Biphenyl-2-ol, ethoxylated, esters with acrylic acid

Endpoint summary

Description of key information

 Acute toxicity, oral: 

An OECD 423 test in rats resulted in LD50 > 2000 mg/kg using Biphenyl-2-ol, ethoxylated, esters with acrylic acid as test material.

The available studies on acute toxicity of 2-phenoxyethyl acrylate show that this substance as well has low acute toxicity with LD50 in rats > 5000 mg/kg.

Thus, the similar findings support the read-across used for the toxicological evaluation of Biphenyl-2-ol, ethoxylated, esters with acrylic acid.

Acute toxicity, inhalation:

No data is available on either Biphenyl-2-ol, ethoxylated, esters with acrylic acid or 2-phenoxyethyl acrylate

Acute toxicity, dermal: 

No data is available on o-phenylphenolethyl acrylate.

The available studies on acute toxicity of 2-phenoxyethyl acrylate show that the substance has low acute toxicity with LD50 in rats > 2000 mg/kg bw . This value may be considered relevant foro-phenylphenolethyl acrylateas well.

Acute toxicity, dermal: 

No data is available on Biphenyl-2-ol, ethoxylated, esters with acrylic acid.

The available studies on acute toxicity of 2-phenoxyethyl acrylate show that the substance has low acute toxicity with LD50 in rats > 2000 mg/kg bw . This value may be considered relevant for Biphenyl-2-ol, ethoxylated, esters with acrylic acid as well.

See read-across justification attached in section 13.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

two doses were used

Qualifier:

according to guideline

Guideline:

other: National Institute of Environmental Research Notification No. 2006-29 'Regulations Regarding the Designation of Chemical Hazard Testing Institutes', Annex 5 Test Guidelines for Chemicals (December 19, 2006).

Principles of method if other than guideline:

acut toxicity study with one oral exposure, two doses 300 and 2000 mg/kg.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Ethoxylated-o-phenyl phenol acrylate, Cas no. 72009-86-0, Lot no. 71016M95
- Expiration date of the lot/batch:
- Purity test date: November 08, 2007
- Purity: 97,4 %
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: NA
- Solubility and stability of the test substance in the solvent/vehicle: NA
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: NA


FORM AS APPLIED IN THE TEST (if different from that of starting material) NA

OTHER SPECIFICS: guideline.

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Specific Pathogen Free (SPF) Rats [Crl:CD(SD)]

- Females (if applicable) nulliparous and non-pregnant: Not specified
- Age at study initiation: 9 weeks old
- Weight at study initiation: 166.9 – 196.1 g
- Fasting period before study: Overnight
- Housing: 3 animals per cage
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 oC
- Humidity (%): 50 +/- 10 %
- Air changes (per hr): 10-20 per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: January 3rd – February 1st

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Corn oil, Sigma-Aldrich Co.
- Amount of vehicle (if gavage):10mL/kg, including test item.
- Justification for choice of vehicle: Oral administration is the potential clinical route for humans, Vehicle is non-toxic at the level used in this study
- Lot/batch no. (if required): 065K0077
- Purity: NA

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Since there were no toxicity, information on animals, 300 mg/kg was selected according to the Class method test

Doses:

- 300 mg/kg (step 1)
- 300 mg/kg (step 2)
- 2000 mg/kg (step 3)
- 2000 mg/kg (step 4)

No. of animals per sex per dose:

3 animals per dose per step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days:
Clinical signs and mortality were observed at 0.5, 1, 2, 3, and 4 hours hours after administration on the dosing date (Day 1) and once each day on the following day (Day 2) to Day 15.

- Frequency of observations and weighing right before initiation of administration (Day 1 1) and Days 2, 4, 8, and 15.

- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: All organs were examined for abnormalities.

Statistics:

Not specified

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 - <= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed

Clinical signs:

other: In 3rd step at dose level of 2000 mg/kg, lateral position, subdued behavior, irregular respiration and lacrimation were observed in 3, 3, 2, and 3 animals respectively on dosing date. In 4th step at equal dose level of 2000 mg/kg,

Gross pathology:

No test item related pathological effects.

Other findings:

No other effect observed.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The acute toxicity of Ethoxylated-o-phenylphenol acrylate was tested in a single dose acute toxicity test, comparable to OECD Guideline 423. No test item related mortality was observed at the highest tested dose level 2000 mg/kg.

Executive summary:

The acute toxicity of Ethoxylated-o-phenylphenol acrylate was tested in a single dose acute toxicity test, comparable to OECD Guideline 423. The acute toxicity class method were used in female SD rats with dose level 300 and 2000 mg/kg. The test item was giving orally with corn oil as vehicle in a total volume of 10 ml/kg bw, which is acceptable according to the OECD guideline. Several clinical signs were observed, such as prone position, lateral position, subdued behavior, irregular respiration, and lacrimation. However, the symptoms were transient and only present at the day of treatment.

No mortality was observed at any of the doses, therefore the acute oral LD50 is above 2000mg/kg.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

two doses were used

Principles of method if other than guideline:

acut toxicity study with one oral exposure, two doses 2150 and 5000 mg/kg.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

5 males and 5 females per concentration, approximately 12 weeks at start. At least one week acclimatization.
Food; SSNIFF R; FA.SSNIFF, Versuchstierdiaeten; 4470 Soest

Route of administration:

oral: gavage

Vehicle:

olive oil

No. of animals per sex per dose:

5

Control animals:

no

Sex:

female

Dose descriptor:

LD50

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed

Clinical signs:

other: At highest dose, 5000 mg/kg bw; Dyspnea, staggering and overall bad condition were observed after one hour and untill 2 days. Shaggy fur was observed between 1 and 13 days. Apathy, anormalous behavior, signs of pain, spastic walking, redness of skin, dry

Interpretation of results:

sligthly toxic

Remarks:

Migrated information

Conclusions:

No mortality were observed in any of the two doses tested. The acute LD50 value is therefore above 5000 mg/kg

Executive summary:

The acute toxicity of phenoxyethyl acrylate was tested in a single dose acute toxicity test, comparable to OECD Guideline 401. Two doses were tested 2150 and 5000 mg/kg. The substance was giving orally dissolved in olive oil, total volume was 5 and 10 ml/kg bw, which is acceptable according to the OECD guideline. Several clinical signs were observed, such as dyspnoea, shaggering, shaggy fur, redness of skin and hemi paralysis. The symptoms gradually ceased within hours to two days, except shaggy fur in the highest dose. No mortality was observed at any of the doses, therefore the acute LD50 value is above 5000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to the relevant guideline under GLP conditions, inclusive certificate

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female rats obtained from Harlan Olac Ltd, Bicester Oxon, England.
Rats were housed individually in metal cages with wiremesh floor. Standard rodent diet and water were provided ad libitum.
Temperature was 21C, relative humidity was 50-51%, and 12:12 light:dark period.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Five males and five females were treated. The day before treatment, the hair was removed from the dorso-lumbar region, approximately 10% of bodysurface (5*5 cm). The test substance was applied, by spreading it evenly, and then covered by gauze, and kept in place with a non-irritative dressing, encircled firmly around the trunk.

Duration of exposure:

14 days

Doses:

2.0 g/kg

No. of animals per sex per dose:

5

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the experiment

Clinical signs:

other: No signs of systemic reactions to treatment

Gross pathology:

No macroscopic abnormalities onserved at day 15

Other findings:

Slight or well-defined erythema was observed at the site of application, for two male and three female rats on day 2. No other dermal changes and irritation has resolved at day 3.

Interpretation of results:

relatively harmless

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance can not be considered acutely toxic via the dermal route.

Executive summary:

Rats of both sexes were given 2 g/kg as a single dermal exposure and followed 14 days after exposure.

No mortality was observed . I addition no clinical signs nor macroscopic abnormalities were observed. A slight or well defined erythema was observed at the site of application for 2 and 3 male and females rats on day 2, respectively. No other dermal changes was observed, and irritation had resolved at day 3.

The substance can not be considered acutely toxic via the dermal route.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The hypothesis for a read-across approach from data on 2-phenoxyethyl acrylate to o-phenylphenolethyl acrylate is the similarity of the chemical structures and physical chemical properties of the two substances.
See attached read-across justification in section 13

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Executive summary:

No data is available for Biphenyl-2-ol, ethoxylated, esters with acrylic acid (M1142) (T).

The acute dermal toxicity of 2-phenoxyethyl acrylate was tested in female and male rats with 2 g/kg as a single dermal exposure and followed 14 days after exposure. The test was performed in accordance with EU Method B.3. No mortality, clinical signs or abnormalities were observed. A slight or well defined erythema was observed at the site of application for 2 and 3 male and females rats on day 2, respectively. No other dermal changes was observed, and irritation had resolved at day 3 (72hours). Thus, the substance can not be considered acutely toxic via the dermal route. Due to structural and pysico-chemical similarity to Biphenyl-2-ol, ethoxylated, esters with acrylic acid, low potential for acute dermal toxicity can be concluded for biphenyl-2-ol, ethoxylated, esters with acrylic acid as well.

See justification for read-across attached in section 13.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Justification for classification or non-classification

The available data on acute toxicity indicate that Biphenyl-2-ol, ethoxylated, esters with acrylic acid should not be CLP classified for acute toxicity in relation to oral, dermal or inhalational exposure.