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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:
read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Study conducted to OECD guidelines to to GLP, and therefore meets the requirements for Klimisch code 1. However as this study is used in the context of a read across, Klimisch 2 is assigned.
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH
1. HYPOTHESIS FOR THE CATEGORY APPROACH
The read across follows Scenario 5 - Qualitatively and quantitatively similar effects are caused by a common compound, which is formed from all category members (as described in the 2017 Read-Across Assessment Framework document).
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
TARGET: Benzenesulfonic acid, di-C10-14-alkyl derivs., sodium salts
SOURCE: Sodium 4-icosylbenzenesulfonate
3. CATEGORY APPROACH JUSTIFICATION
Linear and non-linear or branched alkylbenzene sulfonates are anionic surfactants with molecules characterized by a hydrophobic (apolar) and a hydrophilic (polar) group. As a group of chemicals, they are generally mixtures of closely related isomers and homologues. Each molecule contains an aromatic ring sulfonated at the para position and attached to either a linear or a branched alkyl chain at any position except the terminal carbons. The sulfonate group is a common functional group present in each of the category members, and is expected to exhibit similar biological activities with little influence from the length of carbon chain. The cation components of the chemicals (e.g. calcium, magnesium, sodium, or barium) are not expected to contribute significantly to the toxicity.
4. DATA MATRIX
See Read Across document attached to CSR

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
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 part of the OECD 407 guideline at the time the study was performed
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 derivative.

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
- 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg-bw day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
100 mg/kg-bw day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
500 mg/kg-bw day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
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:
Tests 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 body 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 significant differences were observed in food efficiency.

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

OPHTHALMOSCOPIC EXAMINATION
Not recorded

HAEMATOLOGY
Male mean cell haemoglobin concentrations were significantly decreased compared 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 was considered to be treatment related.

Statistically significant increases were observed in alanine aminotransferase, lactic dehydrogenase, aspartate aminotransferase, sodium, phosphorus and triglycerides, 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 significant 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)
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 rats/sex in the control and top dose and 6 rats/sex in the low and mid 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.