2-ethyl-2-[[(1-oxoallyl)oxy]methyl]-1,3-propanediyl diacrylate; 2,2-bis(acryloyloxymethyl)butyl acrylate; trimethylolpropane triacrylate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific standards and described in sufficient details

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Principles of method if other than guideline:

TMPTA (500 mg/kg bw) was applied to the backs of New Zealand White albino rabbits (5/sex/dose) once daily, 5 days/week for 2 weeks. Six animals per group were sacrificed after 15 days and remaining 4 animals after 30 days. Animals were monitored for the clinical signs and mortality, body weight gains, dermal reactions, gross pathology and histopathology.

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-ethyl-2-[[(1-oxoallyl)oxy]methyl]-1,3-propanediyl diacrylate

EC Number:

239-701-3

EC Name:

2-ethyl-2-[[(1-oxoallyl)oxy]methyl]-1,3-propanediyl diacrylate

Cas Number:

15625-89-5

Molecular formula:

C15H20O6

IUPAC Name:

2,2-bis(prop-2-enoyloxymethyl)butyl prop-2-enoate

Constituent 2

Reference substance name:

Trimethylolpropane Triacrylate (TMPTA)

IUPAC Name:

Trimethylolpropane Triacrylate (TMPTA)

Details on test material:

- Name of test material (as cited in study report): Trimethylolpropane Triacrylate (TMPTA)
- Physical state: Clear liquid
- Lot/batch No.: 4-78
- Storage condition of test material: Stored at room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Marland Breeding Farms, Inc. Hewitt, New Jersey
- Weight at study initiation: Male-2.5 (2.3 - 3.0) kg; Female-2.5 (2.2 - 2.9) kg
- Housing: Individually housed in suspended stainless steel cage
- Diet: Purina rabbit chow, ad libitum
- Water: Ad libitum
- Acclimation period: At least one week

ENVIRONMENTAL CONDITIONS
- Photoperiod: 12 h light/ 12 h dark

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: Back
- Time intervals for shavings or clippings: Clipping was repeated as necessary throughout the study

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg/kg bw
- Constant volume or concentration used: Yes

USE OF RESTRAINERS FOR PREVENTING INGESTION: Yes

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Not applicable

Duration of treatment / exposure:

Two weeks

Frequency of treatment:

Daily, five days/week for two weeks

Doses / concentrations

Remarks:

Doses / Concentrations:
500 mg/kg bw/day
Basis:
nominal per unit body weight

No. of animals per sex per dose:

Five

Control animals:

yes, concurrent no treatment

Details on study design:

- Rationale for animal assignment: Random

Positive control:

None

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Pretest, weekly during treatment and terminally

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

None

Statistics:

None

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Dermal irritation:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY:
- Decreased motor activity and nasal discharge during the study
- The ears of some animals came in contact with the test material and subsequently exhibited edema and scab formation

BODY WEIGHT AND WEIGHT GAIN: Four animals (2 males and 2 females) exhibited slight weight losses

DERMAL IRRITATION:
- Animals exhibited severe erythema with desquamation, necrotic skin and eschar formation
- Exfoliation (sloughing of the eschar tissue) occurred during the second week of the post-dose period
- Fissuring of the skin and slight to moderate edema and atonia were also noted in most animals during the 2 week treatment period; these signs decreased in incidence and severity during the post-dose period

HISTOPATHOLOGY:
Observation in animals sacrificed after two weeks:
- No evidence of a systemic effect
- Severe necrosis of the epithelium and upper dermis

Observation in animals sacrificed after four weeks:
- No evidence of a systemic effect
- Epithelial and subepithelial dermal necrosis persisted two weeks after termination of treatment

Effect levels

Dose descriptor:

NOAEL

Remarks:

sytemic

Effect level:

> 500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: mortality; body weight; dermal reactions; gross pathology and histopathology

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

A systemic NOAEL for trimethylolpropane triacrylate (TMPTA) was considered to be 500 mg/kg bw. A LOAEL of 500 mg/kg bw/day can be set for local effects.

Executive summary:

A repeated dermal toxicity study was performed to assess the dermal irritation caused by trimethylolpropane triacrylate (TMPTA) in New Zealand White rabbits.

 

Groups of New Zealand White rabbits (5/sex/dose) received topical application of TMPTA (500 mg/kg bw) to the back, once daily, 5 days/week for 2 weeks. Six animals per group were sacrificed after 15 days and remaining 4 animals per group after 30 days.

 

Signs of severe dermal irritation observed in rabbits treated with TMPTA. Animals exhibited severe erythema with necrotic skin and eschar formation, edema, atonia, fissuring of the skin, desquamation and exfoliation of eschar tissue. Signs of severe irritation persisted in most animals throughout the post-treatment period. Motor activity decreased and nasal discharge occurred in several animals in the treated group, few animals exhibited slight body weight losses.

 

Microscopic examination of selected tissues revealed no evidence of systemic toxicity resulting from administration of TMPTA. Evaluation of treated skin revealed severe necrosis of the epithelium and upper dermis (after 15 days) and epithelial and subepithelial dermal necrosis (after 30 days).

 

In conclusion, as no systemic substance related effects were observed the systemic NOAEL of trimethylolpropane triacrylate (TMPTA) was considered to be > 500 mg/kg bw.