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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data considered reliable as copy of report received from the US EPA. Studies performed in accordance with 40 CFR part 716 for a chemical substance listed in Section 716.120 and processed for commercial purposes.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
According to Hagan, EC (1959) Acute Toxicity; Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, pp 17-25. Comparison with
OECD Test 401 suggests that with the exception of the absence of a control group and analysis of the formulations procedures and study design were similar to those prescribed in this guideline
GLP compliance:
not specified
Remarks:
GLP was just being introduced in 1978
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of test material (as cited in study report): 78-032-02. Report has been anotated manually to confirm that this matecode corresponds to diethyl phthalate

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Summit View Farm Belvidere New Jersey USA
- Age at study initiation: Not reported
- Weight at study initiation: 139-164 g
- Fasting period before study: overnight prior to dosing
- Housing: assumed to be 5 animals/sex/group
- Diet (e.g. ad libitum): Wayne Animal Feeds available ad libitum except for overnight fast prior to dosing
- Water (e.g. ad libitum): ad libitum with possible exception of overnight prior to administration of test item
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

IN-LIFE DATES: From: 16th March 1978To: 31st March 1978

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Test Item used as supplied
Doses:
0.5, 1.0, 2.0 and 5.0 mL/kg
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed for signs of pharmacologic activity and/or toxicitys 1, 3, 6 and 24 hours post dose and daily thereafter for a total of 14 days. Weighed on intitiation and termination of the study
- Necropsy of survivors performed: Yes
Statistics:
The LD50 was calculated, including the 95% confidence limits) where possible using the method of Litchfield and Wilcoxon (Litchfield JT and Wilcoxon F (1949) J Pharmacol. Exptl.Therap. pp96-99,

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 5 mL/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 and 95% limits not calculable
Mortality:
One male animal given 5 mL/kg was sacrificed due to moribund condition on Day 5. Only signs observed from 24 hours after reciving the test item until sacrifice were slight depression and 28 g weight loss. No gross abnormalities at necropsy reported.
Clinical signs:
No clinical signs were oberved with the exception of 1 male dosed at 5.0 mL/kg that appeared slightly depressed within 24 hours of dosing and continued to Day 5 when it was humanely killed from the study.
Body weight:
There were no effects on body weight which could definitely be attributed to treatment. Two males gained less weight than expected than their counterparts. One of these (dosed at 0.5 mL/kg) was found to have fibrous tissue encasing the heart and lungs at necropsy and may have had an existing condition or been mis-dosed. The other animal, dosed at 1.0 mL/kg, gained a similar amount but did not show any signs clinical signs or abnormalities at necropsy. The male dosed at 5.0 mL/kg sacrificed due to ill health on Day 5 lost 28 g in the 5 days between administration of the test item and sacrifice.
Gross pathology:
With the exception of one male (dosed at 0.5 mL/kg) that was found to have fibrous tissue encasing the heart and lungs at necropsy, no abnormalities were found at gross necropsy of animals surviving the 14 day observation period.
Other findings:
None reported

Any other information on results incl. tables

One male rat given 5 ml/kg was sacrificed on day 5 following mild depression and bodyweight loss. In the absence of similar effects in other animals given the same dose this death may not be due to the test item.

Dose Level              Sex              Dead/Dosed              %            

                                                       (ml/kg)              5M:5F              0/5:0/5                     0

                                                               0.5            5M:5F              0/5:0/5                     0

1.0             5M:5F              0/5:0/5                     0

2.0             5M:5F              0/5:0/5                     0

5.0             5M:5F              0/5:0/5                     10

Result       LD50: > 5.0 ml/kg

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 was found to be greater than 5.0 mL/kg.
Executive summary:

Acute toxicity following administration of a single oral dose has been investigated in the rat. The LD50 was found to be in excess of 5 mL/kg body weight. At a density of 1.1181 the administered dose of 5 mL/kg equates to 5591 mg/kg body weight.