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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:
experimental study
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 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 22.5 to 25.6- Humidity (%): 51 to 68- Air changes (per hr): 10 minimum- Photoperiod (hrs dark / hrs light): 12 / 12IN-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: onceREMOVAL OF TEST SUBSTANCE- Washing (if done): not washedTEST 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: yesVEHICLE- Justification for use and choice of vehicle (if other than water): distilled waterUSE 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 femalesBasis: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: NoDETAILED CLINICAL OBSERVATIONS: Yes- Time schedule: twice dailyDERMAL IRRITATION (if dermal study): Yes - Time schedule for examinations: twice dailyBODY WEIGHT: Yes- Time schedule for examinations: days 1, 8 and 17FOOD CONSUMPTION: - Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No dataFOOD 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: NoWATER CONSUMPTION: NoOPHTHALMOSCOPIC EXAMINATION: NoHAEMATOLOGY: NoCLINICAL CHEMISTRY: No URINALYSIS: NoNEUROBEHAVIOURAL EXAMINATION: NoOTHER:
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 siteBODY WEIGHT AND WEIGHT GAIN - no treatment effectsORGAN WEIGHTS - increase in liver weights relative to body weight in males and females at two highest doses; considered to be of unknown toxicological relevanceGROSS PATHOLOGY - no treatment related effectsHISTOPATHOLOGY: NON-NEOPLASTIC - no treatment related effects

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
>= 1 030 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: overall effectsclinical 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).