Toluene-4-sulphonic acid

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

other: Read across from a member of the Hydrotropes category

Adequacy of study:

weight of evidence

Study period:

July 20-August 6, 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

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.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)

Deviations:

yes

Remarks:

17 day exposure

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium (xylenes and 4-ethylbenzene) sulfonates

EC Number:

701-037-1

Molecular formula:

-

IUPAC Name:

Sodium (xylenes and 4-ethylbenzene) sulfonates

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: 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 / 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: 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 delivered average daily doses of approximately 10, 30, 90, 260 and 800 mg/kg bw for males and 13, 40, 120, 330, and 1,030 mg/kg to females.
- 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

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Remarks:

Control for males and females

Doses / concentrations 2

Dose / conc.:

10 mg/kg bw/day

Remarks:

Based on active ingredient, males

Doses / concentrations 3

Dose / conc.:

30 mg/kg bw/day

Remarks:

Based on active ingredient, males

Doses / concentrations 4

Dose / conc.:

90 mg/kg bw/day

Remarks:

Based on active ingredient, males

Doses / concentrations 5

Dose / conc.:

260 mg/kg bw/day

Remarks:

Based on active ingredient, males

Doses / concentrations 6

Dose / conc.:

800 mg/kg bw/day

Remarks:

Based on active ingredient, males

Doses / concentrations 7

Dose / conc.:

13 mg/kg bw/day

Remarks:

Based on active ingredient, females

Doses / concentrations 8

Dose / conc.:

40 mg/kg bw/day

Remarks:

Based on active ingredient, females

Doses / concentrations 9

Dose / conc.:

120 mg/kg bw/day

Remarks:

Based on active ingredient, females

Doses / concentrations 10

Dose / conc.:

330 mg/kg bw/day

Remarks:

Based on active ingredient, females

Doses / concentrations 11

Dose / conc.:

1 030 mg/kg bw/day

Remarks:

Based on active ingredient, females

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: 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: 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

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, A necropsy was performed on all animals. The heart, right kidney, liver, lungs, right testis, and thymus were weighed.
HISTOPATHOLOGY: Yes, Histopathologic examination was restricted to skin from the site of application, skin from an untreated site, and gross lesions.

Statistics:

Kaplan-Meier method

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

Only tan or brown discoloration of the skin and crusty white deposits at the application site.
In males and females, the few skin lesions observed grossly and microscopically were generally attributed to repeated clipping and were not considered related to chemical administration.

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

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Other effects:

not specified

Details on results:

CLINICAL SIGNS: only tan or brown discoloration of the skin and crusty white deposits at the application site.
In males and females, the few skin lesions observed grossly and microscopically were generally attributed to repeated clipping and were not considered related to chemical administration.
MORTALITY - no mortality
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 not to be of toxicological relevance.
GROSS PATHOLOGY - no treatment related effects
HISTOPATHOLOGY:
NON-NEOPLASTIC - no treatment related effects

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 030 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

female

Basis for effect level:

body weight and weight gain

clinical signs

food consumption and compound intake

gross pathology

mortality

organ weights and organ / body weight ratios

2

Key result

Dose descriptor:

NOAEL

Effect level:

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

Based on:

act. ingr.

Sex:

male

Basis for effect level:

body weight and weight gain

clinical signs

gross pathology

mortality

organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

See attached tables for results details.

Applicant's summary and conclusion

Conclusions:

NOAEL > 1030 mg active ingredient/kg bw female
NOAEL > 800 mg active ingredient/kg bw male

Executive summary:

The repeated dermal toxicity of Sodium (xylenes and 4-ethylbenzene) sulfonates was assessed following official guideline EPA OPP 82-2 (Repeated dose dermal toxicity -21/28 days). There was a deviation due to the reduced administration period which was of 17 days. The test was perfomed on rats and the results showed no mortality, clinical signs only revelaed tan or brown discoloration of the skin and crusty white deposits at the application site. In males and females, the few skin lesions observed grossly and microscopically were generally attributed to repeated clipping and were not considered related to chemical administration.