NITTA

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 April to 27 May 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

liquid: viscous

Details on test material:

- Appearance: amber-coloured, slightly viscous liquid
- Storage conditions: 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: Interfauna (U.K.) Limited, Wyton, Huntingdon, Cambridgeshire
- Age at study initiation: ca. 5 - 8 weeks
- Weight at study initiation: males: 211 - 234 g; females: 161 - 181 g
- Fasting period before study: yes (overnight before dosing and ca. 2 hours after dosing)
- Housing: animals were housed in groups of up to 5 by sex in solid-floor polypropylene cages with sawdust bedding
- Diet: ad libitum (Rat and Mouse Expanded Diet No. 1, Special Diet Services Ltd)
- Water: ad libitum
- Acclimation period: 5 days (minimum)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22 °C
- Humidity (%): 55 - 68 %
- Air changes (per hr): ca. 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5.77 mg/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for mortality and overt signs of toxicity 1 and 4 hours after dosing and subsequently once daily for 14 days. Bodyweights were recorded on the day of dosing (day 0) and on days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

None of the animals died during the preliminary study and subsequently, the top dose of 5000 mg/kg bw was selected for the main study.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the animals died during the study period.

Clinical signs:

other: No signs of systemic toxicity were noted during the study period. All animals showed expected gains in bodyweight over the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study, the acute oral LD50 of the test material was determined to be in excess of 5000 mg/kg bw.

Executive summary:

The acute oral toxicity of the test material was evaluated in a study which was conducted under GLP conditions and in accordance with the standardised guidelines EU Method B.1 and OECD 401.

During the study, the test material was administered by oral gavage to one group of five male and five female Sprague-Dawley rats at 5000 mg/kg bw. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing. All animals were subject to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice on day 15.

None of the animals died during the study and no clinical signs were noted. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Furthermore, no abnormalities were found at macroscopic post mortem

examination of the animals.

Therefore, under the conditions of the study, the oral LD50 value of the test material in male and female Sprague-Dawley rats was in excess of 5000 mg/kg bw, the highest permissible dose level tested.