2',3-bis[[3-[3,5-di-tert-butyl-4-hydroxyphenyl]propionyl]]propionohydrazide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 Feb - 5 Mar 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(adopted 1981)

GLP compliance:

yes

Remarks:

A statement of the Quality Assurance Unit was added.

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2',3-bis[[3-[3,5-di-tert-butyl-4-hydroxyphenyl]propionyl]]propionohydrazide

EC Number:

251-156-3

EC Name:

2',3-bis[[3-[3,5-di-tert-butyl-4-hydroxyphenyl]propionyl]]propionohydrazide

Cas Number:

32687-78-8

Molecular formula:

C34H52N2O4

IUPAC Name:

3-(3,5-di-tert-butyl-4-hydroxyphenyl)-N'-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoyl]propanehydrazide

Details on test material:

Purity: 99.1%
Physical appearance: solid

Test animals

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7-8 weeks
- Weight at study initiation: males: 176-204 g; females: 180-197 g
- Fasting period before study: Fasted overnight
- Housing: 5 animals per Makrolon cage (type 3)
- Diet (ad libitum): NAFAG, Gossau SG
- Water: ad libitum
- Acclimation period: at least 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-10
- Photoperiod (hrs dark / hrs light): 10 h light day

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG400

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 20 mL/kg bw


DOSAGE PREPARATION:
Test substance was suspended to achieve the corresponding dosage level. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Doses:

4000, 5000, 6000, 7000 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
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight (prior to treatment, day 7, day 14)

Statistics:

LD50 including 95% confidence limits are calculated by the logit model.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 7 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred.

Mortality:

No mortality occurred.

Clinical signs:

other: 4000 mg/kg bw: dyspnoea (slight, until day 6), exophthalmus (slight, until day 3), ruffled fur (moderate 1-5 h, slight until day 7), diarrhoea (slight 1-5 h), body position curved (slight until day 4) 5000 mg/kg bw: sedation (slight 1-3 h), dyspnoea (slig

Gross pathology:

No substance related gross organ changes were seen.

Any other information on results incl. tables

Table 1: Mean body weight of male and female rats [g] at day 1, 7, and 14.

Mean body weight [g] ± sd	4000 mg/kg bw	5000 mg/kg bw	6000 mg/kg bw	7000 mg/kg bw
Day 1 male	204±10	176±11	201±19	186±18
Day 1 female	192±10	180±12	197±21	188±8
Day 7 male	245±9	234±10	248±11	230±9
Day 7 female	219±10	204±16	201±14	202±5
Day 14 male	291±21	284±10	288±9	284±10
Day 14 female	223±20	217±25	224±20	216±4

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 in the rat is greater than 7000 mg/kg body weight.

Executive summary:

In an acute oral toxicity study five male and five female Tif: RAIf (SPF) rats were treated with test substance in PEG at dose levels of 4000, 5000, 6000, and 7000 mg/kg by gavage. Within the observation period of 14 days dyspnoea, exophthalmus, ruffled fur, diarrhoea, and curved body position have been observed, which were reversible within the observation period. No mortality occurred. No substance related gross organ changes were seen. Based on the results of this study, an LD50 of > 7000 mg/kg bodyweight was derived.