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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:
25 February 1997 - 25 March 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD, EC, EPA, and Japanese test guidelines, and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan Ministry of International Trade and Industry (MITI), Directive, concerning the conduct of acute toxicity studies
Deviations:
no
Qualifier:
according to
Guideline:
other: EPA Pesticide Assessment Guidelines, Subdivision F. Hazard Evaluation: Human and Domestic Animals 81-1 Acute oral toxicity study (Revised Edition November 1984). Subdivision F provides detailed information relating to data requirements of 40 CFR Part 158.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Benzoflex 2-45 Diethylene glycol dibenzoate (DEGDB)
- Physical state: Clear colourless liquid
- Analytical purity: Diethylene glycol dibenzoate - 89.9% (w/w)
- Impurities (identity and concentrations):
Diethylene glycol monobenzoate - 5.85% (w/w)
Dipropylene glycol dibenzoate - 1.50% (w/w)
Ethylene glycol dibenzoate - 0.19% (w/w)
Triethylene glycol dibenzoate - 0.15% (w/w)
Unidentified component 1 - 0.10% (w/w)
Unidentified component 2 - 0.10% (w/w)
Unidentified component 3 - 0.54% (w/w)
- Lot/batch No.: 56625030
- Expiration date of the lot/batch: 19 May 1998
- Storage condition of test material: Room temperature.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: approximately 7 to 10 weeks
- Weight at study initiation: 201 to 231 g
- Fasting period before study: Animals were fasted overnight before dosing and for approximately 4 hours after dosing.
- Housing: Housed in groups of up to five rats of the same sex in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): Standard laboratory rodent diet provided ad libitum
- Water (e.g. ad libitum): Drinking water was provided ad libitum.
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 23°C
- Humidity (%): 38 - 57 % RH
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours light per 24 hour period


IN-LIFE DATES: From: 25 February 1997 To: 25 March 1997

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not applicable - administered as supplied by sponsor.


MAXIMUM DOSE VOLUME APPLIED: 4.270 mL/kg (5000 mg/kg group)


Doses:
3200 mg/kg (Preliminary test, one animal per sex)
5000, 2000, and 3200 mg/kg (main test groups - 5 animals per sex per group).
No. of animals per sex per dose:
5 (Main test groups)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations (clinical signs) taken frequently on day of dosing then twice daily for remainder of
observation period. Bodyweights recorded on days 1 (day of dosing), 8, and 15, or on death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic pathology.
Statistics:
The acute median lethal oral dose (LD50) to male and female rats was calculated using the method of Finney [FINNEY, D.J. (1971) Probit Analysis, 3rd ed., Cambridge University Press, Cambridge]

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
4 843 mg/kg bw
95% CL:
4 198 - 5 588
Sex:
female
Dose descriptor:
LD50
Effect level:
3 535 mg/kg bw
95% CL:
2 892 - 4 322
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 190 mg/kg bw
95% CL:
3 504 - 5 072
Mortality:
One female at 3200 mg/kg and three males and all females at 5000 mg/kg died during the study. All deaths occurred within five days of dosing.
Clinical signs:
Refer to full list of clinical signs in "Remarks on results" section, below.
Body weight:
A slightly low bodyweight gain was recorded on Day 15 for one female at 2000 mg/kg and for one further female at 3200 mg/kg. All other surviving rats were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were observed among animals surviving treatment and killed at study termination on Day 15.
The gross pathological examination of the animals which died were:
3200 mg/kg (one female): Congestion (characterised by prominent blood vessels) in the brain and gaseous distension in the stomach and along the alimentary tract.
5000 mg/kg (three males and all (five) females): Congestion (characterised by dark appearance / prominent blood vessels / inflammation) in brain, heart, lungs, liver, spleen and kidneys. Congestion or pallor with fluid contents, gaseous distension and black patches were also seen in the stomach and along the alimentary tract.

Any other information on results incl. tables

Piloerection was observed in all rats within eight minutes of dosing. This sign persisted and was accompanied in rats later during the study by:

- hunched posture, waddling unsteady gait, lethargy and ungroomed appearance, in all rats at all dosages

- respiratory distress (characterised by increased / decreased / gasping or noisy respiration in all rats at 2000 mg/kg all males and four females at 3200 mg/kg and three males and all females at 5000 mg/kg

- pallid etremities in all females at 2000 mg/kg and all rats at 3200 and 5000 mg/kg

- increased salivation in one male at 2000 mg/kg four females at 3200 mg/kg and all males and four females at 5000 mg/kg

- walking on toes in all rats at 2000 and 5000 mg/kg and all males and four females at 3200 mg/kg

- increased lacrimation in one female at 2000 and 3200 mg/kg and all males and two females at 5000 mg/kg

- body tremors in one male and one female at 2000 mg/kg four females at 3200 mg/kg and all males and two females at 5000 mg/kg

- cold body surfaces in all males at 2000 mg/kg and in all rats at 3200 and 5000 mg/kg

- sensitivity to handling in one male and all females at 2000 mg/kg all rats at 3200 mg/kg and four males and two females at 5000 mg/kg

- partially closed eyelids in two females at 3200 mg/kg and in all rats at 5000 mg/kg

- faecal disturbances (characterised by soft to liquid or lack of faeces) in all females at 2000 mg/kg and in two males at 5000 mg/kg

- clonic convulsions in four males at 5000 mg/kg

- hyperactivity in one male at 5000 mg/kg

- prostration in one female at 3200 mg/kg and four males and two females at 5000 mg/kg

- stained muzzle and lor urogenital area in two females at 2000 mg/kg in all rats at 3200 mg/kg and in four males and two females at 5000 mg/kg

- thin appearance in one female at 3200 mg/kg and one male at 5000 mg/kg

- straub tail in two males at 5000 mg/kg

Recovery of surviving rats was complete with the exception of piloerection and unsteadiness in males at 5000 mg/kg by either Day 10 (3200 mg/kg) Day 11 (2000 mg/kg) or Day 13 males 5000 mg/kg

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information According to Directive 67/548/EEC Criteria used for interpretation of results: EU
Conclusions:
The acute median lethal oral dose (LD50) and 95% confidence limits to male and female rats of DEGDB were calculated to be:
Males only: 4843 (4198 to 5588) mg/kg bodyweight
Females only: 3535 (2892 to 4322) mg/kg bodyweight
Combined sexes: 4190 (3504 to 5072) mg/kg bodyweight.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material DEGDB when administered to rats. The study was conducted according to OECD, EC, US EPA, and Japanese (MITI) test guidelines, and in compliance with GLP.

In the definitive test, ten rats (five male and five female) in each treatment group were dosed at 5000, 3200, or 2000 mg/kg bodyweight, by oral gavage. Observations were taken for 14 days following dosing, and macroscopic pathology was performed on all animals.

The acute median lethal oral doses (LD50) to male and female rats of DEGDB were calculated to be: 4843 mg/kg bodyweight (males), 3535 mg/kg bodyweight (females), and 4190 mg/kg bodyweight (both sexes).