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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Isobutyl Alcohol is both reagents used in the manufacture, as well as decomposition products of Sodium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of sodium isobutyl xanthate. In addition, xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc. Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: compact
Details on test material:
Isobutyl Alcohol is both reagents used in the manufacture, as well as decomposition products of Sodium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of sodium isobutyl xanthate.
- Name of test material (as cited in study report):Isobutanol
A sample of isobutanol, Lot No. TS3370114, CAS No. 78-83-1, was used. The test substance was a colorless, transparent, low viscosity liquid.
Gas chromatography-mass spectrometry (GC/MS) and nuclear magnetic resonance spectroscopy (NMR) techniques were independently used to confirm the sample's identity. Sample purity, measured by capillary GC, is ~ 99.9%

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Male and female New Zealand White rabbits were received from Hazleton Research Products, Inc. (Denver, PA). The strain and species were selected because of their availability and existing historical data. Rabbits were ordered to be between 2.0 and 2.3 kg (designated by the supplier to be approximately 12 to 14 weeks of age). The females were nulliparous and nonpregnant.

Periodically, a Clinical Veterinarian examined rabbits for any signs of health deficiencies. Within 1 or 2 days of receipt, all animals were assigned a unique number which was marked on the animal cage card. The rabbit number was also marked in indelible ink on 1 ear at the time of dosing.

The rabbits were housed individually in cages with wire floors (approximately 61.0 x 46.0 x 36.0 cm.). DACBQ (Deotized Animal Cage Board; Shepherd Specialty Papers, Inc.) was placed under each cage and changed regularly. An automatic timer was set to provide fluorescent lighting for a 12-hour photoperiod (approximately 0500 to 1700 hours for the light phase). Temperature and relative humidity were recorded (Cole-Parmer Hygrothermograph Seven-Day Continuous Recorder, Model No. 8368-00, Cole-Parmer Instrument Co., Chicago, IL). Temperature was routinely maintained at 61-70°F during the test period; relative humidity was routinely maintained at 40-70%. Any minor exceptions to these specified ranges were noted in the raw data.
Tap water (Municipal Authority of Westmoreland County, Greensburg, PA) was available ad libitum (except during dosing) and was delivered by an automatic watering system with demand control valves mounted on each rack. Water analyses were provided by the supplier, Halliburton NUS Environmental Laboratories, Materials Engineering & Testing Company, and Lancaster Laboratories, Inc. at regular intervals. EPA standards for maximum levels of contaminants were not exceeded. As available, water analysis reports were reviewed by the Study Director. AGWAYe PROLABe Animal Diet High Fiber Rabbit (Agway Inc.) was available ad libitum except during the actual dosing period. No analyses of chemical composition and possible contaminants of the feed were conducted by the supplier.

Animal Acclimation
The animals were acclimated for at least 5 days before dosing. Detailed clinical observations were conducted twice, at the time of receipt and during animal identification and/or dosing. In addition, rabbits were examined and weighed twice prior to dosing. Cage-side observations and mortality checks were conducted at least once daily. Animals considered unacceptable for the study, based on the clinical signs or body weights (rabbits), were rejected for use on this study.
Study Organization
The animals were weighed and inspected for health on the day of the test. Only those exhibiting a healthy state were used. Healthy animals appeared alert, active and well groomed, with no evidence of discharge, diarrhea, breathing difficulties or locomotor abnormalities. A BRRC veterinarian was available for consultation regarding any animal health concerns. Animals were randomly assigned to cages and were designated for dosing according to need and availability.

Test system

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
Readings were made at 1, 24, 48 and 72 hours and at 7 and 14 days, after the end of the contact period.
Number of animals:
3 males and 3 females
Details on study design:
The fur was removed from the dorsal area of the trunk of each rabbit using veterinary clippers a few days before dosing and the dose area was trimmed carefully (avoiding skin abrasion), as necessary, up to the day before application of the test substance. A 1-inch square gauze patch was placed over 1 intact (nonabraded) site/rabbit and secured by adhesive tape. A volume of 0.5 ml was then applied under the patch. Polyethylene sheeting was placed loosely around the trunk and secured. The animal was placed in a restraining device for the 4-hour contact period after which the coverings and as much excess test substance as possible were removed.

The test substance was applied to each of 6 rabbits (3 males, 3 females). Readings were made at 1, 24, 48 and 72 hours and at 7 and 14 days, after the end of the contact period according to the method of Draize, 1959. All rabbits were sacrificed at 14 days (ear vein injection using Euthanasia-6 Solution).

Reference
Draize, J. H. (1959). The Appraisal of Chemicals in Foods, Drugs and Cosmetics. Tbe Association of Food and Drug Officials of the United States.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.2
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Maximum score observed. One animal had a score of 1 on day 14.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Maximum score observed. One animal had a score of 1 on day 14.
Irritant / corrosive response data:
Application of 0.5 ml of isobutanol to covered rabbit skin for a 4-hour contact period produced minor to moderate erythema and edema on 6 of 6 rabbits within 1 day. (Maximum score noted on any animal for erythema or edema was 2). One rabbit had a light brown discoloration on the dose site at 1 hour. Superficial necrosis developed on this animal by 1 day; another rabbit had superficial necrosis at 7 days. Ecchymoses were apparent on 1 animal within 1 day. At 7 days, fissuring was observed on 1 animal. Four rabbits had desquamation at this time. By 14 days, alopecia was observed on 2 rabbits. Erythema and edema subsided on 5 of 6 rabbits within 14 days; minor erythema and edema persisted on 1 rabbit. Two rabbits had a normal appearance at this time.
Other effects:
No additional information available.

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Minor to moderate erythema and edema on 6 of 6 rabbits, superficial necrosis on 2, ecchymoses on 1, fissuring on 1, desquamation on 4 and alopecia on 2 from 0.5 ml. Two rabbits had a normal appearance within 14 days; minor irritation persisted on the remaining 4 rabbits.
Executive summary:

Isobutyl Alcohol is both reagents used in the manufacture, as well as decomposition products of Sodium isobutyl xanthate. Therefore, the health effects of Isobutyl Alcohol need to be considered in the assessment of sodium isobutyl xanthate.

In addition,xanthates decompose on aging to form a number of byproducts, depending on the pH, temperature, etc.Risks associated with xanthate are, therefore, a function of the breakdown of the product or un-reacted raw materials remaining in the product.

The acute dermal irritation of isobutanol was examined in a 4 -hour exposure. Minor to moderate erythema and edema on 6 of 6 rabbits, superficial necrosis on 2, ecchymoses on 1, fissuring on 1, desquamation on 4 and alopecia on 2 from 0.5 ml. Two rabbits had a normal appearance within 14 days; minor irritation persisted on the remaining 4 rabbits.