Sodium diisopropylnaphthalenesulphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 2001

Deviations:

yes

Remarks:

The study plan deviation is considered not to have affected the integrity of the study

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

yes

Remarks:

The study plan deviation is considered not to have affected the integrity of the study

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

2008

Deviations:

yes

Remarks:

The study plan deviation is considered not to have affected the integrity of the study

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines

Version / remarks:

2000, including the most recent revisions

Deviations:

yes

Remarks:

The study plan deviation is considered not to have affected the integrity of the study

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium diisopropylnaphthalenesulphonate

EC Number:

215-343-3

EC Name:

Sodium diisopropylnaphthalenesulphonate

Cas Number:

1322-93-6

Molecular formula:

C16H20O3S.Na

IUPAC Name:

sodium diisopropylnaphthalene-sulfonate

Test material form:

solid: particulate/powder

Details on test material:

white to off-white lumps

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Han, Outbred, SPF-Quality

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx. 9-11 weeks
- Weight at study initiation: 142-181 g
- Fasting period before study:
Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available.
- Housing:
On arrival and following assignment to the study, animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. The room(s) in which the animals were kept were documented in the study records.
Animals were separated during designated procedures/activities. Each cage was clearly labeled.
- Diet (e.g. ad libitum):
Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures.
The feed was analyzed by the supplier for nutritional components and environmental contaminants. Results of the analysis were provided by the supplier and are on file at the Test Facility.
It is considered that there were no known contaminants in the feed that would interfere with the objectives of the study.
- Water (e.g. ad libitum):
Municipal tap-water was freely available to each animal via water bottles.
Periodic analysis of the water was performed, and results of these analyses are on file at the Test Facility.
It is considered that there were no known contaminants in the water that would interfere with the objectives of the study.
- Acclimation period:
The animals were allowed to acclimate to the Test Facility toxicology accommodation for at least 5 days before the commencement of dosing.

ENVIRONMENTAL CONDITIONS
Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were maintained. The actual daily mean temperature during the study period was 20-21°C with an actual daily mean relative humidity of 40 to 51%. A 12-hour light/12-hour dark cycle was maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Elix, supplier: Millipore S.A.S., Molsheim, France

Details on oral exposure:

VEHICLE
- Concentration in vehicle / Amount of vehicle (if gavage):
The dose volume for each animal was based on the body weight measurement prior to dosing. A dose volume of 10 mL/kg body weight was used for each dose.
- Justification for choice of vehicle:
Trial preparations were performed to select the suitable vehicle and to establish a suitable formulation procedure. These trials were not performed as part of this study and these preparations were not used for dosing. Raw Data of these trials will be retained by the Test Facility.

DOSAGE PREPARATION (if unusual):
Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements.
The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing.
No adjustment was made for specific gravity of the vehicle. No correction was made for the purity/composition of the test item.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
The oral route was selected as it is a possible route of human exposure during manufacture, handling or use of the test item.
The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days.
Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

The oral LD50 value of the test item was ranked within the following ranges: 0-5, 5-50, 50-300 or 300-2000 mg/kg b.w. or as exceeding 2000 mg/kg b.w. The LD50 cut-off value was established based on OECD guideline 423. No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg two females were found dead between days 1 and 2 post-treatment. No further mortality occurred.

Clinical signs:

other: At 2000 mg/kg, hunched posture, salivation, piloerection, uncoordinated movements, labored respiration, gasping and/or chromodacryorrhoea were noted for the animals between Days 1 and 6. At 300 mg/kg, hunched posture, piloerection, uncoordinated moveme

Gross pathology:

Abnormalities of the stomach, duodenum and jejunum (contents gelatinous) were found in the animals that died during the study, at macroscopic post mortem examination. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 value of CH04207 in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight.
Based on these results:
• according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments), CH04207 should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.
• according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), CH04207 should be classified as Category 4 and should be labeled as H302: Harmful if swallowed.

Executive summary:

The objective of this study was todetermine the potential toxicity of CH04207, when given by oral gavage at a single dose to rats of a single sex at one or more defined doses to evaluate the potential reversibility of any findings.

The study was carried out in compliance with the guidelines described in:

·      OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

·      EC No 440/2008, part B: "Acute Oral Toxicity, Acute Toxic Class Method"

·      EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

·      JMAFF Guidelines (2000), including the most recent revisions.

Initially, CH04207 was administered by oral gavage to three female Wistar rats at 300 mg/kg body weight. In a stepwise procedure two additional groups of three femaleswere dosed at 300 and 2000 mg/kg body weight . All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

At 2000 mg/kg, two out of three animals were found dead on Day 1 and/or 2, no further mortality occurred. At 300 mg/kg, no mortality occurred.

At 2000 mg/kg, hunched posture, salivation, piloerection, uncoordinated movements, labored respiration, gasping and/or chromodacryorrhoea were noted for the animals between Days 1 and 6. At 300 mg/kg, hunched posture, piloerection, uncoordinated movements, salivation and/or rales were noted for the animals between Days 1 and 2.

The mean body weight gain shown by the surviving animals over the study period was considered to be normal.

Contents of the stomach, duodenum and jejunum appeared gelatinous in the animals that died during the study, at macroscopic post mortem examination. Macroscopic examination of the surviving animals at termination did not reveal any abnormalities.

 

The oral LD50 value of CH04207 in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight.

Based on these results:

·      harmful if swallowed (Category 4) for acute toxicity by the oral route.

·      Harmful if swallowed.