4,4'-Isopropylidenediphenol, ethoxylated

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

FROM 31 OCT 2011 to 31 MAY 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24, 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August, 1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-Isopropylidenediphenol, ethoxylated

EC Number:

500-082-2

EC Name:

4,4'-Isopropylidenediphenol, ethoxylated

Cas Number:

32492-61-8

Molecular formula:

C15H16O2.(C2H5O)n.(C2H5O)m sum of n+m: >1 - <4.5 moles EO

IUPAC Name:

2-[4-[2-[4-(2-hydroxyethoxy)phenyl]propan-2-yl]phenoxy]ethanol

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test species/strain/quality: Rat/Wistar/Crl:WI (Han) SPF
Reasons for selection: Rats were selected since this rodent species is recommended in the respective test guidelines. Wistar rats were selected since there is extensive experience available in the laboratory with this strain of rats.
Age on day 0: Young adult animals. (Male animals approx. 8 weeks, females approx. 12 weeks)
Sex: Males and females
Supplier: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
Arrival in the testing facility: Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.
Identification: Individual identification by cage cards and tail marking.
Body weight on day 0: Animals of comparable weight.

Room temperature / relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 22°C ± 3°C for temperature and of 30 – 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
Day/night rhythm: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of cage: Makrolon cage, type III
Number of animals per cage: Single housing
Feeding: VFR1(P); SDS Special Diets Services, 67122 Altrip, Germany
Drinking water: Tap water ad libitum

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The undiluted test item was applied to clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by a semi-occlusive dressing.

TEST SITE
- Area of exposure: About 40 cm2
- % coverage: at least 10% of the body surface

REMOVAL OF TEST SUBSTANCE
Route of application: Single application to the clipped epidermis (dorsal and dorsolateral parts of the trunk); covering of the application site with a semi- occlusive dressing* for 24 hours. Afterwards removal of the semi- occlusive dressing, rinsing of the application site with warm water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.73 mL/kg bw (for more details see 'Any other information on materials and methods incl. tables' section below)

Duration of exposure:

24 hours.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Examinations and frequency:
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
Clinical observations: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
Mortality: A check for any dead or moribund animals was made at least once each workday, these records are archived by Bioassay.
Pathology: Necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: No systemic clinical signs or local effects were observed during clinical examination.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Other findings:

No local effects observed

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw. According to EU CLP Regulation 1272/2008 criteria, the test substance is not classified for acute dermal toxicity.

Executive summary:

In the acute dermal toxicity study (according to OECD TG 402, Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item (purity: 99.2%) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred during the study and no signs of systemic toxicity or skin effects were observed in the animal. The mean body weight of the male animals increased throughout the study period within the normal range, the mean body weights of the female animals stagnated during the first post-exposure observation week probably due to the bandage procedure but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. The acute dermal median lethal dose (LD₅₀) was determined to be > 2000 mg/kg bw. Therefore, according to EU CLP Regulation 1272/2008 criteria, the test substance is not considered to be classified for acute dermal toxicity.