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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
July 20-August 6, 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Protocols and resuls reviewed and accepted by the National Toxicology Program's Board of Scientific Counselor's Technical Reports Review Subcommittee, USA National Institutes of Health. The study was used as dose finding study for a carcinogenicity study and therefore the number of endpoints was limited.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)
Deviations:
yes
Remarks:
17 day only
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): sodium xylene sulfonate
- Molecular formula (if other than submission substance): no data
- Molecular weight (if other than submission substance): no data
- Substance type: organic
- Physical state: powder
- Analytical purity: 65%
- Impurities (identity and concentrations): not identified from NMR spectrum provided
- Composition of test material, percentage of components: 11.5% ortho, 38% meta, 15.5% para
- Purity test date: February 13, 1986
- Lot/batch No.: RO92085 / 03
- Expiration date of the lot/batch: no data
- Stability under test conditions: stable
- Storage condition of test material: glass bottles with Teflon lined caps or double bagged in metal drums at room temperature in the dark
- Other:

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms, Germantown, NY
- Age at study initiation: 5 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: 1 animal per cage; polycarbonate cage on stainless steel racks with heat-treated hardwood chips and spun-bonded polyester filters; changed once per week
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5 to 25.6
- Humidity (%): 51 to 68
- Air changes (per hr): 10 minimum
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: July 20 To: August 6, 1987

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on exposure:
TEST SITE
- Area of exposure: clipped interscapular skin
- % coverage: no data
- Type of wrap if used: no data
- Time intervals for shavings or clipplings: once


REMOVAL OF TEST SUBSTANCE
- Washing (if done): not washed


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 300 microliters applied five days per week
- Concentration (if solution): 0, 5, 15, 44, 133 and 400 mg/mL
- Constant volume or concentration used: yes


VEHICLE
- Justification for use and choice of vehicle (if other than water): distilled water


USE OF RESTRAINERS FOR PREVENTING INGESTION: no data
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
doses analyzed by HPLC at the start of the 17 day period
Duration of treatment / exposure:
17 days
Frequency of treatment:
5 days per week
Doses / concentrations
Remarks:
Doses / Concentrations:
10, 30, 90, 260 and 800 mg active ingredient/kg bw for males, and 13, 40, 120, 330 and 1030 mg active ingredient/kg bw for females
Basis:
analytical per unit body weight
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: wide range for screening purposes
- Rationale for animal assignment (if not random): random
Positive control:
no data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily


DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: twice daily


BODY WEIGHT: Yes
- Time schedule for examinations: days 1, 8 and 17


FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No


WATER CONSUMPTION: No


OPHTHALMOSCOPIC EXAMINATION: No


HAEMATOLOGY: No


CLINICAL CHEMISTRY: No


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No



OTHER:
Sacrifice and pathology:
GROSS PATHOLOGY: Yes (Table F1)
HISTOPATHOLOGY: Yes
Statistics:
Kaplan-Meier method

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects 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
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY - no mortality; only tan or brown discoloration of the skin and crusty white deposits at the application site




BODY WEIGHT AND WEIGHT GAIN - no treatment effects


ORGAN WEIGHTS - increase in liver weights relative to body weight in males and females at two highest doses; considered to be of unknown toxicological relevance


GROSS PATHOLOGY - no treatment related effects


HISTOPATHOLOGY: NON-NEOPLASTIC - no treatment related effects


Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 1 030 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: overall effects clinical signs; mortality; body weight; gross pathology; organ weights; histopathology

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL = highest dose (1030 mg active ingredient/kg bw).