Tris-(2-hydroxy-4-heteropolycycle-carboxylato-O´O) salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-04-13 to 1994-05-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987-02-24

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 1994-03-16

Test type:

standard acute method

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

solid: particulate/powder

Details on test material:

- State of aggregation: cream coloured powder

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan U.K. Ltd., Blackthorn, Bicester, Oxon, U.K.
- Age at study initiation: approx. 5 to 8 weeks old
- Weight at study initiation: males: 134 - 146 g, females: 127 - 135 g
- Fasting period: overnight fast immediately before dosing and for approx. tow hours after dosing
- Housing: housed in groups up to 5 by sex in solid floor polypropylene cages furnished with woodflakes
- Diet (ad libitum; except fasting period): Rat and Mouse Expanded Diet No. 1
- Water (ad libitum; except fasting period): mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 23 °C
- Relative humidity: 46 - 56 %
- Air changes: approx. 15/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

B. P.

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL / kg

The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.

DOSAGE PREPARATION:
The test material was freshly prepared as a suspension at the appropriate concentration in arachis oil B.P. Homogeneity was assured by the use of a Silverson homogeniser.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males / 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- death and overt signs of toxicity: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- body weights: prior to dosing on day 0 as well as on days 7 and 14
- Necropsy of survivors performed: yes, gross pathological examination

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Results and discussion

Preliminary study:

A range-finding study was conducted in rats (1 male / 1 female) at each dose level of 1000 and 2000 mg/kg. Death and overt signs of toxicity were recorded 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 5 days. Individual body weights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.
There were no deaths. Signs of systemic toxicity noted were hunched posture and decreased respiratory rate, which were observed in the females of the 1000 and 2000 mg/kg dose levels..
Based on this results, a dose level of 2000 mg/kg bw was selected for the main study.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

Incidents of systemic toxicity noted were hunched posture (3/5 males), lethargy (1/5 males) and ptosis (1/5 males). The males had recovered one day after dosing.

Body weight:

All animals showed expected body weight gain during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (male and female rats) > 2000 mg/kg bw.
According to the Regulation (EC) 1272/2008 and subsequent adaptions, the substance is not acutely toxic via the oral route.