Glycerol, propoxylated, esters with acrylic acid

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:

April 25, 1983 - June 01, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

C-486 (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:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Glycerol, propoxylated, esters with acrylic acid

EC Number:

500-114-5

EC Name:

Glycerol, propoxylated, esters with acrylic acid

Cas Number:

52408-84-1

Molecular formula:

(C3H6O)m(C3H6O)n(C3H6O)oC12H14O6

IUPAC Name:

Poly[oxy(methyl-1,2-ethanediyl)], .alpha.,.alpha.',.alpha.''-1,2,3- propanetriyltris[.omega.-[(1-oxo-2-propenyl)oxy]]-

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton-Dutchland Inc., Denver, Pennsylvania
- Age at study initiation: Young adults
- Weight at study initiation: Males: 2.1-2.3 kg; Females: 2.2-2.7 kg
- Housing: Individually housed in a suspended, stainless steel cages
- Diet: Purina rabbit chow, ad libitum
- Water: ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 60- 70 °F
- Photoperiod: 12 h light/ 12 h dark

Administration / exposure

Type of coverage:

open

Vehicle:

corn oil

Details on exposure:

TEST SITE
- Area of exposure: Back of the animal, 10 % of the total body surface area
- Time intervals for shavings or clipplings: Reclipped as necessary during the study

REMOVAL OF TEST SUBSTANCE
- Site was wiped with dry gauze on the day following each dose, after dermal observations

TEST MATERIAL
- Amount(s) applied: 500 mg/kg bw/d (2.0 mL/kg/d)
- Concentration: 25 % w/v in vehicle
- Constant volume or concentration used: Yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 2 mL/kg/d (corn oil)

USE OF RESTRAINERS FOR PREVENTING INGESTION: Yes

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

14 days

Frequency of treatment:

Daily, 5 days/week for 2 weeks

Doses / concentrations

Dose / conc.:

500 mg/kg bw/day (nominal)

No. of animals per sex per dose:

five

Control animals:

yes, concurrent vehicle

Details on study design:

- Rationale for animal assignment: Randomly assigned using random number table

Positive control:

No

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

DERMAL IRRITATION: Yes
- Time schedule for examinations: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Pretest and weekly during the study

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

None

Statistics:

Variance of the two groups were tested for equality using F-test followed by t-test (if variances were equal) or Welch's test (if variances differed)

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Nasal discharge, ocular irritation, fecal or urinary staining, necrosis and bruising of the ears, necrosis on the neck, necrosis and swelling of the scrotum, respiratory rate irregularities, hypoactivity and hyperthermia of the ears.

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

Dermal effects included moderate to severe erythema and edema, necrosis, eschar formation with subsequent exfoliation, ataxia, desquamation and fissuring.

Mortality:

mortality observed, treatment-related

Description (incidence):

One female was found dead on Day 12

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

- Body weight gain in animals in treatment group was lower than control group throughout the dosing period
- Animals gained weight in recovery period

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

Description (incidence and severity):

Presence of dermal lesions like desquamation, eschar, scabs and/or sores and exfoliations

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Observations in female animal which was found dead on Day 12:
- Slight to moderate acute fibrinopurulent pericarditis, some purulent inflammation in both kidneys and a slight chronic meningitis with few scattered small granulomas in the cerebrum and extensive dermal necrosis at the application site associated with an acute inflammatory reaction

Observations in animals sacrificed after 2 weeks:
- Fairly extensive dermal necrosis accompanied by an acute purulent inflammatory response.

Observations in animals sacrificed after 4 weeks:
- Inflammation with a conspicuous increase in the amount of dense fibrocollagenous tissue; minimal to mild inflammatory process in the epicardium and/ or pericardium (in 3 females).

Histopathological findings: neoplastic:

not examined

Effect levels

Dose descriptor:

LOAEL

Effect level:

500 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

Remarks on result:

other: effects likely secondary to local irritation

Target system / organ toxicity

Critical effects observed:

no