Reaction mass of morpholine and 6-[(p-tosyl)amino]hexanoic acid, compound with morpholine (1:1)

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

other: An assessment was undertaken based on available data on the individual constituents of the substance

Adequacy of study:

key study

Study period:

2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: An assessment was undertaken based on available data on the individual constituents of the substance

Data source

Reference

Reference Type:

other: expert assessment

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

An assessment was undertaken based on available data on the individual constituents of the substance.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

morpholin-4-ium morpholine 6-(4-methylbenzenesulfonamido)hexanoate

EC Number:

944-090-8

Molecular formula:

C13H19NO4S.C4H9NO/C4H9NO/H2O

IUPAC Name:

morpholin-4-ium morpholine 6-(4-methylbenzenesulfonamido)hexanoate

Test material form:

liquid

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

1

Key result

Dose descriptor:

NOAEL

Remarks:

maternal toxicity

Effect level:

75 mg/kg bw/day (nominal)

Based on:

other: maternal toxicity induced by one of the constituents of the substance

Sex:

female

Basis for effect level:

food consumption and compound intake

haematology

organ weights and organ / body weight ratios

Remarks on result:

other: An assessment was undertaken based on available data on the individual constituents of the substance

2

Dose descriptor:

NOAEL

Remarks:

fertility

Effect level:

1 600 mg/kg bw/day (nominal)

Based on:

other: No effects on fertility were observed for the constituents of the substance at up to 1,600 mg/kg bw/d

Sex:

male/female

Remarks on result:

other: An assessment was undertaken based on available data on the individual constituents of the substance

Target system / organ toxicity (P0)

Key result

Critical effects observed:

no

Results: F1 generation

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Remarks:

developmental toxicity

Generation:

F1

Effect level:

400 mg/kg bw/day (nominal)

Based on:

other: suspected developmental toxicity induced by one of the constituents of the substance at 1,600 mg/kg bw/d

Sex:

male/female

Basis for effect level:

mortality

Remarks on result:

other: An assessment was undertaken based on available data on the individual constituents of the substance

Target system / organ toxicity (F1)

Key result

Critical effects observed:

no

Overall reproductive toxicity

Key result

Reproductive effects observed:

not specified

Any other information on results incl. tables

See attached document

Applicant's summary and conclusion

Conclusions:

An assessment of the toxicity to reproduction of the registered substance was undertaken based on available data on its individual constituents. None of these constituents meet the criteria for classification as toxic to reproduction according to Regulation (EC) N° 1272/2008. It is therefore considered that Reaction mass of morpholine and 6-[(p-tosyl)amino]hexanoic acid, compound with morpholine (1:1) does not meet the criteria for classification as toxic to reproduction.

Executive summary:

The toxicity to reproduction of Reaction mass of morpholine and 6-[(p-tosyl)amino]hexanoic acid, compound with morpholine (1:1) via the oral route is expected to be driven by the toxicity to reproduction of its constituents – 6-[[(4-methylphenyl)sulphonyl]amino]hexanoic acid, morpholine, and water.

Reliable data on 6-[[(4-methylphenyl)sulphonyl]amino]hexanoic acid was used to derive a NOAEL_(fertility) = 1,600 mg/kg bw/day, a NOAEL_{(maternal toxicity)} = 400 mg/kg bw/day and a NOAEL_{(developmental toxicity)} = 400 mg/kg bw/day.

It was not possible to identify in the literature any studies investigating the effects of morpholine to fertility or reproductive organs following exposure via the oral route. Repeated-dose toxicity studies performed on morpholine via inhalation and investigating the effects of the substance to reproductive organs did not report any effects. The available information on morpholine allowed to derive a NOAEL_{(maternal toxicity)} = 75 mg/kg bw/day and a NOAEL_{(developmental toxicity)} = 750 mg/kg bw/day for the oral route.

Water is included in Annex IV of REACH and is not considered as toxic to reproduction.

None of the constituents of Reaction mass of morpholine and 6-[(p-tosyl)amino]hexanoic acid, compound with morpholine (1:1) is classified as toxic to reproduction therefore the substance is not considered as toxic to reproduction.

It is considered a conservative approach to apply to the substance the lowest NOAEL derived for its individual constituents, therefore with a NOAEL_(fertility) = 1,600 mg/kg bw/day, NOAEL_{(maternal toxicity)} = 75 mg/kg bw/day, and NOAEL_{(developmental toxicity)} = 400 mg/kg bw/day of Reaction mass of morpholine and 6-[(p-tosyl)amino]hexanoic acid, compound with morpholine (1:1).