Benzenesulfonic acid, 4-(1-methylethyl)-, potassium salt (1:1)

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

other: Read across from another member of the category

Adequacy of study:

key study

Study period:

October 8, 1979 to January 7, 1980

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:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

Resembles OECD 408; young male and female rats (10 per sex per dose) exposed by diet for 13 weeks; 5 exposure levels and a control; analytical verification of test substance in feed; ad libitum feed; survival, body weight, feed consumption, gross and histopathology examined.

GLP compliance:

no

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: Charles River Breeding Labs
- Age at study initiation: no data
- Weight at study initiation: 144-177 g males, 115-144 g females
- Fasting period before study: no data
- Housing: five per cage in polycarbonate cages suspende in stainless steel racks covered with spun bonded fiberglass filter sheets which were vacumed daily and changed once a month.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 1
- Humidity (%): no data
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12
IN-LIFE DATES: From: October 8, 1979 To: January 7, 1980

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: test substance mixed with feed bi-weekly using a 16 quart stainless steel PK blender

DIET PREPARATION
- Rate of preparation of diet (frequency): biweekly
- Mixing appropriate amounts with (Type of food): Purina mash
- Storage temperature of food: no data

VEHICLE
- Justification for use and choice of vehicle (if other than water): no vehicle

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Analysis of test substance in the feed was performed once during the study at all dosing levels

Duration of treatment / exposure:

91 days

Frequency of treatment:

ad libitum in feed

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.125 mg/kg bw/day (nominal)

Remarks:

Basis:nominal in diet

Doses / concentrations 2

Dose / conc.:

0.25 other: %

Remarks:

Basis:nominal in diet

Doses / concentrations 3

Dose / conc.:

0.5 other: %

Remarks:

Basis:nominal in diet

Doses / concentrations 4

Dose / conc.:

1 other: %

Remarks:

Basis:nominal in diet

Doses / concentrations 5

Dose / conc.:

2 other: %

Remarks:

Basis:nominal in diet

No. of animals per sex per dose:

10

Control animals:

yes, concurrent no treatment

Details on study design:

- Dose selection rationale: preliminary range finding study- Rationale for animal assignment (if not random): random

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
Time schedule: twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: at test initiation and then weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

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 AND COMPOUND INTAKE (if drinking water study): No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (Attachment B "signed copy of Dr. Brown's pathology r eport" not reviewed)HISTOPATHOLOGY: Yes (Attachment B "signed copy of Dr. Brown's pathology report" not reviewed)

Other examinations:

Murine Virus determination for five control rats per sex upon completion of the test

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

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:

not examined

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 - 5 of 10 animals died at 4% dose level, 1 of 10 died at 1% dose level; no clinical signs of toxicity at any dose level

BODY WEIGHT AND WEIGHT GAIN - limited at 2% and 4%

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study) - animals refusing their food at 2% and 4%

GROSS PATHOLOGY - no gross lesions

HISTOPATHOLOGY: NON-NEOPLASTIC - no microscopic lesions

OTHER FINDINGS - no murine virus titers

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 - < 2 other: % in diet

Sex:

male/female

Basis for effect level:

other: overall effectsmortality; body weight

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

This study was conducted to establish doses for a chronic study. The recommendation is MTD = 4% and MTD/2 = 2% for the chronic study.

Applicant's summary and conclusion

Conclusions:

NOAEL > 1 < 2% in diet

Executive summary:

The repeated oral toxicity of Sodium (xylenes and 4-ethylbenzene) sulfonates was assessed following official guideline OECD 408, Repeated Dose 90-Day Oral Toxicity Study in Rodents. The test results showed mortality, effects on body weight, no lesions in gross pathology and histopathology.