Benzenesulfonic acid, C14-24-alkyl derivatives, magnesium salts, overbased

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to OECD guidelines to to GLP, and therefore meets the requirements for Klimisch code 1. Study is classified as Klimisch code 2 only because it is based on read across.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

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 fuctional observation battery for neurotoxicity was not performed since this test was not par of the OECD 407 guideline at the time the study was performed

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

analog 70024-69-0

IUPAC Name:

analog 70024-69-0

Constituent 2

Reference substance name:

analog EC 274-263-7

IUPAC Name:

analog EC 274-263-7

Details on test material:

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

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

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.

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, 100, 500 or 1000 mg/kg/bw
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.

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

Tests applied included; parametric ANOVA with Dunnetts post-hoc test, non parametric Kruskal-Walls 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, result of probable misdosing.

Effect levels

Key result

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 cholestrol 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 29 days of treatment

 

Dose rate (mg/kg	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	N/A
100	196	245	298	340	374	178	111
500	200	245	289	329	362	162	103
1000	193	240	283	315	346	153	97
Female
0	155	175	194	213	223	68	N/A
100	156	174	194	215	228	72	106
500	154	175	190	212	221	67	99
1000	155	174	195	212	224	69	101

 

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 mod 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 requirement for a subchronic oral study (OPPTS 870.3100; OECD 408) in rats.