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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:
October 9th - November 9th, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. certificate)
Remarks:
issued 31JAN1994
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
Physical appearance: colourless viscous liquid
Storage conditions: At room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK)
- Age at study initiation: 5-8 weeks
- Weight at study initiation: males 137 - 181g; females 132 - 154g
- Fasting period before study: o/n before dosing and 2 hours after dosing
- Housing: group-housed (up to 5 of same sex)
- Diet: ad libitum (Rat and mouse expanded diet No.1, special diets services limited, Witham, Essex, UK)
- Water: ad libitum
- Acclimation period: minimal 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 44-57
- Air changes (per hr): appr. 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.86 ml/kg
Doses:
500, 1000, 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
- Frequency of observations and weighing: Animals were observed for deaths 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded on the day of dosing and on days 7 and 14.
- Necropsy of survivors performed: yes (gross pathology)
- Other examinations performed: clinical signs, at 0.5, 1, 2 and 4 hours after dosing and subsequently once daily.
Statistics:
The LD50-value was calculated using a probit method of Finney, DJ: "Probit Analysis", 1971, Cambridge University Press. The LD50 and 95% confidence limits were calculated for males only.

Results and discussion

Preliminary study:
No mortality was observed in the range-finding study.
Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
619 mg/kg bw
Based on:
test mat.
95% CL:
>= 305 - <= 1 256
Remarks on result:
other: Male animals were considered to be more sensitive to the test material than female animals.
Mortality:
At 2000 mg/kg bw, all males died and 3/5 females.
At 1000 mg/kg bw, 3/5 males died (only males treated) and at 500 mg/kg bw 2/5 males died (at these dosages, only males were treated).
Mortality occurred within half an hour after dosing.
Clinical signs:
Common signs of systemic toxicity noted in the surviving animals were hunched posture, decreased respiratory rate and laboured respiration with additional signs of ataxia. Lethargy was commonly noted in males treated with 1000 mg/kg and females treated with 2000 mg/kg bw. Isolated incidents of systemic toxicity noted in two females treated with 2000 mg/kg bw were pilo-erection and/or pallor of the extremities.
Clinical signs disappeared one or two days after dosing in the surviving animals.
Body weight:
Surviving animals showed expected gain in body weight during the study.
Gross pathology:
Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Cat. 4 according to EC Regulation 1272/2008
Conclusions:
In an acute oral toxicity test performed according to the OECD guideline, the LD50 of BISOMER PTE was found to be 619 mg/kg bw.
Executive summary:

An acute oral toxicity test was performed according to the OECD guideline, with male and female rats.

At the starting dose (2000 mg/kg bw) all males and 3/5 females died. At the lower doses only males were treated. At 1000 mg/kg bw 3/5 rats died, at 500 mg/kg bw 2/5 rats died. Death occurred in all animals within 0.5 hours after dosing. The surviving animals showed hunched posture, decreased respiratory rate and laboured respiration with additional signs of ataxia. Lethargy was commonly noted in males treated with 1000 mg/kg and females treated with 2000 mg/kg bw. These clinical signs disappeared within one or two days after exposure. Surviving animals showed expected gain in body weight during the study. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Based on an LD50 of 619 mg/kg bw, BISOMER PTE is classified for acute oral toxicity cat. 4 according to EC regulation No 1272/2008.