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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 April 2013 -- 10 July 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
4,4'-lsopropylidenediphenol, ethoxylated, esters with acrylic acid and isononanoic acid
EC Number:
923-007-9
IUPAC Name:
4,4'-lsopropylidenediphenol, ethoxylated, esters with acrylic acid and isononanoic acid
Constituent 2
Reference substance name:
Esterification products of 4,4'-Isopropylidenediphenol, ethoxylated and prop-2-enoic acid and 3,5,5-trimethylhexanoic acid
EC Number:
919-846-5
Cas Number:
1187203-83-3
Molecular formula:
Not available for this UVCB.
IUPAC Name:
Esterification products of 4,4'-Isopropylidenediphenol, ethoxylated and prop-2-enoic acid and 3,5,5-trimethylhexanoic acid
Test material form:
other: colorless viscous liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: the males had a mean body weight of 359 g (range: 345 g to 375 g) and the females had a mean body weight of 205 g (range: 199 g to 210 g).
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 11 June 2013 to 28 June 2013

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure
- Washing: yes in females only

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume: no
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
Ten rats (five males and five nulliparous and non pregnant females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight on the day of group allocation, just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).
Statistics:
no

Results and discussion

Preliminary study:
no
Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No unscheduled deaths occurred during the study.

Clinical signs:
other: No clinical signs indicative of systemic toxicity were observed in any animals. Four females presented with a very slight or a well-defined erythema from day 2 to day 6. Two animals from the four females had also a very slight to slight dryness of the ski
Gross pathology:
There were no macroscopic findings at necropsy.
Other findings:
no

Any other information on results incl. tables

Table 1

Sex

Female

Male

Group

historical control data

1

historical control data

2

Dose-level (mg/kg)

0

2000

0

2000

Body weight (mean (± SD))

 

 

 

 

. Day 1

236 (± 8.9)

205 (± 4.0)

362 (± 12.0)

359 (± 12.0)

. Day 8

253 (± 12.0)

229 (± 6.0)

394 (± 15.3)

384 (± 16.4)

. Day 15

273 (± 16.3)

248 (± 7.5)

441 (± 21.5)

420 (± 21.3)

Body weight change (mean (± SD))

 

 

 

 

. Days 1-8

+17 (± 11.0)

+24 (± 6.6)

+32 (± 9.1)

+25 (± 8.0)

. Days 8-15

+20 (± 7.1)

+19 (± 1.9)

+47 (± 7.5)

+36 (± 5.6)

. Days 1-15

+37 (± 16.3)

+43 (± 8.2)

+79 (± 15.6)

+61 (± 13.0)

SD: standard deviations.

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the dermal LD50 of the test item was higher than 2000 mg/kg in rats.
Therefore, the test item should not be classified as acutely toxic by dermal route according to the criteria of CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential acute toxicity of the test item following a single dermal application to rats.

This study was conducted in compliance with OECD Guideline No. 402 and the principles of Good Laboratory Practices.

 

Methods

The test item was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. From day 2, any local reactions at the treatment site were also noted. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted to a macroscopic post-mortem examination. No tissues were preserved.

 

Results

No unscheduled deaths occurred during the study.

No clinical signs indicative of systemic toxicity were observed in any animals.

Four females presented with a very slight or a well-defined erythema from day 2 to day 6. Two animals from the four females had also a very slight to slight dryness of the skin and for one of them scabs almost during the same interval.

Although two females had similar findings before application of the test item (due to clipping), all these findings were considered to be due to the test item.

No cutaneous reactions were noted in any males.

In absence of marked body weight effect, an opposite tendency was noted in body weight gain (higher in females and lower in males in comparison with historical control data). This was considered not to be test item-related.

There were no macroscopic findings at necropsy.

 

Conclusion

Under the experimental conditions of this study, the dermal LD50of the test item was higher than 2000 mg/kg in rats.

 

Therefore, the test item should not be classified as acutely toxic by dermal route according to the criteria of CLP Regulation.