4-(cyclohexylamino)butane-1-sulfonic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to conditions described in Column 2 of Section 8.5.3 of Annex VIII testing by the dermal route is appropriate if: (1) inhalation of the substance is unlikely; and (2) skin contact in production and/or use is likely; and (3) the physicochemical and toxicological properties suggest potential for a significant rate of absorption through the skin. Since 4-(cyclohexylamino)butane-1-sulfonic acid is only imported as part of polymers in Europe exposure to substantial concentrations of monomeric 4-(cyclohexylamino)butane-1-sulfonic acid is very unlikely. Even so since 4-(cyclohexylamino)butane-1-sulfonic acid has a high hydrophilicity (Log Pow = -2) and a high water solubility (475 g/L) its ability to cross the stratum corneum is unlikely[1]. Also as 4-(cyclohexylamino)butane-1-sulfonic acid has a low acute oral toxicity combined with a low dermal absorption it is unlikely that the acute dermal toxicity will exceed the oral toxicity. Since criteria (2) and (3) in Column 2 of section 8.5.3 of Annex VIII are not fulfilled, testing by the dermal route for 4-(cyclohexylamino)butane-1-sulfonic acid is considered not appropriate and thus testing is waived.

See Cross references for relevant supporting data on uses, toxicological data and physical and chemical properties.

[1] Guidance for the implementation of REACH. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European Chemical Agency, Version 3.0 November 2017

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Justification for no uses reported:

other: This is a registration according to REACH Article 6(3). The substance is imported as part of polymers only and therefore identified uses are not applicable (in accordance with REACH Article 2(9)).

Justification for no exposure assessment:

substance does not meet the criteria for classification as hazardous, nor is assessed to be a PBT or vPvB, as per REACH Article 14(4) during its entire life cycle

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

In an acute oral toxicity study with the substance performed in accordance with OECD 423, an LD50 of >2000 mg/kg bw was determined. As no mortality occurred, the LD50 cut-off value was considered to be 5000 mg/kg body weight according to the OECD 423 test guideline.

Based on the expert statement and as the criteria in Column 2 of Section 8.5.2 of REACH are not fulfilled testing by the inhalation route is not performed.

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Endpoint conclusion:

no study available

Endpoint conclusion:

no study available

Oral

The acute oral toxicity of the substance was determined in accordance with OECD 423 (2001) and according to GLP principles. The substance was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight. No mortality occurred. Hunched posture and/or piloerection were noted for all animals between Days 1 and 6. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The acute oral toxicity (LD50) was determined to be > 2000 mg/kg bw. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 5000 mg/kg body weight. 

Based on the results of the acute oral toxicity study, the substance does not need to be classified for acute oral toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

The water solubility of 4-(cyclohexylamino)butane-1-sulfonic acid at 20°C is 475 g/L using the flask method.

Water solubility:

475 g/L

at the temperature of:

20 °C

The water solubility of 4-(cyclohexylamino)butane-1-sulfonic acid was determined in a test performed according to OECD guideline 105 and GLP principles, using the flask method. 10.0 g of the substance was weighed into glass vessels to which 10 mL double distilled water was added. The vessels were stirred for 24, 48 and 72 hours, after which the water phases were filtered. Liquid chromatography was used for qualitative assessment from samples taken at 24 h, 48 h and 72 h. The results showed a water solubility of 556, 467 and 483 g/L at 24 h, 48 h and 72 h samples, respectively. The the water solubility of the test item was given as the mean value of the 48- and 72-hour measurements. Based on the flask method test, the water solubility of 4-(cyclohexylamino)butane-1-sulfonic acid, at 20°C was 475 g/L.

Cross-reference 4

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

The n-octanol - water partition coefficient of the substance at 20°C and at pH 7 and pH 13 was determined to be 0.011 (log Pow = -2.0) using the shake flask method (OECD 107).

Log Kow (Log Pow):

-2

at the temperature of:

20 °C

The n-octanol - water partition coefficient of 4-(cyclohexylamino)butane-1-sulfonic acid was determined according to OECD guideline 107 and GLP principles using the flask method. Based on the Rekker calculation method, the Pow was determined to be 2.8 (log Pow 0.5). The Perrin calculation method was used to calculate pKa values in the logarithm range of 1 -14 for basic molecular groups of the test item (pKa of 11.2). Based on these calculations, the flask method was used for the determination of Pow and log Pow at both pH 7 and pH 13. A validated analytical method was used (UPLC-MS/MS) for quantitative analysis. Results showed a Pow of 0.011 (log Pow -2.0) at 20°C and both pH 7 and pH 13.

Data source

Reference

Reference Type:

other: Expert statement

Title:

Unnamed

Year:

2020