Benzenesulfonic acid, C10-16-alkyl derivs., magnesium salts

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to OECD guidelines to GLP, and therefore meets the requirements for Klimisch code 1.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

(A functional observation battery for neurotoxicity was not performed since this test was not part of the OECD 407 guideline at the time the study was performed)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzenesulfonic acid, mono-C16-24-alkyl derivs., calcium salts

EC Number:

274-263-7

EC Name:

Benzenesulfonic acid, mono-C16-24-alkyl derivs., calcium salts

Cas Number:

70024-69-0

IUPAC Name:

sodium 4-icosylbenzenesulfonate

Test material form:

not specified

Details on test material:

The test material was a direct analog of CAS 70024-69-0 described as C20-24 alkaryl calcium salt derivative.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 41 days
- Weight at study initiation: males, 179-215g; female 141-170g
- Housing: hanging stainless steel wire-bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23°C
- Humidity (%): 48-66%
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Mixed weekly weight/volume in peanut oil

DIET PREPARATION
- Rate of preparation of diet (frequency): weekly

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Chemical analysis of dosing solutions was conducted to confirm that they were homogeneous and met the desired concentrations.

Duration of treatment / exposure:

29 day treatment duration with a 14 day recovery period.

Frequency of treatment:

7 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
gavage doses of 0, 500 or 1000 mg/kg/bw/day
Basis:
actual ingested

No. of animals per sex per dose:

6

Control animals:

yes

Details on study design:

- Dose selection rationale: Data from a pilot two week repeated dose oral study.

Positive control:

No.

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Twice 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:No data

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
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Weekly
- Dose groups that were examined:

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At termination
- Anaesthetic used for blood collection: No
- Animals fasted: Yes
- How many animals: All

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At termination
- Animals fasted: Yes
- How many animals: All

URINALYSIS: Yes
- Time schedule for collection of urine: Overnight before termination
- Metabolism cages used for collection of urine: No
- Animals fasted: Yes

NEUROBEHAVIOURAL EXAMINATION:No
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

Test applied included: parametric ANOVA with Dunnetts post-hoc test, non parametric Kruskal-Wallis and Mann-Whitney U test, Bartletts test for equal variances, Students t test and Dixons test for rejection of outlying values

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

no effects observed

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:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
One animal was sacrificed on Day 0 and one animal was found dead on Day 9, a result of probable misdosing.

Stained fur was observed in high dose animals, scabbed skin occurred in one control male and high dose female displayed sneezing and abnormal respiratory sounds.

BODY WEIGHT AND WEIGHT GAIN
No statistically significant differences were observed in mean bodyweights or bidy weight gains.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
A statistically significant increase in food consumption was observed in low dose males compared with controls.

FOOD EFFICIENCY
No statistically signiificant differences were observed in food efficiency.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
Not recorded.

OPHTHALMOSCOPIC EXAMINATION
Not recorded.

HAEMATOLOGY
Male mean haemoglobin concentrations were significantly decreased with the controls at all dose levels. However, these were not considered to be biologically significant, as there was no dose response trend. A statistically significant increase in partial thromboplastin time was observed in mid and top dose males compared with controls. Prothrombin time was significantly increased in the mid and high dose females during the treatment period, and was significantly reduced in males in the recovery group. This were within normal limits and therefore not considered to be biologically significant. A statistically significant increase in the reticulocyte count was observed in treated males in the recovery group, however, was not considered to be biologically significant.

CLINICAL CHEMISTRY
A statistically significant decrease in serum cholesterol was observed in high dose males and females and persisted in females into the recovery period. This are considered to eb treatment related.

Statistically significant inreases were observed in alaninine aminotransferase, lactic dehydrogenase, aspartate aminotransferase, sodium, phosphorus and triglycerides were observed as well as decreases in albumin and chloride. There was no dose related trend with these changes, therefore they are not considered to be treatment related.

URINALYSIS
A statistically significant increase in specific gravity was observed in low dose males. Urine volume was significantly reduced in treated males in the recovery group. This was not considered to be biologically significant.

NEUROBEHAVIOUR
Not recorded.

ORGAN WEIGHTS
No statistically signoficant differences were observed.

GROSS PATHOLOGY
No substance related macroscopic changes were observed.

HISTOPATHOLOGY: NON-NEOPLASTIC
No substance related microscopic changes were observed.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
Not recorded.

HISTORICAL CONTROL DATA (if applicable)
Not recorded.

Effect levels

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Mean serum cholesterol levels were significantly reduced in the 1000 mg/kg males and females at termination of dosing. This was still significantly reduced in 1000 mg/kg females at the end of the 14 day recovery period.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1: Average body weights and body weight gains during xx days of treatment

Dose rate (ppm)	Body Weights (g)					Total Weight Gain
	Week 0	Week 1	Week 2	Week 3	Week 4	g	% of control
Male
0	195	243	286	323	352	157	181
100	196	245	298	340	374	175	191
500	200	245	289	329	362	162	181
1000	193	240	283	315	346	154	179
Female
0	155	175	194	213	223	67	144
100	156	174	194	215	228	72	146
500	154	175	190	212	221	67	144
1000	155	174	195	212	224	69	145

 

Applicant's summary and conclusion

Conclusions:

A NOAEL of 500 mg/kg bw/day was identified in this study.

Executive summary:

In a subchronic toxicity study calcium sulphonate was administered to 12 Sprague-Dawley rats/sex/dose in the control and top dose groups and 6 animals Sprague-Dawley rats/sex/dose in the low and med dose via gavage at dose levels of 0, 100, 500 or 1000 mg/kg bw/day.

A decrease in serum cholesterol levels occurred in the top dose group. The LOAEL is 1000 mg/kg bw/day, based on a decrease in serum cholesterol at the top dose. The NOAEL is 500 mg/kg bw/day.

This subchronic toxicity study in the rat is acceptable and satisfies the guideline for a subchronic oral study (OPPTS 870.3100: OECD 480) in rats.