Registration Dossier

Diss Factsheets

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

Constituent 1
Chemical structure
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.