Sulfonic acids, petroleum, calcium salts

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Between 18 April 2002 and 31 May 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to OECD guidelines and to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

115733-09-0

Cas Number:

115733-09-0

IUPAC Name:

115733-09-0

Constituent 2

Reference substance name:

Benzenesulfonic Acid, C14-24-Branched And Linear Alkyl Derivs., Calcium Salts

IUPAC Name:

Benzenesulfonic Acid, C14-24-Branched And Linear Alkyl Derivs., Calcium Salts

Details on test material:

The substance is structurally analogous to the EC 274-263-7 and includes all chain lengths in the registered substance.

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
- Housing: individuall;y in suspended stainless stell wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50, 150, 500 and 1000 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Dosage levels were selected by the sponsor based on available data from previous studies.
- Rationale for animal assignment (if not random): Random
- Post-exposure recovery period in satellite groups: 14 days
- Section schedule rationale (if not random): Random

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice daily


BODY WEIGHT: Yes
- Time schedule for examinations: 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


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
- Time schedule for examinations:


OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Days 25 and 38
- Dose groups that were examined: All


HAEMATOLOGY: Yes
- Time schedule for collection of blood: On sacrifice
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes
- How many animals: All



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


URINALYSIS: Yes
- Time schedule for collection of urine: Overnight prior to sacrifice
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes


NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Abbreviated battery on weeks 1 and 2. Full battery on weeks 3 and 5
- Dose groups that were examined: All
- Battery of functions tested: sensory activity / grip strength / motor activity

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

Parametric and count data were analyzed by One-Way analysis of Variance (ANOVA). If significance was detected, pair-wise group comparisons proceeded using the Tukey-Kramer test. Ranked data were analysed by Kruskall Wallis non-parametric ANOVA, followed by Dunn's test. Descriptive and quanta data were analyzed by fisher's Exact test. Group by group comparison was undertaken using the Chi-Square test.

Abolute and relative organ weights and clinical pathology data were analyzed for homogeneity of variance using Levene's test, then Kruskal-Wallis non-parametric ANOVA, followed by Dunn's test.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

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:

no effects observed

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
No mortality or significant clinical abnormalities were observed during the main or recovery phases of this study.

BODY WEIGHT AND WEIGHT GAIN
In the males, a statistically significant decreased bodyweight gain was observed in the top dose group. A decrease in bodyweight gain (not statistically significant) was obsreved in the next highest dose group. However, these decreases were less than 10%., and therefore of questionable statistical significance.

In females, no statistically significant changes were observed.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Statistically significant decreases in food consumption occurred in the second highest group males and the top dose group females.

FOOD EFFICIENCY
Not recorded.

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

OPHTHALMOSCOPIC EXAMINATION
No treatment related effects occurred.

HAEMATOLOGY
No biologically significant changes occurred.

CLINICAL CHEMISTRY
No biologically significant changes occurred.

URINALYSIS
No biologically significant changes occurred.

NEUROBEHAVIOUR
No biologically significant changes occurred.

ORGAN WEIGHTS
No biologically significant changes occurred.

GROSS PATHOLOGY
No adverse gross pathology occurred in treated animals.

HISTOPATHOLOGY: NON-NEOPLASTIC
irritation of the non-glandular stomach occurred in the two highest dose group males and the three highest dose group females.This irritation appeared to be transient. Minimal oedema in the submucosa was observed in the second highest dose group males and minimal to mild oedema in the submucosa nad minimal epithelial hyperplasia was observed in the highest dose group males. However, these effects were not observed after the reovery phase.

Minimal oedema in the submucosa, minimal haemhorrage, minimal epithelial hyperplasia, mild inflammation and a mild ulcer occurred in females in the second highest dose group. Minimal oedema in the submucosa and minimal to mild epithelial hyperplasia was observed in females in the top dose group.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
Not recorded.

HISTORICAL CONTROL DATA (if applicable)
Not recorded.

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

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 28 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	268	302	331	358	372	104	139
50	268	303	335	359	373	105	139
150	267	301	330	360	370	103	139
500	263	290	312	327	340	77	129
1000	267	298	324	340	351	83	131
Female
0	186	203	216	228	263	50	141
50	186	206	222	235	239	53	128
150	184	199	214	223	235	50	128
500	187	202	212	224	228	41	122
1000	184	202	211	226	229	45	125

 

Applicant's summary and conclusion

Conclusions:

A NOAEL of 1000 mg/kg bw/day was identified in this study.

Executive summary:

In a subchronic toxicity study was administered to 5 Sprague-Dawley rats/sex/dose via gavage at dose levels of 0, 50, 150, 500, or 1000 mg/kg bw/day).

 

No dose related effects occurred. The NOAEL is 1000 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.