Sodium cumenesulphonate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

other: published data

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)

Deviations:

yes

Remarks:

As per OECD 411 with the exception of clinical signs recorded weekly, no food consumption, no ophthalmoscopy, clinical

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium xylenesulphonate

EC Number:

215-090-9

EC Name:

Sodium xylenesulphonate

Cas Number:

1300-72-7

Molecular formula:

C8H10O3S.Na

IUPAC Name:

sodium xylenesulphonate

Test material form:

solid

Specific details on test material used for the study:

CAS Number: 1300-72-7
Identity: Xylene sulfonic acid, sodium salt
Purity: 65%
Remarks: purity 65% (11.5% ortho, 38% meta and 15.5% para).

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Taconic Farms, Germantown, NY
- Age at study initiation: 6 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: 1 animal per cage; polycarbonate cage with stainless steel rack (rotated every 2 weeks); heat-treated hardwood chips and spun-bonded polyester cage filters changed weekly
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 to 24.5
- Humidity (%): 20 to 67
- Air changes (per hr): 10 minimum
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:

occlusive

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): 300 microliters
- Concentration (if solution): 0, 5, 15, 44, 133, 400 mg/mL
- Constant volume or concentration used: yes


VEHICLE
- Justification for use and choice of vehicle (if other than water): ethanol because test material beads up rather than spreads out when applied neat
- Amount(s) applied (volume or weight with unit): 300 microliters of combined test material and vehicle
- Concentration (if solution): 50% solution of ethanol i water
- Lot/batch no. (if required): no data
- Purity: no data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

HPLC on each dose at beginning, middle and end of the study

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

5 days per week

Doses / concentrations

Remarks:

Doses / Concentrations:
5, 15, 44, 133 and 400 mg/ml (vehicle 50% ethanol, volume applied 0.3 ml) which averaged approximately 6, 20, 60, 170 and 500 mg a.i./kg for males and
10, 30, 90, 260 and 800 mg a.i./kg for females taking into consideration the 65% purity of the substance; solutions/suspensions were prepared every 2
weeks; feeding ad libitum.

No. of animals per sex per dose:

10

Control animals:

yes, concurrent no treatment

Details on study design:

Dose selection rationale: wide range of doses for screening
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: 10 males and 10 females at each dose for special hematology and clinical chemistry study
- Post-exposure recovery period in satellite groups: no data
- Section schedule rationale (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 checked in table were not included.


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: Yes
- Time schedule for collection of blood: day 5 and 21 (from satellite group) and at end of study for all animals
- Anaesthetic used for blood collection: Yes / carbon dioxide
- Animals fasted: No data
- How many animals: 10 per dose; males and females
- Parameters checked in table [No.1] were examined.


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 5 and 21 (from satellite group) and at end of study for all animals
- Animals fasted: No data
- How many animals: 10 per dose; males and females
- Parameters checked in table [No.1] were examined.


URINALYSIS: No


NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

Kaplan-Meier method

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 specified

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological 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 treatment related effects

BODY WEIGHT AND WEIGHT GAIN - no treatment related effects


FOOD CONSUMPTION - protocol indicates measurements conducted, but not reported


HAEMATOLOGY - no treatment related effects


CLINICAL CHEMISTRY - no treatment related effects


ORGAN WEIGHTS - decrease seen in liver weights of males but not accompanied by histopathology changes; a liver enzyme increase was observed in males at day 5 but not at a later time period.


GROSS PATHOLOGY - no treatment related effects


HISTOPATHOLOGY: NON-NEOPLASTIC - protocol indicates examinations conducted, but not reported


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

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 800 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

female

Basis for effect level:

other: other: overall effects: other: epidermal hyperplasia at highest dose in males

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Results
Value: NOAEL = 400 mg/ml which equals 800 mg/kg bw active ingredient (a.i.)
NOAEL = (800 mg active ingredient/kg bw).

Executive summary:

Results

Value: NOAEL = 400 mg/ml which equals 800 mg/kg bw active ingredient (a.i.)

NOAEL = (800 mg active ingredient/kg bw).