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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
2016-10-21 to 2016-12-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
See chapter 13 for support for read-across within the category of Alkyl Naphthalene Sulfonates (ANS).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
(Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany)
Test type:
acute toxic class method

Test material

Constituent 1
Chemical structure
Reference substance name:
Naphthalenesulfonic acid, bis(1-methylethyl)-, Me derivs., sodium salts
EC Number:
272-715-8
EC Name:
Naphthalenesulfonic acid, bis(1-methylethyl)-, Me derivs., sodium salts
Cas Number:
68909-82-0
Molecular formula:
UVCB substance
IUPAC Name:
Aromatic hydrocarbons, C10-13, reaction products with isopropylalcohol, sulphonated, sodium salts
Test material form:
solid: granular
Details on test material:
Name: Naphthalenesulfonic acid, bis(1-methylethyl)-, methyl derivs., sodium salt
Product: MORWET IP Powder
Chemical Name: Naphthalenesulfonic acid, bis(1-methylethyl)-, methyl derivs., sodium salt
CAS No.: 68909-82-0
Batch No.: 1452486
Physical State: solid, powder
Colour: tan
pH: 7.5 to 10 in 5 % solution
Active Components: UVCB substance with 100% purity
Average molecular weight: 346 g/mol (range from 213-474 g/mol)
Purity: 100 %
Storage Conditions: room temperature
Expiry Date: 07 June 2021
Safety Precautions: The routine hygienic procedures were sufficient to assure personnel health and safety.
Specific details on test material used for the study:
Name: Naphthalenesulfonic acid, bis(1-methylethyl)-, methyl derivs., sodium salt
CAS No.: 68909-82-0
Batch No.: 1452486
Physical State: powder
Colour: tan
pH Value: 7.5 – 10 in 5% solution
Purity: 100%
Expiry Date: 07 June 2021
Storage Conditions: at room temperature
Safety Precautions: The routine hygienic procedures were sufficient to assure personnel health and safety.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Housing and Feeding Conditions
- Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Certificates of food, water and bedding are filed for two years at BSL Munich and afterwards archived at Eurofins Munich
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Aqua ad injectionem (AlleMan Pharma, lot no. 605070, expiry date: 04/2019)
Details on oral exposure:
The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.
The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 10 mL/kg body weight.

Doses:
The starting dose was selected to be 2000 mg/kg body weight. Compound related mortality was recorded for 3 animals of step 1. Based on these results and according to the acute toxic class method regime, a second step was performed at a dose of 300 mg/kg body weight. No compound related mortality was recorded for any animal of step 2. Based on these results and according to the acute toxic class method regime, a third step was performed at a dose of 300 mg/kg body weight. No compound-related mortality was recorded for any animal of step 3. Based on these results and according to the acute toxic class method regime no further testing was required.
No. of animals per sex per dose:
3 per step (3 steps performed)
Control animals:
no
Details on study design:
The surviving animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.
Weight Assessment
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
Clinical Examination
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Pathology
The animals which were found dead during the observation period were necropsied at retrieval.
At the end of the observation period the surviving animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally at a dosage of 250-400 mg/kg bw.
All animals were subjected to gross necropsy. All gross pathological changes were recorded and the tissues were preserved for a possible histopathological evaluation. The preserved tissues of which no histopathological evaluation was made will be discarded 3 months after the release of the final report unless otherwise agreed upon with the sponsor.
Evaluation of Results
Results were interpreted according to OECD Guideline 423, Annex 2 and GHS.
Individual reactions of each animal were recorded at each time of observation.
Toxic response data were recorded by dose level.
Nature, severity and duration of clinical observations were described.
The body weight changes were summarised in a tabular form.
Necropsy findings were described.

Statistics:
According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the
results is not regarded as necessary.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
ca. 500 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: Limit dose testd: 2000 mg/kg body weight
Mortality:
All animals treated with the test item at a dose of 2000 mg/kg were found dead on test day 1. All remaining animals survived until the end of the study without showing any signs of toxicity.
Clinical signs:
The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, prone position, hunched posture, piloerection and half eyelid-closure.
Body weight:
Throughout the 14-day observation period, the weight gain of the surviving animals was within the normal range of variation for this strain.
Gross pathology:
Macroscopic findings of surviving animals:
At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.
Macroscopic findings of animals not having survived until the end of the observation period:
Necropsy revealed blood in parts of the gastrointestinal tract.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of the present study, the median lethal dose of Naphthalenesulfonic acid, bis(1-methylethyl)-, methyl derivs., sodium salt after a single oral administration to female rats, observed over a period of 14 days is 500 mg/ kg bw (LD50 cut-off).
Executive summary:

Summary Results

One group of three female WISTAR Crl: WI(Han) rats was treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was suspended with the vehicle aqua ad injectionem (sterile water) at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.

Two further groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 300 mg/kg body weight. The test item was suspended with the vehicle aqua ad injectionem (sterile water) at a concentration of 0.03 g/mL and administered at a dose volume of 10 mL/kg.

All animals used in the study after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15.All animals were necropsied and examined macroscopically.

Results per Step

Step Sex / No. Starting Dose (mg/kg bw) Number of Animals Number of Intercurrent Deaths
1 Female / 1 - 3 2000 3 3
2 Female / 4 - 6 300 3 0
3 Female / 7 - 9 300 3 0

bw = body weight

All animals treated with the test item at a dose of 2000 mg/kg were found dead on test day 1. All remaining animals survived until the end of the study without showing any signs of toxicity.

The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, prone position, hunched posture, piloerection and half eyelid-closure.

Throughout the 14-day observation period, the weight gain of the surviving animals was within the normal range of variation for this strain.

Macroscopic findings of surviving animals:

At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

Macroscopic findings of animals not having survived until the end of the observation period:

Necropsy revealed blood in parts of the gastrointestinal tract.

 

LD50:                                      500mg/kg bw

Species/strain:                     WISTAR Crl: WI(Han) rats

Vehicle:                                  Aqua ad injectionem (sterile water)

Number of animals:            3 per step / 3 steps performed

Method:          OECD 423, EC 440/2008, Method B.1 tris, OPPTS 870.1100

Conclusion

Under the conditions of the present study, a single oral application of the test item Naphthalenesulfonic acid, bis(1-methylethyl)-, methyl derivs., sodium salt to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity and mortality.

Under the conditions of the present study, a single oral application of the test item Naphthalenesulfonic acid, bis(1-methylethyl)-, methyl derivs., sodium salt to rats at a dose of 300 mg/kg body weight was associated with no signs of toxicity or mortality.

The median lethal dose of Naphthalenesulfonic acid, bis(1-methylethyl)-, methyl derivs., sodium salt after a single oral administration to female rats, observed over a period of 14 days is:

LD50cut-off (rat):500mg/ kg bw

According to Annex I of Regulation (EC) 1272/2008 the test item Naphthalenesulfonic acid, bis(1-methylethyl)-, methyl derivs., sodium salt has obligatory labelling requirement for toxicity and is classified into Category 4.

According to GHS (Globally Harmonized Classification System) the test item Naphthalenesulfonic acid, bis(1-methylethyl)-, methyl derivs., sodium salt has obligatory labelling requirement for toxicity and is classified into Category 4.