fasted for 12 h, then killed by decapitation.
Blood was collected to obtain serum; liver and intra-abdominal adipose tissues (epididymal, perirenal and mesenteric) were quickly removed, weighed, and stored until analyses. Carcass samples were obtained by removing the head, tail and splanchnic tissues, and were stored at until analysis of carcass composition.

CAGE SIDE OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: daily

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

FOOD EFFICIENCY:
Yes

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: Yes
- Parameters: serum glucose and triacylglycerols, serum insulin; further: liver total lipid, liver triacylglycerol concentrations, carcass fat and protein, hepatic capacities of citrate synthase and cytochrome oxidase

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes; at the end of the study, the rats were killed by decapitation, blood was collected to obtain serum, with the liver and intraabdominal adipose (epididymal, perirenal and mesenteric) tissues removed, weighed and stored at -40°C until analysis.
HISTOPATHOLOGY: No
Statistics:
All data were analysed by a factorial ANOVA and post hoc Scheffe¿s test. Differences were considered statistically significant at p<0.05.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
no adverse effects
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
no adverse effects
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:
effects observed, treatment-related
Description (incidence and severity):
no adverse effects
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
No adverse effects were noted in this study.

CLINICAL SIGNS AND MORTALITY
No effects observed.

BODY WEIGHT AND WEIGHT GAIN
In the LCT groups, final body weight and weight gain were significantly lower in rats fed 50 and 100 g fat/kg diet than in rats fed 150 and 200 g fat/kg diet. In the 150 and 200 g fat/kg diets groups, final body weight and weight gain were significantly lower in the MLCT groups than in the LCT groups

FOOD CONSUMPTION AND FOOD EFFICIENCY
Food intake was more suppressed by the feeding of a high-fat diet, and food efficiency increased significantly with increasing dietary fat both in the LCT and MLCT groups. In the 150 and 200 g fat/kg diet groups, food efficiency was significantly lower in the MLCT groups.

CLINICAL CHEMISTRY
Serum triacylglycerol concentration was significantly higher (P<0.05) in MLCT-fed rats, when compared to LCT-fed rats.
Serum glucose and insulin concentrations were significantly lower in the 50 g fat/kg diet group than in 100, 150, and 200 g fat/kg diet groups in rats fed LCT and MLCT diets, but the MLCT groups were not significantly different from the corresponding LCT dose groups.
Hepatic capacities of the citrate synthase and cytochrome oxidase were significantly higher in rats fed MLCT, when compared to LCT-fed rats.

ORGAN WEIGHTS
Liver weight and triacylglycerol content were not influenced by the levels of LCT and MLCT.
Liver triacylglycerol content was significantly increased in rats fed the MLCT diet, when compared to rats fed the 20% LCT/kg diet.
Perirenal adipose tissue weight and intra-abdominal adipose tissue weight was significantly (P<0.05) lower in the 15 and 20% MLCT dose groups, when compared to the 15 and 20% LCT dose groups.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
ca. 20 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: based on clinical observations, body weight, food efficiency, liver weights and clinical serum chemistry.
Dose descriptor:
NOAEL
Effect level:
200 000 mg/kg diet
Based on:
test mat.
Sex:
male
Basis for effect level:
other: based on clinical observations, body weight, food efficiency, liver weights and clinical serum chemistry.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 2: Body weight, food intake and food efficiency in rats fed experimental diets

(Mean values for six rats per group)

 

Fat in experimental diets (g/kg)

50

100

150

200

Body weight (g)

 

 

 

 

initial

L

87

88

88

89

ML

88

88

88

88

final

L

273

275

293

297

ML

272

272

272

278

gain

L

186

187

205

208

ML

185

185

184

190

Food intake (g)

 

 

 

 

 

L

14.3

13.7

13.6

13.1

 

ML

14.7

13.8

12.9

12.5

Food efficiency (mg/g)

 

 

 

 

 

L

236

248

274

289

 

ML

229

245

259

276

 

Applicant's summary and conclusion