Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: dermal, other
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
EPA Test Guideline: 81-6

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: EPA Test Guideline: 81-6
Deviations:
not specified
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
Sponsor's identification
Description
Batch number
Date received
Storage conditions
PCMX
cream coloured, crystalline solid
285/13847
27 September 2001
room temperature, in the dark
Specific details on test material used for the study:
Test Material : Ottasept Technical (chloro-3,5-xylenol)
Lot Number: 9112164
Description: White crystalline powder
Date of Receipt: October 18, 1990
Expiration Date: None
Received from: Ferro Corporation
Storage: Room Temperature
Sampling : An archival sample of approximately 6 grams test material is stored in the Archives of Biodynamics, Inc.

Test animals

Species:
guinea pig
Strain:
Hartley
Details on species / strain selection:
Hartley Albino
Standard laboratory animal for dermal sensitization studies. The Hartley Albino breed was used because of its availability and because of the existing historical data base for comparative evaluation,
1 . Range-Finding:
6 (3 males, 3 females)
2. Sensitization Study:
20 10 males, 10 females)
3. Irritation Controls:
Challenge: 10 (5 males, 5 females)
Sex:
male/female
Details on test animals and environmental conditions:
All animals were checked for viability twice daily. Prior to assignment to study, all animals received a physical examination to ascertain suitability for study,
Currently acceptable practices of good animal husbandry were followed, e.g. , Guide for the Care and use of Laboratory Animals,' NIH Publication No. 85-23, Revised 1985.
Individually in suspended stainless steel cages.
Agway Prolab Guinea-Pig Diet, Ad libitum.
Automatic watering system, Ad libitum,
Municipal Water Supply (Elizabethtown Water Company) ,
There were no known contaminants reasonably expected to be found in food or water which would interfere with the results of this study,
1 . Temperature: monitored and recorded twice daily.
2. Humidity: monitored and recorded daily
3 . Light Cycle: 12 hours light, 12 hours dark (controlled by an automatic timer) .
Each animal was identified with a metal ear tag, bearing a unique number, prior to testing.
Animals were randomly placed in cages upon receipt, and were placed on study as available. Those of questionable health, unacceptable skin or with outlying body weights were not placed on study.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
acetone
Details on exposure:
The hair on the application site (back and sides) was clipped short with an electric clipper on the day prior to each application.
The test material was administered dry and moistened with 0.9% saline.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The test material was applied dry (2 cc/site) , moistened with 0.2 ml of saline, and covered with a Hilltop Chambere . The test site was on the right side of the midline, as close to the midline as possible. The chamber was covered by overlapping, impermeable plastic. This was firmly secured by an elastic adhesive bandage (Elastoplast@) which was wound around the torso of the animal , The chamber was left in place for six hours after which it was removed and the skin was wiped free of any excess material. This was performed once a week, for three weeks, for a total of three exposures.
Duration of treatment / exposure:
This was performed once a week, for three weeks, for a total of three exposures.
Frequency of treatment:
Fourteen days after the last induction exposure, the challenge treatment was administered. The test material was administered in the same manner as in the induction phase, but at a second site, on the left side of the midline. After six hours of exposure, the chambers were removed and the skin wiped free of any excess material with gauze and water.
Doses / concentrations
Dose / conc.:
2 other: cc
Remarks:
The test material was applied dry (2 cc/site) , moistened with 0.2 ml of saline, and covered with a Hilltop Chamber in a volume of 0.2 ml .
No. of animals per sex per dose:
1 . Range-Finding:
6 (3 males, 3 females)
2. Sensitization Study:
20 10 males, 10 females)
3. Irritation Controls:
Challenge: 10 (5 males, 5 females)
Control animals:
yes
Details on study design:
Fourteen days after the last induction exposure, the challenge treatment was administered. The test material was administered in the same manner as in the induction phase, but at a second site, on the left side of the midline. After six hours of exposure, the chambers were removed and the skin wiped free of any excess material with gauze and water.
Positive control:
In order to differentiate dermal reactions produced by irritation from those produced by sensitization, five male and five female animals (previously untreated) were subjected to the same challenge procedures as the animals which received the induction exposures.

Examinations

Observations and examinations performed and frequency:
a. Induction:
Dermal evaluations were made approximately 24 and 48 hours after the first induction exposure to confirm that an appropriate concentration of the test material had been selected.
b, Challenge:
Dermal evaluations were made approximately 24 and 48 hours after the challenge application,
Sacrifice and pathology:
No
Other examinations:
All animals were killed by carbon dioxide inhalation; no post-mortem examinations were performed.
Statistics:
Not specified

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
no effects observed
Mortality:
no mortality observed
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
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined

Effect levels

Key result
Dose descriptor:
dose level:
Effect level:
2 other: cc
Based on:
test mat.
Sex:
male/female
Basis for effect level:
dermal irritation
Remarks on result:
other: No dermal irritation observed.

Target system / organ toxicity

Critical effects observed:
no

Any other information on results incl. tables

A.       Mortality

Al l animals survived throughout the study,

B.       Body Weights (Table I)

All animals gained weight during the study.

      c.       In-life Observations

Al l animals were free of abnormal clinical signs.

      B.       Dermal Responses (Table Il, Summary; Table Ill, Individual Scores)

Animals challenged with the test material (Group IA) exhibited no dermal response at challenge to a non-irritating concentration, as confirmed by a lack of dermal response in irritation control animals (Group 1B) . Therefore, both the incidence and severity indices were O for both the test material treated group and the irritation control group.

Applicant's summary and conclusion

Conclusions:
Under conditions of this study, Ottasept Technical (chloro-3,5-xylenol) exhibited no potential to produce dermal sensitization in guinea pigs