Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 Jan - 21 Feb 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-Ethylhexyl benzoate
- Physical state: clear colourless liquid
- Analytical purity: 99.734%
- Impurities (identity and concentrations): 2-Ethyl-4-methyl-1-pentyl benzoate 0.209%, C8 benzoate 0.023%, 2-Ethylhexyl phthalate 0.004%, unknown impurities 0.03%
- Lot/batch No.: 9915-133-2
- Sample ID: 9915-140-2
- Expiration date of the lot/batch: 2000-12-04
- Storage condition of test material: room temperature in light, in brown glass bottle

Test animals

Species:
rat
Strain:
other: Hsd:Sprague-Dawley (CD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd., Bicester, Oxon, UK
- Age at study initiation: 8-11 weeks
- Weight at study initiation: 201-307 g
- Fasting period before study: animals were fasted overnight prior to administration.
- Housing: animals were housed in groups of up to three animals of the same sex in metal cages with mesh floors.
- Diet: standard laboratory rodent diet (Special Diet Services RMI(E) SQC expanded pellet), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 24-52
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: aqueous methyl cellulose (1% w/v)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 and 25% (w/v)
- Amount of vehicle (if gavage): 20 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: The dose level was chosen in compliance with the guidelines.
Doses:
2000 and 5000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality was checked at least twice daily, animals were checked for clinical signs soon after dosing and at frequent intervals for the remainder of Day 1. Subsequently, animals were observed once in the morning and again at the end of the experimental day. Bodyweight was recorded at Day 1, 8 and 15 and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off according to OECD 423
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: experimental value
Mortality:
2000 mg/kg bw: 1/3 females (at 72 h post-dose) and 0/3 males died
5000 mg/kg bw: 1/3 females (at 48 h post-dose) and 2/3 males (at 48 h post-dose) died
Clinical signs:
Clinical signs of reaction of treatment comprised abnormal gait and hunched posture, seen in all rats at both dosages. In addition, lethargy, reduced body temperature, piloerection, loose faeces, partially closed eyelids, dull eyes, reduced body tone, prostration, shallow respiration, pallor of the skin and staining from urine were seen in one or more rats during the study.
Recovery of surviving rats, as judged by external appearance and behaviour, was complete by Day 3.
Body weight:
A reduced body weight gain was observed in one female (2000 mg/kg bw) on Day 8. In all other animals no effect on body weight was noted.
Gross pathology:
Necropsy revealed no substance-related findings.

Any other information on results incl. tables

Table 1. Table for acute oral toxicity.

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

5000

2/3/3

 - Day 3

Day 2 

66

2000

0/3/3

 - Day 3

-

0

Females

5000

1/3/3

 - Day 3

Day 2 

33

2000

1/3/3

 - Day 3

Day 3

33

LD50 = 2500 mg/kg bw (cut off value OECD 423)
LD50 = 5000 mg/kg bw (experimental value)

* first number = number of dead animals

 second number = number of animals with clinical signs

 third number = number of animals used

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified