4,4'-isopropylidenebis[2-allylphenol]

Endpoint summary

Description of key information

1)The acute oral toxicity study was performed to assess the acute oral toxicity of the test item in the rat.
2)The acute dermal toxicity study was performed to asses the acute dermal toxicty of the test item, (TK 11907), in the rat.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

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.

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.

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)

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

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.

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	/	/

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)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Date of acclimatization: 27 November 1985; Date of application: 3 December 1985 ; Date of completion: 17 December 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No GLP methodology followed.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

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

Sex:

male/female

Details on test animals or test system and environmental conditions:

-RationaIe: The rat has been selected for this test as being a Standard species for the determination of an acute dermal LD50.
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Initial Body Weight Range: 203 - 242 g
- Initial Age: 7-8 weeks
- Tndividual Identification: By cage number
- Husbandry: The animals were kept under conventional laboratory conditions. They were caged individually in Macroion cages type 2 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.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

Liquid substance, used undiluted.

Details on dermal exposure:

- Volume (ml/kg body weight) applied: 2
- Pretreatment: Approximately 24 hours before treatment an area on the back of the rat of at least 10% of the body surface was shaved with an
electric clipper.

- Application: The required amount of the test substance was evenly dispersed on the skin. It was covered with a gauze-lined semiocclusive dressing, which was fastened around the trunk with an adhesive elastic bandage.After an exposure period of 24 hours the dressing was removed and the skin was cleaned with lukewarm water. Thereafter the reaction of the skin was appraised repeatedly.

days

Duration of exposure:

One single dose, applied onto the skin of the back.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females (in total 10 rats)

Control animals:

other:

Details on study design:

- Duration of observation period following administration: 14 days
- Mortality: daily, a.m. and p.m. on working days, a.m. on weekends
- Signs and Symptoms: daily
- Body weight: on days 1, 7, and 14
- Necropsies: The animals were submitted to a gross necropsy at the end of the observation period.

Statistics:

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

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: Dyspnea, ruffled fur, and abnormal body positions were seen, being common symptoms in acute tests. Additionally, erythema reactions were observed from day 1 to day 8 after the application and edema reactions from day 4 to day 8 after the application. The

Other findings:

Autopsie: No deviations from normal morphology were found.

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

XX

XX

XX

XX

X

X

X

X

X

X

X

X

X

X

X

X

Ruffled fur

X

X

X

X

X

X

X

X

X

X

X

X

X

Body position ventral

X

X

X

X

X

Body position curved

X

X

X

X

Erythema

X

X

X

X

Edema

X

X

X

X

X

X=slight XX=moderate XXX=marked

Body weight and standard deviations:

	Males
dose mg/kg	Day 1	Day 7	Day 14
2000	211/5.5	256/8.5	305/12.1

	Females
Dose mg/kg	Day 1	Day 7	Day 14
2000	216/15.2	214/13.4	226/9.8

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Upon an acute dermal application and a 14 day post-treatment observation period, the following LD50 (with 95% confidence limits calculated where possible) was determined for TK 11907.

Executive summary:

The study, project no. 851048, was conducted to determine the acute dermal 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 405.

Upon an acute dermal application 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 mg/kg bw.

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

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

Symptoms

Dyspnea, ruffled fur, and abnormal body positions were seen, being common symptoms in acute tests.

Additionally, erythema reactions were observed from day 1 to day 8 after the application and edema reactions from day 4 to day 8 after the application.

The animals recovered within 13 days.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

1)This study was conducted to determine the acute oral toxicity of TK 11907 in albino rats.

Upon the 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

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)

2)The study was conducted to determine the acute dermal toxicity of TK 11907 in albino rats.

Upon an acute dermal application 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 mg/kg bw.

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

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

Symptoms

Dyspnea, ruffled fur, and abnormal body positions were seen, being common symptoms in acute tests.

Additionally, erythema reactions were observed from day 1 to day 8 after the application and edema reactions from day 4 to day 8 after the application.

The animals recovered within 13 days.

Justification for selection of acute toxicity – oral endpoint
Only this study is available

Justification for selection of acute toxicity – inhalation endpoint
In accordance with column 2 of REACH (Regulation (EC) No 1907/2006) Annex VIII, the acute toxicity by inhalation study (required in section 8.5.2) does not need to be conducted as acute toxicity studies are available for the oral and dermal routes of exposure. Furthermore, the substance is marketed in a form which are is not inhalable.

Justification for selection of acute toxicity – dermal endpoint
Only this study is available

Justification for classification or non-classification

Based on the above mentioned results the substance does not need to be classified according to CLP regulation (Regulation EC No.1272/2008) and DSD (Directive 67/548/EEC).