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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981-03-03 to 1981-03-17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented study report which meets basic scientific principles (Klimish et al., 1997). The study was performed prior to the adoption of the OECD Guidelines. Purity of test material was not noted.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Eight test animals were used in the present study (4/sex). Environmental conditions are reported not completely.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): CR-39® Monomer
- Substance type: organic
- Physical state: liquid
- Analytical purity: data not available
- Impurities (identity and concentrations): data not available
- Composition of test material, percentage of components: data not available
- Isomers composition: data not available
- Purity test date: data not available
- Lot/batch No.: 479-768
- Expiration date of the lot/batch: data not available
- Radiochemical purity (if radiolabelling): not applicable
- Specific activity (if radiolabelling): not applicable
- Locations of the label (if radiolabelling): not applicable
- Expiration date of radiochemical substance (if radiolabelling): not applicable
- Stability under test conditions: Test material stability statement was provided by the sponsor.
- Storage condition of test material: at room temperature in a locked test compound cabinet.

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Langshaw Farms, Augusta, Michigan
- Age at study initiation: young adult animals
- Weight at study initiation: ranged from 2.25 to 2.50 kilograms.
- Fasting period before study: no
- Housing:individually housed in steel wire-bottomed cages suspended above the droppings.
- Diet (e.g. ad libitum): Purina Certified Rabbit Chow, 5322 ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: The rabbits were quarantined and acclimated to laboratory conditions for 13 days prior to initiation of the study


ENVIRONMENTAL CONDITIONS
data not available

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Approximately 24 hours prior to the dermal application the backs of the rabbits were clipped free of hair. The twenty-four hour waiting period allowed recovery of the stratum corneum from the disturbance that accompanies the close clipping procedure and also permitted healing of any microscopic abrasions possibly produced during this process.

TEST SITE (approximately 240 cm^2).
- Area of exposure: back
- % coverage: 10
Each test site was immediately occluded with a layer of 4-ply gauze, two single layers thick.
- Type of wrap if used: rubber latex dental dam and the dental dam taped at the edges with 1 inch Micropore tape to form an airtight occlusive wrap.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was wiped off.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): not reported (see Doses)
- Concentration (if solution): no
- Constant volume or concentration used: no; individual dose amounts were calculated using day 0 body weights.


VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable
- Concentration (if solution): not applicable
- Lot/batch no. (if required): not applicable
- Purity: not applicable
Duration of exposure:
24 hours
Doses:
undiluted 10 mL/kg bw
No. of animals per sex per dose:
4males /4 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at frequent intervals during the day of dosing and at least twice daily thereafter for a total of 14 days. All surviving animals selected for the study were weighed one day prior to dosing, on day of dosing, 6 and 13 days after dosing.
- Necropsy of survivors performed: yes (as well as of animals foud dead) on the visceral and thoracic cavities
- Other examinations performed: clinical signs, body weight,organ weights, gross signs of systemic toxicity and mortality. Room conditions as well as availability of adequate food and water were checked and any noteworthy conditions recorded.
Statistics:
The WIL computer program based on the techniques of Litchfield and Wilcoxon were used to calculate the LD50 if mortality occurred at an adequate number of dose levels [Litchfield, J. J. and F. Wilcoxon, "A Simplified Method of Evaluation of Dose-Effect Experiments," J. Pharm. and Exp. Ther., 99-113 (1949)].

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 10 mL/kg bw
Remarks on result:
other: mortality in 3/8 animals
Mortality:
Three females were found dead on day 2 of the study.
Clinical signs:
Surviving animals appeared slightly emaciated with anorexia, adipsia, decreased defecation and tufts of hair on the cage paper. Evaluation of local skin reactions revealed moderate to slight erythema and edema during days 1-3.
Body weight:
Mean body weight changes appeared to be slightly decreased at the six day interval (see table 1 in "Remarks on results including tables and figures")
Gross pathology:
Examination of the visceral and thoracic cavities of the test animals at necropsy by the pathologist revealed:
Intraperitoneal fluid red, spleen mottled light (240F).
Exterior surface of stomach reddened and interior hemorrhagic, vaginal area congested (red black in color and passage not distinguishable for examination (244F). Irregular, pale, yellow foci noted over the liver (243F and 229M). No significant gross pathologic findings (all others).
Other findings:
no

Any other information on results incl. tables

Table 1: Means and statistics of individual body weights (kg)

 

Males

Females

Statistic

Value

Statistic

Value

Day -1

Mean

S.D.

S.E.

N

2.400

0.082

0.0041

4

Mean

S.D.

S.E.

N

2.400

0.108

0.054

4

Day 0

Mean

S.D.

S.E.

N

2.425

0.104

0.052

4

Mean

S.D.

S.E.

N

2.375

0.150

0.075

4

Day6

Mean

S.D.

S.E.

N

2.067

0.247

0.142

3

Mean

S.D.

S.E.

N

2.200

0.424

0.300

2

Day13

Mean

S.D.

S.E.

N

2.417

0.208

0.120

3

Mean

S.D.

S.E.

N

2.525

0.177

0.125

2

Applicant's summary and conclusion

Interpretation of results:
sligthly toxic
Remarks:
Migrated information Criteria used for interpretation of results: other: High Production Volume Chemicals Branch Risk Assessment Division Office of Pollution Prevention and Toxics Environmental Protection Agency US
Conclusions:
As only one dose level was dosed and produced mortality in 3/8 of the test animals, an LD50 could not be calculated. From the data presented the LD50 is greater than 10 mL/kg of body weight.
Executive summary:

When CR-39 was administered dermally at one dose level of 10 mL/kg bw to the nonabraded skin of 8 New Zealand White rabbits (4 males and 4 females), signs of systemic toxicity occurred (anorexia, adipsia, emaciation and decreased defecation) during the post dose observation period of 14 days. Three/eight animals were found dead on day 2 of the study. Positive gross pathologic findings were observed in four/eight of the test animals. From the data presented in the report the LD50 of CR-39 is greater than 10 mL/kg bw (11,430 mg/kg bw).