Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs., compds. with isopropanolamine

Endpoint summary

Description of key information

Acute toxicity data indicate low toxicity of LAS MIPA after administration via the oral route and no toxicity via the dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 September to 09 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd.
- Age at study initiation: 8-12 weeks
- Weight at study initiation:
- Fasting period before study: yes
- Housing: in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum
- Water: d libitum
- Acclimation period: at least 5 days

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

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL (dose 300 mg/kg bw preliminary test), 200 mg/ml (dose 200 mg/kg bw), 300 mg/ml (dose 300 mg/kg bw main study)
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: the product did not dissolve/suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 300 mg/ml

Doses:

sighting study: product doses 300 and 2000 mg/kg bw; active substance doses 234 and 1560 mg/kg bw
main study: product dose 300 mg/kg bw, active substance dose 234 mg/kg bw

No. of animals per sex per dose:

4 + 1 (main study), 1 (preliminary study)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were performed 0.5, 1, 2, and 4 h after dosing and thereafter daily for up to 14 days. Weighing was performed on Day 0, Day 7 and Day 14 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

Not used

Preliminary study:

The animal treated with the highest dose (2000 mg/kg bw) was found dead 4 h post-treatment. At this dose level ataxia, hunched posture, lethargy and ptosis were observed, while at the necropsy the findings reveal dark liver and kidneys, liquid and gas accumulated in the stomach and haemorrhagic gastric mucosa. The main study was continued with the dose of 300 mg/kg bw.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 234 - < 1 560 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality.

Clinical signs:

other: Hunched posture in all animals, ataxia in one animal during the first day. The signs disappeared one day post-treatment.

Gross pathology:

No abnormalities detected.

Other findings:

No other findings.

Interpretation of results:

sligthly toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1)is of slight toxicitybased on the LD50range infemales. The substance shall be labelled as Acute Tox. 3.

Executive summary:

In the preliminary phase of an acute oral toxicity study (fixed dose) fasted young adult female Wistar rats (one per dose)were given a single oral dose of MARLON AMI 80 (78% benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1) in 22% 1,2-propylene glycol)at doses of   300 or 2000  mg/kg bw (product dose). The animal treated with the highest dose was found dead and therefore the main study was performed with the lower dose of 300 mg/kg bw (active substance: 234 mg/kg bw).

234 mg/kg bw>Oral LD50 females mg/kg bw < 1560 mg/kg bw

Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1)is of slight toxicity based on the LD50 range in females. The substance shall be labelled as Acute Tox. 3.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

GLP, Guideline study; 234 mg/kg bw>Oral LD50 LAS MIPA females mg/kg bw < 1560 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Oral toxicity

LAS MIPA

In an acute oral toxicity study (fixed dose) with female Wistar rats the LD50 of  MARLON AMI 80 (78% benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1) in 22% 1,2-propylene glycol) the LD50 was between 300 and 2000 mg/kg bw, i.e. for benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1): 234 mg/kg bw>Oral LD50 females mg/kg bw < 1560 mg/kg bw.

Supporting information

MIPA

In an acute oral toxicity study, comparable to OECD TG 401, US-rats (5/sex/dose) were administered MIPA at 194-6208 mg/kg bw by single dose (gavage) followed by a 14-days observation period (BASF AG, 1965). Clinical signs included restlessness, stagger, creep, slight abdominal position, anemia, mouth discharge, compulsive chewing, dyspnoea, apathy, tonic-clonic convulsions, and overnight exitus. Surviving animals recovered slowly and showed apathy, dyspnoea, partly slight stagger and decelerated motion. Findings at necropsy included red discoloration of abdominal viscus (6208 mg/kg bw dose group), reddish livid discoloration of the abdominal viscus (at 3104 mg/kg bw), bowel irritation and dilation of the stomach (at 2425 mg/kg bw), bronchitis, and bronchiectasia. The LD50 was 2813 mg/kg bw.

LAS Na

A study comparable to OECD guideline 401 found an acute oral LD50 of 1080 mg/kg. According to EU GHS guidelines, the test substance is a Category IV toxicant.

The supporting studies examined the oral toxicity for various concentrations of the test substance (75%, 65% and 60%) in rats. The studies followed the same test protocol and methods as the key study. The effects and symptoms observed with the key study for the test substance were also observed in the supporting study. The acute oral LD50’s determined for the concentrations were 1600 mg/kg, 2190 mg/kg and 2760 mg/kg for 75%, 65% and 60% actives, respectively. According to CLP-Regulation, the test substance is a Category IV toxicant (H302: Harmful if swallowed) at concentrations equal to or greater than 65%, while it is not classified at lower concentrations.

Dermal toxicity

MIPA:

In an acute percutaneous absorption test in rabbits, MIPA was applied at doses of 630 - 5000 mg/kg bw (Carreon and Yakel, 1981; study is only available as a secondary source and is requested). Marked redness, moderate swelling, and marked necrosis of the skin were observed. At all doses, rabbits were lethargic. At doses of 630 and 1300 mg/kg bw, anorexia was observed, and at a dose of 1300 mg/kg bw, diarrhea was observed. At necropsy at the end of a 2-week observation period, no treatment-related changes were noted. The LD50 was 1851 mg/kg bw.

LAS Na:

The clipped skin on the backs of five male and five female rats were exposed to LAS Na under an occlusive dressing for 24 hours and observed for another 14 days. Results indicate slight erythema and slight oedema but no acute mortality. The dermal LD50 is > 2000 mg/kg.

Justification for selection of acute toxicity – oral endpoint

Only one study available with LAS MIPA

Justification for selection of acute toxicity – inhalation endpoint

According to REACH Regulation substances other than gases shall be tested through one more route except for the oral for acute toxicity (inhalation or demal). The dermal route was considered more appropriate for Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with isopropanolamine (1:1), and therefore the requirement for acute inhalation toxicity is waived.

Justification for selection of acute toxicity – dermal endpoint

Data available for LAS Na and MIPA. Weight of evidence approach applied.

Justification for classification or non-classification

Based on the results of the test the oral LD50 for LAS MIPA is between 234 and 1560 mg/kg bw, which leads to a classification of Acute Tox. 3 or 4 (EC Regulation 1272/2008). Since no deaths were recorded at the dose level of 234 mg/kg bw and considering the supporting information from LAS Na and MIPA, it is safe to assume that the oral LD50 for MIPA is not lower than 300 mg/kg bw. Therefore, the substance shall be labelled as Acute Tox. 4.

The endpoint of acute dermal toxicity was addressed based on data from LAS Na and MIPA. The dermal LD50 for LAS Na is higher than 2000 mg/kg bw. The dermal LD50 for MIPA is 1851 mg/kg bw, i.e. 9921 mg/kg bw for LAS MIPA, calculated by scaling based on the molecular weight. LAS MIPA shall not be classified for acute dermal toxicity.