3-(3-tert-butyl-4-hydroxyphenyl)propionic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Feb. 8, 1988 to Apr. 25, 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, according to accepted guideline, with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(3-tert-butyl-4-hydroxyphenyl)propionic acid

EC Number:

403-920-4

EC Name:

3-(3-tert-butyl-4-hydroxyphenyl)propionic acid

Cas Number:

107551-67-7

Molecular formula:

C13H18O3

IUPAC Name:

3-(3-tert-butyl-4-hydroxyphenyl)propanoic acid

Test animals

Species:

rat

Strain:

other: Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Ltd. (Animal Production)
- Age at study initiation: 7 to 8 weeks.
- Weight at study initiation: 176 to 228 g.
- Fasting period before study: Prior to dosing, the animals were fasted overnight.
- Housing: Segregated by sex, group housed (5 animals/cage) in Macrolon cages type 4, with standardized soft wood bedding.
- Diet (e.g. ad libitum): Rat chow, ad libitum.
- Water (e.g. ad libitum): Water, ad libitum.
- Acclimation period: At least 5 days before administration.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2°C.
- Humidity (%): 55±10%.
- Air changes (per hr): 15 air change per hr.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500, 1000, and 2000 mg/kg body weight.
- Amount of vehicle (if gavage): 10 mL/kg body weight.


MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg body weight.

Doses:

500, 1000, and 2000 mg/kg body weight.

No. of animals per sex per dose:

500 mg/kg body weight group: 5 males/group
1000 mg/kg body weight group: 5/sex/group
2000 mg/kg body weight group: 5 females/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days
Signs and symptoms: Daily.
Body weight: At start and on Days 7, 14, and at death.
Necropsies: Spontaneously dying animals were submitted to a gross necropsy as soon as possible
- Necropsy of survivors performed: Yes.

Statistics:

From the body weights, the group means and their standard deviations were calculated.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 000 - 2 000 mg/kg bw

Mortality:

See Table 1.

Clinical signs:

other: Ruffled fur, dyspnea, hunched posture, and exophthalmos were seen, being common symptoms in acute tests. Additionally, slightly to severely reduced spontaneous activity was observed in the spontaneously died animals dosed with 2000 mg/kg bw. The surviving

Gross pathology:

At autopsy, a spotted thymus was observed in one female given 1000 and in four females given 2000 mg/kg bw.
Edematous lungs were found in one female and a liquid-filled thoracic cavity in three females of the 2000 mg/kg bw dose group, respectively.

Other findings:

Not available.

Any other information on results incl. tables

Table 1. Rate of Deaths

Dose mg/kg	Totals			Time of Death
	In group	Deaths	Deaths	Hours after treatment				Days of Post-exposure Period
		No.	%	1	2	3	5	1	2	3	4	5	6	7	8	9	10	11	12	13	>14
Males
500	5	0	0
1000	5	0	0
Females
1000	5	0	0
2000	5	5	100					2	2	1

Table 2. Signs and Symptoms

Observation

Exposure day: hours

Days of post-exposure period

1

2

3

5

1

2

3

4

5

6

7

8

9

10

11

12

13

>13

500 mg/kg males

ruffled fur

XX

XX

XX

XX

X

X

X

X

X

x

x

x

dyspnea

X

X

X

X

X

X

X

X

X

hunched post

X

X

X

X

X

X

1000 mg/kg males

ruffled fur

X

X

X

X

X

X

X

X

X

x

x

x

x

x

dyspnea

X

X

X

X

X

X

X

X

X

hunched post

X

X

X

X

X

1000 mg/kg females

ruffled fur

XX

XX

XX

XX

X

X

X

X

X

X

X

X

X

dyspnea

X

X

X

X

X

X

X

X

X

X

X

hunched post.

X

X

X

X

X

X

X

X

exophthalmos

X

2000 mg/kg females

ruffled fur

XX

XX

XX

XX

XX

X

dyspnea

X

X

X

X

X

X

hunched post.

X

X

X

X

X

ventr. lecuiib.

x*

x*

x*

x*

x*

X

red.spcn.act.

X

X

X

X

XX

XXX

X =- slight XX = moderate xxx = marked

hunched post. = hunched posture

ventr.recumb. = ventral recumbency

red.spcn.act. = reduced spontaneous activity

* = only in one animal

Table 3. Mean Body Weight and Standard Deviation

	Males			Females
Dose (mg/kg)	Day 1	Day 7	Day 14	Day 1	Day 7	Day 14
500	220/ 6.2	296/ 7.9	355/ 13.1	-	-	-
1000	211/7.3	261/ 10.7	322/ 18.7	185/ 5.5	215/ 7.5	235/ 5.5
2000	-	-		184/ 9.2	-	-

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Single oral application of the test item induced spontaneous death of all female animals in the high dose group (2000 mg/kg) until day 3 of the post observation period. Therefore LD50 is considered to be > 1000 mg/kg but < 2000 mg/kg bw.