Registration Dossier

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
Study period:
1981
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
See information in the field "Confidential details on test material"

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male
Details on test animals and environmental conditions:
Young adult animals were used for this study

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
Details on analytical verification of doses or concentrations:
not applicable
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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
10, 20, 50 g/kg feed
Basis:
nominal in diet
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)
Other examinations:
None
Statistics:
Standard statistical methods were used

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

-

10000

10

245

325

401

24

980

20000

20

239

302

394

22

1841

50000

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, Dibasic esters 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), 10000, 20000, or 50000 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.