Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 4 April 2000 to 31 May 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study to GLP

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Hostaphat B 310 roh (Tributoxyethyl phosphate, TBEP)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan winkelmann, Borchen
- Age at study initiation: 6-10 weeks
- Weight at study initiation: male: 204-225 g; female: 172-190 g
- Fasting period before study: about 16 hours
- Housing: air-conditioned rooms in macrolon cages (type 4) on soft wood granulate in groups of 5
- Diet (e.g. ad libitum): ssnif R/M-H (V 1534) ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 4 April 2000 To: 18 April 2000

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% emulsion
- Amount of vehicle (if gavage) : 10 ml/kg bw
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): n/a
- Purity: n/a
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing: observations twice daily; weighing weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights
Statistics:
Not required

Results and discussion

Preliminary study:
No deaths at 500, 1000 or 2000 mg/kg bw in 1 animal per sex per dose level
Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Mortality:
None
Clinical signs:
Males & females: Decreased spontaneous activity, irregular respiration, stilted and uncoordinated gait.
Females: stupor, panting, bristled coat, sunken flanks, ataxic gait, forward crawling, lateral/prone position, no righting reaction, twitching, squatting posture, dilated pupils.
All clinical signs has resolved by day 4.
Body weight:
No effect
Gross pathology:
No macroscopically visible changes

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 of TBEP in Sprague-Dawley rats was greater than 2000 mg/kg bodyweight for males and females.
TBEP is not classified for oral toxicity according to the criteria of Annex VI Directive 67/748/EEC or EU GHS.
Executive summary:

The test article, Hostaphat B 310 roh (Tributoxyethyl phosphate, TBEP) was evaluated for acute oral toxicity in groups of 5 male and 5 female Sprague-Dawley rats. The test article was administered as an emulsion in water at a single dose of 2000 mg/kg bw by gavage. Observations were made on each animal for mortality and clinical signs at 10, 30 and 60 minutes, 2, 4, 8 and 24 hours after dosing and twice daily for the rest of the 14 day observation period. At the end of the 14 day observation period, each animal was sacrificed and a gross necropsy was performed. No deaths were seen in males or females. There was no effect on bodyweight gain. Clincal signs reported in males and females were decreased spontaneous activity, irregular respiration, stilted and uncoordinated gait. In addition, stupor, panting, bristled coat, sunken flanks, ataxic gait, forward crawling, lateral/prone position, no righting reaction, twitching, squatting posture and dilated pupils were reported in females only. All clinical signs has resolved by day 4. There were no macroscopically visible changes at necropsy.

The oral LD50 was greater than 2000 mg/kg bw.

TBEP is not classified for oral toxicity according to the criteria of Annex VI Directive 67/748/EECor EU GHS.