4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, esters with acrylic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 June 2014 -- 04 July 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

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

Test material information

Constituent 1

Reference substance name:

4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, esters with acrylic acid

EC Number:

500-130-2

EC Name:

4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, esters with acrylic acid

Cas Number:

55818-57-0

Molecular formula:

Not applicable (UVCB substance)

IUPAC Name:

Reaction product of (4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane) and 2-propenoic acid

Test material form:

liquid: viscous

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: within ± 20% of the mean body weight of all the study animals of the same sex (245 g for females and 412 g for males).
- Fasting period before study: No
- Housing: polycarbonate cages with stainless steel lids
- 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: 17 June 2014 to 04 July 2014

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: at 24h post-exposure, with a moistened cotton pad with acetone and then water for injection

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume: no
- For solids, paste formed: yes

Duration of exposure:

24 hr

Doses:

2000 mg/kg

No. of animals per sex per dose:

ten rats (five males + 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: just before treatment, on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Statistics:

no

Results and discussion

Effect levels

Key result

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 mortality was observed in any animals.

Clinical signs:

other: No clinical signs indicative of systemic toxicity were observed in any animals. No cutaneous reactions were observed in any males. A very slight to well defined erythema at the application site was noted in all females from Day 2, 3 or 4 until Day 14 at t

Gross pathology:

There were no test item-related gross findings.
The irregular color noted in the lungs from 3/5 males treated at 2000 mg/kg/day was considered to be most probably unrelated with test item administration since this was not seen in females, and since this finding is occasionally seen in untreated rats of these strain, age, and supplier.

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	217 (± 10.3)	215 (± 7.6)	333 (± 10.3)	412 (± 15.8)
. Day 8	242 (± 10.6)	229 (± 7.1)	372 (± 9.5)	450 (± 16.5)
. Day 15	269 (± 13.0)	245 (± 6.2)	422 (± 12.6)	485 (± 25.5)
Body weight change (mean (± SD))
. Days 1-8	+25 (± 10.0)	14 (± 2.2)	+39 (± 11.5)	37 (± 4.8)
. Days 8-15	+27 (± 11.1)	17 (± 8.9)	+50 (± 12.0)	35 (± 10.5)
. Days 1-15	+52 (± 12.9)	31 (± 8.5)	+89 (± 12.8)	72 (± 12.3)

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.

Executive summary:

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

This study was based on the international guidelines (OECD No. 402 and Council Regulation No. 440/2008 of 30 May 2008, Part B.3) and was performed in compliance with the principles of Good Laboratory Practice.

 

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 for a macroscopic post-mortem examination. Macroscopic lesions were preserved in buffered formalin then destroyed at the finalization of the study report as no microscopic examination was performed.

 

Results

No unscheduled deaths occurred during the study.

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

No cutaneous reactions were observed in any males.

A very slight to well-defined erythema at the application site was noted in all females from Day 2, 3 or 4 until Day 14 at the latest along with dryness of the skin in 4/5 females from Day 4 until Day 14 at the latest. Scabs were noted in 3/5 females from Day 3 to Day 11 and wound in 1/5 females from Day 4 to Day 7.

When compared to historical control data, lower body weight gain was noted in 3/5 females between Day 1 and Day 8; and in 1/5 other females between Day 8 and Day 15. Over the period from Day 1 to Day 15, 4/5 females had a lower body weight gain when compared to historical control data.

A lower body weight gain was also noted in 3/5 males between Day 8 and Day 15 and over the study period when compared to historical control data. However, the body weight of test-item treated males on Day 1 was significantly higher than the body weight of males in historical control data. This could explain that the body weight gain of test item-treated males was lowered in some animals.

The body weights of the other animals were unaffected by the test item treatment.

There were no test item-related gross findings.

Conclusion

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 toxic by dermal route according to the criteria of CLP Regulation.