Reaction mass of dimethyl adipate and dimethyl glutarate and dimethyl succinate

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of 10 rats per concentration received the test item in feed for 14 consecutive days. An additional group of 10 rats served as controls and was fed standard chow only. All rats were weighed daily (weekends excluded) during the test period and observations for clinical signs were made at the same time. Food consumption for the test period was recorded. On day 14, 5 rats from each group were sacrificed. The remaining half of each group were weighed every other day and observed for a 14-day recovery period on standard feed without test item. All rats were examined grossly, selected tissues were weighed, and selected tissues and organs evaluated histologically.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of dimethyl adipate and dimethyl glutarate and dimethyl succinate

EC Number:

906-170-0

Molecular formula:

CH3CO2(CH2)nCO2CH3 Where n = 2, 3 and 4

IUPAC Name:

Reaction mass of dimethyl adipate and dimethyl glutarate and dimethyl succinate

Test material form:

other: liquid

Details on test material:

See information in the field "Confidential details on test material"

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The test material mixed with ground Purina Lab Chow (GPLC) was fed .

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 days of treatment. Half of the animals were observed for further 14 days without treatment.

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
10, 20, 50 g/kg feed
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
10000, 20000, 50000 ppm
Basis:
nominal in diet

No. of animals per sex per dose:

10 male animals per sex and dose

Control animals:

yes, plain diet

Details on study design:

- Post-exposure recovery period in satellite groups: 14 days

Positive control:

no positive control used

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: treatment phase: daily; recovery period: every other day

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: No

FOOD EFFICIENCY: No

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

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see table 1)
HISTOPATHOLOGY: Yes (see table 1)

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

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:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
No deaths occured during the study period.
No clinical signs other than initial and sporadic weight loss were observed.

BODY WEIGHT AND WEIGHT GAIN
The rate of body weight gain was reduced in rats fed either 20 or 50 g/kg feed. This reflects, at least in part, lower food intake by these rats. Upon return to the ground lab chow (control diet), test rats in these 2 groups gained slightly more weight than did the controls although the rats in the 50 g/kg feed group weighed approximately 7% less than controls at the end of the recovery period.

GROSS PATHOLOGY AND HISTOPATHOLOGY
No gross or microscopic pathologic changes that could be attributed to exposure of DBE were detected.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 2:Weight and Food Consumption Data

Dose [ppm]	Dose [g/kg feed]	Average initial weight [g]	Average weight, day 14 [g]	Average weight, after 14 day recovery [g]	Average food consumption during test period [g/day/rat]	Estimated test item uptake [mg/kg bw/day] ^a)
0 (control)	0 (control)	244	329	391	26	-
10’000	10	245	325	401	24	980
20’000	20	239	302	394	22	1841
50’000	50	240	290	364	19	3958

^a) Estimation based on average food consumption and average initial body weight

Applicant's summary and conclusion

Conclusions:

Except for the observed slight weight gain effects, under the conditions of this test, DBE appeared to be devoid of general toxicity in this 14-day feeding study.

Executive summary:

Dibasic Esters (DBE) has been tested in a 14-day oral toxicity study on Crl:CD rats.

Groups of 10 male rats received feed containing DBE at concentrations of 0 (control), 10’000, 20’000, or 50’000 ppm for 14 consecutive days. All rats were weighed daily during the test period and observations for clinical signs were made at the same time. Food consumption for the test period was recorded. On the 14th test day, half of the rats of each test group were sacrificed. The remaining half of each group were weighed every other day, observed for a 14-day recovery period, and sacrificed 14 days later. All rats were examined grossly, selected tissues were weighed, and selected tissues and organs evaluated histologically.

Oral administration of DBE to rats over 14 days produced no deaths. No gross or microscopic pathologic changes that could be attributed to exposure of DBE were detected. No clinical signs other than initial and sporadic weight loss were observed. The rate of body weight gain was reduced in rats of the mid- and high-dose group which is reflected, at least in part, by lower food intake by these rats. During the recovery period, test rats in these 2 groups gained slightly more weight than the controls although the high-dose rats weighed approximately 7% less at the end of the recovery period.

Except for the observed slight weight gain effects, under the conditions of this test, DBE appeared to be devoid of general toxicity in this 14-day feeding study.