4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 22 March, 2002 to 5 April 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

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:

other: Limit test

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride

EC Number:

500-240-0

EC Name:

4,4'-Isopropylidenediphenol, polymer with 1-chloro-2,3-epoxypropane, propane-1,2-diol acrylate and succinic anhydride

Cas Number:

68958-77-0

Molecular formula:

UVCB, major component represented by di-functionalised BADGE (HPA-SA-BADGE-SA-HPA): C41H52O16 Other constituents present at >10%: Mono-functionalised BADGE (BADGE-SA-HPA): C35H44O14 Dimers (HPA-SA-BADGE-SA-BADGE-SA-HPA): C66H82O24

IUPAC Name:

2-Propenoic acid, monoester with 1,2-propanediol, polymer with 2-(chloromethyl)oxirane, dihydro-2,5-furandione and 4,4'-(1-methylethylidene)bis[phenol]

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

other: CD rats of Sprague-Dawley origin (Hsd:Sprague-Dawley (CD))

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals chosen for this study were selected from a stock supply of healthy male and female CD rats of Sprague-Dawley origin (Hsd:Sprague-Dawley (CD)) obtained from Harlan U.K. Ltd., Bicester, Oxon, England. They were in the weight range of 227 to 285 g and approx 8-11 wk of age prior to dosing (Day 1). All the rats were acclimatised to the experimental environment for a period of 8 d prior to the start of the study. The rats were allocated without conscious bias to cages within the treatment group. They were housed individually in metal cages (RS Biotech Sub-Dividable Rodent Cages - polished stainless steel) until Day 5 when they were returned to group housing. The cages were fitted with grid floors to ensure rapid removal of waste material to undertrays. The cages were suspended in mobile stainless steel racks in Building F21 Room 28. A standard laboratory rodent diet (Special Diet Services RMl(E) SQC expanded pellet) and drinking water were provided ad libitum. The batch (es) of diet used for the study was analyzed by the Supplier for certain nutrients, possible contaminants and micro-organisrns. Results of routine physical and chemical examination of drinking water, as conducted by the supplier, are made available to Huntingdon Life Sciences Ltd. at regular intervals throughout the year. Animal room environmental controls were set to maintain temperature within the range 22 ± 3°C and relative humidity 40 - 70%. Any minor deviations from these ranges would not have had an adverse effect on the animals and would not affect the integrity or validity of the study. These environmental parameters were recorded daily and the permanent record archived with other departmental raw data. Lighting was controlled by means of a time switch to provide 12 h of artificial light (0600 - 1800 hours GMT) in each 24 h period. Each animal was identified by tail marking. Each cage was identified by a coloured label displaying the dose level, study schedule number, animal mark and the initials of the Study Director and Home Office licensee.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

propylene glycol

Details on dermal exposure:

One day prior to treatment, hair was removed from the dorso-lumbar region of each rat with electric clippers taking care to avoid damaging the skin, exposing an area equivalent to approx 10% of the total body surface area. The test substance was applied by spreading it evenly over the prepared skin. The treatment area (approx 50 mm x 50 mm) was covered with porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal. Treatment in this manner was performed on Day 1 (day of dosing) of the study only.

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex

Control animals:

not required

Details on study design:

Dose level (volume): 2000 mg/kg bw (5 mL/kg bw)
DOSAGE PREPARATION: The test substance was formulated at a maximum practical concentration of 40% wlv in propylene glycol.
Duration of observation period following administration: 14 d
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: Yes

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 occurred.

Clinical signs:

other: No systemic response to treatment following a single dermal application. Very slight dermal irritation (Grade 1 erythema with or without Grade 1 oedema or Grade 1 oedema only) was observed in one male and two females following removal of the dressings, re

Gross pathology:

No abnormalities were revealed at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

Under the test conditions, the dermal LD50 of the substance in rats was > 2000 mg/kg bw.

Executive summary:

A study was conducted to determine the acute dermal toxicity of the test substance according to OECD Guideline 402 and EC Method B.3, in compliance with GLP. A group of 10 rats (five males and five females) received a single topical application of the test substance, formulated at a maximum practical concentration in propylene glycol, corresponding to a dose level of 2,000 mg/kg bw. All animals were killed and examined macroscopically on Day 15, the end of the observation period. There was no systemic response to treatment in any animal throughout the study. Very slight dermal irritation (Grade 1 erythema with or without Grade 1 oedema or Grade 1 oedema only) was observed in three animals following removal of the dressings, resolving completely by Day 4. No dermal irritation was noted in the remaining seven animals throughout the study. A low bodyweight gain was recorded for one male and three females on Day 8 and one female on Day 15. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were revealed at the macroscopic examination at study termination on Day 15. Under the test conditions, the acute dermal LD50 of the test substance in rats was greater than 2,000 mg/kg bw (Blanchard, 2003).