Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: dermal
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
February 23 - May 26, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Protocols and results 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:
OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
clinical signs reported weekly; no food consumption; no ophthalmoscopy, no clinical chemisty; no haematology
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms, Germantown, NY
- Age at study initiation: 7 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: 1 animal per cage; polycarbonate cages and stainless steel racks (rotated every 2 weeks), with heat-treatted hardwood chip bedding and spun-bonded polyester cage filters changed every week.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 19 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 to 23.9
- Humidity (%): 15 to 63
- Air changes (per hr): 10 minimum
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: February 23 To: May 26, 1988

Administration / exposure

Type of coverage:
not specified
Vehicle:
ethanol
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 at start of study


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 microliters
- 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): ethanol, because in water alone the test substance beaded up
- Amount(s) applied (volume or weight with unit): 100 microliters of 50% ethanol and 50% distilled water
- Concentration (if solution): 50%
- Lot/batch no. (if required): no data
- Purity: no data


USE OF RESTRAINERS FOR PREVENTING INGESTION: no data
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
HPLC verification of each dose at beginning, midpoint and end of study
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
5 days per week
Doses / concentrations
Remarks:
Doses / Concentrations:
17, 50, 140, 440 and 1300 mg active ingredient/kg bw for males and 20, 60, 170, 540 and 1620 mg active ingredient/kg bw for females
Basis:
analytical per unit body weight
No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: wide range for screening study
- Rationale for animal assignment (if not random): random
Positive control:
no data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations were not included in the report.


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly


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


BODY WEIGHT: Yes
- Time schedule for examinations: weekly


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


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
HISTOPATHOLOGY: Yes
Statistics:
Kaplan and Meier

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
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:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY - no treatment related effects


BODY WEIGHT AND WEIGHT GAIN - slight increase in body weight of males at highest dose


ORGAN WEIGHTS - increase in kidney weight of males but not dose dependent


GROSS PATHOLOGY - no treatment related effects


OTHER FINDINGS - epidermal hyperplasia of application site in males and females at the highest dose

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 440 mg/kg bw (total dose)
Sex:
male
Basis for effect level:
other: overall effects other: epidermal hyperplasia (also seen in females at highest dose)

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL = 440 mg a.i./kg bw