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Toxicological information

Repeated dose toxicity: oral

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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:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity 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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 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.