Benzyl 4-[(1-butyl-5-cyano-1,6-dihydro-2-hydroxy-4-methyl-6-oxopyridin-3-yl)azo]benzoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 July to 13 August, 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Disperse Yellow 231

IUPAC Name:

Disperse Yellow 231

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna (UK) Limited, Wyton, Huntingdon, Cambridgeshire, UK
- Age at study initiation: 5 to 8 weeks old
- Weight at study initiation: males: 125 - 150 g; females: 122 - 150 g
- Fasting period before study: overnight until 2 hours after dosing
- Housing: groups of 5 by sex in solid floor polypropylene cages with sawdust bedding
- Diet: ad libitum; Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, UK
- Water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 22 °C
- Relative humidity: 65 - 70 %
- Air changes: 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12, controlled by a time switch

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

- Preparation: the test item was ground to a fine powder using a mortar and pestle and freshly prepared as required at the appropriate concentrations in distilled water. Identification and stability of the test item were not determined.
- Administration: oral gavage using a metal cannula attached to a graduated syringe

Doses:

- Dose volume: 10 ml/kg based on fasted body weight at dosing
- Dosage of range-finding study: 2000 and 5000 mg/kg bw
- Dosage of main study: 5000 mg/kg bw

No. of animals per sex per dose:

- Range-finding study: 1 male and 1 female per dose (two doses studied; total = 4 animals)
- Main study: 5 males and 5 females (total = 10 animals)

Control animals:

no

Details on study design:

RANGE-FINDING STUDY
- Duration of observation period following administration: 5 days
- Observations: mortality and overt toxicity
- Frequency of observations: 1 and 4 hours after administration, then daily up to 5 days
- Necropsy of survivors performed: no

MAIN STUDY
- Duration of observation period following administration: 14 days
- Observations: mortality, overt toxicity, clinical observations, bodyweight, post-mortem examination
- Frequency of observations: 1 and 4 hours after administration, then daily up to 5 days
- Frequency of weighing: days 0, 7 and 14
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

For the five days following oral administration, no mortality was observed at either dose. Using the mortality data, the LD50 of the test item was predicted to be greater than 5000 mg/kg bw, hence this dose was selected for the main study.
The high-dose and low-dose males both demonstrated hunched posture, lethargy, piloerection and decreased respiratory rate at 1 hour post dosing, and the high-dose and low-dose females both demonstrated hunched posture and piloerection at this time point.
All four animals continued to demonstrate hunched posture and piloerection at four hours after administration; no symptoms were observed at 24 hours after adminstration until the end of the test.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed among either male or female rats at the dose tested.

Clinical signs:

No signs of systemic toxicity were noted during the study period.

Body weight:

All animals showed expected gains in bodyweight over the study period.

Gross pathology:

No abnormalities were noted at necropsy of animals killed at the end of the study period.

Applicant's summary and conclusion

Interpretation of results:

other: not classified according to the CLP Regulation (EC 1272/2008)

Conclusions:

The LD50 of test item to male and female rats was found to be greater than 5000 mg/kg bw.

Executive summary:

The acute oral toxicity of the test item to male and female Sprague-Dawley rats was evaluated in an experimental study according to the OECD guideline 401 (1981). In a preliminary dose-range finding study, one male and one female were administered 5000 mg/kg bw by oral gavage, and additionally one male and one female were administered 2000 mg/kg bw. All four animals were monitored for mortality and overt toxicity for 5 days (1 and 4 hours then daily). No mortality/overt toxicity was observed, hence the higher dose was selected for the main study.

In the main study, 5 males and 5 females were dosed 5000 mg/kg bw and monitored for mortality and clinical signs at 1 and 4 hours then daily until 14 days, after which time all surviving animals were sacrificed and subjected to necropsy. Body weights were monitored on test days 0, 7 and 14. No mortality occurred; based on mortality, the LD₅₀ value for the test item was found to be greater than 5000 mg/kg bw. No clinical signs, unexpected bodyweight changes or abnormal necropsy findings were noted.