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Administrative data

Description of key information

Acute toxicity data show that LAS IPA is not toxic after oral or dermal administration. Details can be found below in the discussion section.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
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 Laboratoties UK Ltd.
- Age at study initiation: 8 -12 weeks
- Housing: up to 4 animals/group, suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

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

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no vehicle used
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

In the absence of toxicity data of the test material a dose of 300 mg/kg bw was applied initially to one animal. Since no mortality was observed 1 more animal was used to test the higher dose of 2000 mg/kg bw. No mortality was detected; four aditional animals were treated with a single gavage dose of 2000 mg/kg bw.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
One animal tested at 300 mg/kg bw, five animals treated with 2000 mg/kg bw.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2 and 4 h post-treatment and daily for 14 days. Morbity/mortality checks twice per day. Weighing on Day 0, Day 7 and Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy.
Statistics:
not required
Preliminary study:
No toxic effects were seen in the sighting study at 300 mg/kg bw.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks:
97% LAS IPA
Mortality:
No mortality observed
Clinical signs:
No signs of toxicity
Body weight:
No significant changes seen in body weights
Gross pathology:
No abnormalities detected
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this test, benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with 2-propanamine has an oral LD50 higher than 2000 mg/kg bw.

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  benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with 2-propanamine (1:1) (97%) at doses of   300 or 2000  mg/kg bw. No effects on the animals were seen at both dose levels, and therefore, the main study was performed with the higher dose of 2000 mg/kg bw, as a solution in arachis oil BP.

 

 Oral LD50females> 2000 mg/kg bw

No adverse effects were detected.   

Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with 2-propanamine (1:1) is of low toxicity based on an LD50 higher than the classification criterion. The substance shall not be labelled for acute oral toxicity.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The oral LD50 of LAS IPA is higher than 2000 mg/kg bw. The whole database is sufficient to fully address this endpoint.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
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 2-propanamine, and therefore the requirement for acute inhalation toxicity is waived.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The calculated oral LD50 of LAS IPA (molar basis) is >2000 mg/kg bw. The whole database is sufficient to fully address this endpoint.

Additional information

Oral toxicity

LAS IPA

In an acute oral toxicity study (fixed dose) fasted young adult female Wistar rats (one per dose) were given a single oral dose of  benzenesulfonic acid, 4-C10-13-sec-alkyl derivs.-, compd. with 2-propanamine (97%) at doses of 300 or 2000  mg/kg bw. No effects on the animals were seen at both dose levels, and therefore, the main study was performed with the higher dose of 2000 mg/kg bw. No adverse effects were seen and the LD50 is higher than 2000 mg/kg bw.

Additional information

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.

IPA

Based on data from a single publication (Myers & Ballantyne, 1997), the oral LD50 of IPA is <173 mg/kg bw), when tested in Wistar rats orally by gavage. The animals suffered from lung hemorrhage, kidney and adrenal congestion, gastric and intestinal hemorrhage, and ulceration. Most surviving animals did not show any significant gross pathological signs.

Compared to the LD50 for LAS-IPA (> 2000 mg/kg bw), this LD50 is much lower. This substantial difference between the two LD50s can be explained by the reactive nature of the alkyl amine (IPA), due to its strong basicity, as well as ability to engage in e.g. Maillard reactions. Adverse effects observed after a single oral administration of IPA are primarily attributable to the alkyl amine itself and not to the ammonium cation (IPA+).

The normalized LD50 of IPA to LAS-IPA is <1130 mg/kg bw. Nonetheless, since no exact values are available for both LAS-IPA and IPA making a comparison is difficult. To a certain extent differences in LD50s can be also explained by the variability in toxicity testing.

It is therefore considered appropriate to base the acute oral toxicity endpoint and classification decision on the LD50 derived in the recent study performed with the substance LAS-IPA itself.

Dermal toxicity

The endpoint of acute dermal toxicity was addressed with data on LAS Na and IPA, since there is no available information on LAS-IPA.

IPA

The result of the study used with isopropylamine, shows a dermal LD50 higher than 400 mg/kg bw. No further doses were tested. With lack of further information, this would put the substance on a classification category of Acute Tox.3, H311.

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
GLP, Guideline study performed with the substance itself. All other information come from studies performed with LAS Na and IPA, which are considered less relevant.

Justification for selection of acute toxicity – dermal endpoint
The weight of evidence approach was applied to address the endpoint of acute dermal toxicity, since no study available can per se address this requirement; information from two available studies were used.

Justification for classification or non-classification

Based on the results of the key test the oral LD50 for LAS IPA is higher than 2000 mg/kg bw, which does not lead to any classification for acute oral toxicity (EC Regulation 1272/2008).

The endpoint of acute dermal toxicity was addressed with data from LAS Na and IPA. The dermal LD50 for LAS Na is >2000 mg/kg bw. The dermal LD50 for IPA is higher than 400 mg/kg bw, i.e. 2600 mg/kg bw for LAS IPA, calculated by scaling based on the molecular weight.LAS IPA shall not be classified for acute dermal toxicity.