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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9 January 2011 to 8 March 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Test guideline and GLP compliant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 4,4-biphenol
- Physical state:powder
- Analytical purity:99.9%
- Purity test date: 9 September 2011
- Lot/batch No.: 071111370
- Expiration date of the lot/batch: 11 July 2016
- Storage condition of test material: Ambient room temperature
- Other: description off white to white cream coloured powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Italia S.p.A.
- Age at study initiation: 7-9 weeks (6-8 weeks at delivery, 176-188g on delivery)
- Weight at study initiation: 267-302g for males and 206-239g for females
- Fasting period before study: not applicable
- Housing: Individually in polycarbonate cages with stainless steel mesh lid and floor
- Diet (e.g. ad libitum): 4 RF 18 ad libitum
- Water (e.g. ad libitum): ad libitum supplied from water bottles
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-15
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 9 January 2012 To: 24 January 2012

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of body surface
- % coverage: 10
- Type of wrap if used:surgical gauze covered by synthetic film to provide a semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after exposure the test material was removed by gentle swabbing with cotton wool and lukewarm water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: yes, 0.5 ml of water added to weighed amount of test material at time of application
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations, bodyweights recorded on days -1, 1, 8 and 15
- Necropsy of survivors performed: yes, on day 15
- Other examinations performed: clinical signs, body weight, morbidity/mortality
Statistics:
Median lethal dose exceeded the limit dose level so no statistical analysis required

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Median lethal dose exceeds the limit dose level of 2000 mg/kg bw
Mortality:
No rats died
Clinical signs:
No clinical signs were observed in male or female rats.
Body weight:
Bodyweight changes during the observation period were within the expected ranges.
Gross pathology:
A single ovarian cyst in one female was considered incidental.
No other macroscopic abnormalities were observed.
Other findings:
No effects were observed at the treatment site.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dermal dose was greater than 2000 mg/kg bw. On the basis of the results, 4,4'-biphenol does not require classification according to the requirements of Council regulation EC No 1272/2008.
Executive summary:

The acute toxicity of 4,4-Biphenol was investigated following single dermal administration to the rat. 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours under a semi-occlusive dressing. Following an observation period of 14 days, all animals were killed and subjected to necropsy examination.

No mortality occurred and no signs of toxicity were observed in male or female rats during the observation period. The body weight changes during the study were within the expected range. A single ovarian cyst was recorded for one female animal but was considered to be an incidental finding. No significant abnormalities were found at necropsy in the other treated animals and no abnormalities were observed at the treated site.

4,4 -Biphenol had no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The median lethal dose was greater than 2000 mg/kg. European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and subsequent revisions) indicate no classification is required.