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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 26 February, 2002 to 21 March, 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

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:

Animals chosen for this study were selected from a stock supply of healthy male and female CD rat of Sprague-Dawley origin (Hsd:Sprague-Dawley(CD)) obtained from Harlan U.K. Ltd., Bicester, Oxon, England. They were in the weight range of 100 to 141 g and approx 5-7 wk of age prior to dosing (Day 1). All the rats were acclimatised to the experimental environment for a minimum period of 5 d prior to the start of the study. Rats were allocated without conscious bias to cages within the treatment groups. They were housed in groups of 3 rats of the same sex in metal cages with wire mesh floors in Building F21 Room 28. A standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet) and drinking water were provided ad libitum. Access to food only was prevented overnight prior to and approx 4 h after dosing. Each batch of diet used for the study was analyzed for certain nutrients, possible contaminants and micro-organisms. 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 GMT) in each 24 h period. Each animal was identified by tail marking.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

The test substance was formulated at a concentration of either 20 or 200 mg/mL in DMSO and administered at a volume of 10 mL/kg bw. The test substance was prepared on the day of dosing. The absorption of the test substance was not determined. Chemical analysis of the homogeneity, stability and purity of the test substance was not undertaken as part of this study and remains the responsibility of the Sponsor.

Doses:

200 mg/kg bw, 2000 mg/kg bw

No. of animals per sex per dose:

3/sex/dose

Control animals:

no

Details on study design:

A group of six fasted rats (three males and three females) received a single oral gavage dose of the test substance, formulated in dimethylsulphoxide (DMSO), at a dose level of 200 mg/kg bw using a glass syringe and plastic catheter. As results at this dosage indicated the acute lethal oral dose of the test substance to be greater than 200 mg/kg bw, in compliance with the guidelines, a further group of six fasted rats (three males and three females) was similarly dosed at 2000 mg/kg bw to complete the study. The day of dosing was designated Day 1. Cages of rats were checked at least twice daily for any mortalities. Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 d after dosing. The bw of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bw were calculated. All animals were killed on Day 15 by carbon dioxide asphyxiation. All animals were subjected to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

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:

There were no deaths following a single oral gavage dose of the test substance to a group of six rats (three males and three females) at a dose level of either 200 or 2000 mg/kg bw.

Clinical signs:

other: Clinical signs of reaction to treatment comprised of abnormal gait and piloerection, seen in all animals at both dosages. In addition, increased salivation (two males and all females at 200 mg/kg bw and all females at 2000 mg/kg bw), hunched posture (all

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 conditions of the study, the acute oral lethal dose to rats of the substance was found to be greater than 2000 mg/kg bw.

Executive summary:

A study was performed to assess the acute oral toxicity of the test substance to the rat according to the OECD Guideline 423 and EU Method B.1 tris, in compliance with GLP. A group of six fasted rats (three males and three females) received a single oral gavage dose of the test substance, formulated in dimethylsulphoxide (DMSO), at a dose level of 200 mg/kg bw. As results at this dosage indicated the acute lethal oral dose of the test substance to be greater than 200 mg/kg bw, a further group of six fasted rats (three males and three females) was similarly dosed at 2,000 mg/kg bw. All animals were killed as scheduled and examined macroscopically on Day 15, the end of the observation period. Clinical signs of reaction to treatment comprised of abnormal gait and piloerection, seen in all animals at both dosages with increased salivation and hunched posture observed in rats at both dosages and pallor of the skin in animals at 2000 mg/kg only. Recovery of rats, as judged by external appearance and behaviour, was complete by Day 2. 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 conditions of the study, the acute oral LD50 of the test substance in rats was greater than 2,000 mg/kg bw (Blanchard, 2002).