4,4'-isopropylidenebis[2-allylphenol]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Date of acclimatization: 20 November 1985; Date of administration:27 November 1987 and 2 December 1985; Date of Completion: 16 December 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No GLP methodology followed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-isopropylidenebis[2-allylphenol]

EC Number:

217-121-1

EC Name:

4,4'-isopropylidenebis[2-allylphenol]

Cas Number:

1745-89-7

Molecular formula:

C21H24O2

IUPAC Name:

4-{1-[4-hydroxy-3-(prop-2-en-1-yl)phenyl]propyl}-2-(prop-2-en-1-yl)phenol

Test material form:

other: viscous liquid

Details on test material:

_ Identification: TK 11907
- Batch: Op. 1
- Generic: XU 292 B
- Storage conditions: Room temperature
- Description: Viscous liquid, insoluble in water
- Purity: Pilot-sample
- Test article: November 19, 1985

Test animals

Species:

rat

Strain:

other: Tif: RAIf (SPF), F3-hybrid of RII 1/Tif x RII 2/Tif

Sex:

male/female

Details on test animals or test system and environmental conditions:

Rationale
The rat has been selected for this test as being a Standard species for the determination of an acute oral LD50.

- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland.
- Initial Body Weight Range: 171 - 216 g
- Initial Age: 7-8 weeks
- Individual Identification: by colour code using picric acid
- Husbandry: The animals were kept under conventional laboratory conditions. They were caged in groups of 5 in Hacrolon cages type 4 with standardized soft wood bedding (Societe Parisienne des sciures, Pantin)
The animal room was air conditioned: temperature 22±3° C, relative humidity 55±15%, 12 hours light/day, approximately 15 air changes/h.

Diet: Rat food, NAFAG No. 890, NAFAG AG, Gossau, SG (Switzerland), and water were provided ad libitum.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Ol. Arachidis Ph. H. VI (Siegfried AG, Zofingen/Switzerland)

Details on oral exposure:

- Administration of the test article: One single dose, per os
- Volume (ml/kg body weight) applied: 10

Doses:

2000 and 5000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females per dose level (in total 20 animals)

Control animals:

no

Details on study design:

- Pretreatment: Prior to dosing, the animals were fasted overnight.
- 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: on days 1, 7, 14, and at death
- Necropsy of survivors performed: yes Spontaneously dying animals were submitted to a gross necropsy as soon as possible; survivors at the end of the observation period.

Statistics:

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

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 - < 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 5 females died (100%. 1 day 1 and 4 day 2 of post exposure)

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2 males died (40%: 1 day of post exposure period and day 6 post exposure).LD50 perhaps > 5000 mg/kg w

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 - < 5 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg bw: No mortality
At 5000 mg/kg bw: 2 males (40%: 1 day of post exposure period and day 6 post exposure)) and 5 females (100%. 1 day 1 and 4 day 2 of post exposure)

Clinical signs:

other: The surviving animals recovered within 6-12 days

Gross pathology:

No deviations from normal morphology were found in the animals of the 2000 mg/kg bw dose group.
Dilatation of the small intestine was observed in one male and one female of the 5000 mg/kg bw dose group. In the same female hemorrhagic lungs were detected.

Any other information on results incl. tables

Signs and symptoms:

Observations

Exposure day: hours

Day of post-exposure period

Observation

1

2

3

5

1

2

3

4

5

6

7

8

9

10

11

12

13

>13

2000 mg/kg

Dyspnea

X

X

X

X

X

X

X

X

Ruffled fur

X

XX

XX

XX

XX

X

X

X

X

Diarrhea

X

X

Body positioncurved

X

X

X

X

X

X

5000 mg/kg bw

Sedation

X

X

X

X

Dyspnea

XX

XX

XX

XX

XX

X

X

X

XX*

XX

XX

X

X

X

Ruffled fur

X

XX

XX

XX

XX

XX

XX

XX

XX#

XX

X

X

X

X

X

Diarrhea

X

X

Body position curved

X

X

X

X

X

X

X

X

X

X

X

X

X=slight XX=moderate XXX=marked

*=only in animal N°1 (male)

#=only in animal N°3 (male)

Body weight and standard deviations:

	Males
dose mg/kg	Day 1	Day 7	Day 14
2000	193/7.2	258/8.9	292/9.3
5000	205/7.0	230/21.7	293/27.2

	Females
Dose mg/kg	Day 1	Day 7	Day 14
2000	176/3.4	202/6.2	214/5.3
5000	193/5.3	/	/

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Upon an acute oral administration and a 14 day post-treatment observation period, the following LD50 (with 95% confidence limits calculated, where possible) was determined for TK 11907.
LD50 in male rats: > 2000, perhaps > 5000 mg/kg bw.
LD50 in female rats: > 2000, < 5000 mg/kg bw.
LD50 in rats of both sexes: > 2000, < 5000 mg/kg bw.
.

Executive summary:

The study, project no. 851045, was conducted to determine the acute oral toxicity of TK 11907 in albino rats.

All the work was done at the Sisseln facility (CH-4332 Stein/Switzerland).

This experiemnt was performed according to the OECD 401.

Upon the acute oral administration and a 14 day post-treatment observation period, the following LD50 was determined for TK 11907.

LD50 in male rats: > 2000, perhaps > 5000 mg/kg bw.

LD50 in female rats: > 2000, < 5000 mg/kg bw.

LD50 in rats of both sexes: > 2000, < 5000 mg/kg bw.

Symptoms

Dyspnea, ruffled fur, and curved body position were seen, being common symptoms in acute tests.

Additionally, diarrhea was observed in both dose groups on the administration and on day 1 after the administration.

Sedation was observed in the animals of the 5000 mg/kg bw dose group from 2 hours up to day 1 after the administration.

The surviving animals recovered within 6-12 days.

Mortality

At 2000 mg/kg bw: No mortality

At 5000 mg/kg bw: 2 males (40%: 1 day of post exposure period and day 6 post exposure)) and 5 females (100%. 1 day 1 and 4 day 2 of post exposure)