Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
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:
publication
Title:
Unnamed
Year:
2003

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
subacute study according to EPA Dermal Bioassay Workshops (April 28-29, 1987 and May 18-19, 1988), 14 d dose range finder

GLP compliance:
yes
Test type:
other: 14 d dose-range finding study
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): triethylene glycol dimethacrylate

Test animals

Species:
mouse
Strain:
other: C3H/HeNHsd
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague-Dawley (Indianapolis, IN)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2-3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-77
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
open
Vehicle:
acetone
Details on dermal exposure:
TEST SITE
applied to the clipped interscapular region of the back
- Type of wrap if used: no wrap
- Time intervals for shavings or clipplings: during the week prior to the first dose and as needed during the dosing period, the fur was clipped from the dorsal area of the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL
- Concentration (if solution): 25, 50, 100%

USE OF RESTRAINERS FOR PREVENTING INGESTION: no
Duration of exposure:
14 d
Doses:
50 µl of 25, 50, 100% corresponding to approximately 500, 1000 and 2000 mg/kg bw/d

(density = 1.092 g/cm³; body weight assumed 25 g; purity 91%; resulting in 500 mg/kg bw/d for 25% dose group,1000 mg/kg bw/d for 50% dose group and 2000 mg/kg bw/d for 100% dose group)
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: dose was applied daily for 14 days
Mortality:
no mortality occurred in all dose groups
Clinical signs:
no significant clinical observations
Gross pathology:
No necropsy findings on internal organs

Applicant's summary and conclusion

Interpretation of results:
not classified
Conclusions:
The dermal LD50 of TREGDMA is greater than 2000 mg/kg bw even when this dose is not applied once, but daily for 14 days.
Executive summary:

In a dose-range-finding study for a repeated-dose dermal toxicity study, TREGDMA (95% a.i.) was applied to the shaved skin of 5 male C3H/HeNHsd mice/dose at dose levels of 0, 25, 50 and 100% (applied in 50 µL) corresponding to approx. 500, 1000 and 2000 mg/kg bw/d for 14 days.

No mortality, no significant clinical signs, and no necropsy findings on internal organs were observed in all dose groups.

Desquamation and exfoliationwas the only skin finding noted during the study and at necropsy in the 50 and 100% TREGDMA treated groups. Microscopic changes in the treated skin primarily consisted of dermatitis, intracorneal pustule formation, acanthosis, and hyperkeratosis. Epidermal necrosis or ulceration was not evident in the treated mice. 

The dermal LD50 in this study was greater than 2000 mg/kg bw even when this dose is not applied once, but daily for 14 days.