Sebacic acid, compound with hexane-1,6-diamine (1:1)

Endpoint summary

Description of key information

LD50 oral: 4900 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Short observation period; limited documentation; however, basic data are given.

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

The test substance was administered via single dose gavage to groups of one or five animals per dose level. Animals were observed approximately 1-3 hours after dosing and then daily over a period of 8 days. At necropsy, all rats were examined for gross pathological changes.

GLP compliance:

no

Remarks:

pre-GLP study

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder
- Fasting period before study: yes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12h/12h

Route of administration:

oral: unspecified

Vehicle:

not specified

Doses:

500, 1000, 2000, 4000, 5000, 8000, 10000 mg/kg bw

No. of animals per sex per dose:

1 or 5 animals per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 8 days
- Frequency of observations: approximately 1-3 hours after dosing and then daily over a period of 8 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross pathology

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

ca. 4 900 mg/kg bw

Based on:

test mat.

Mortality:

All but one of the animals given 5000 mg/kg bw and more died; late deaths were observed. See table 7.2.1/1.

Clinical signs:

other: Lethal doses caused seizures. Sublethal doses led to stiff gait, apathy, reduced appetite, diarrhoea, and rough coat.

Gross pathology:

At necropsy, signs of gastro-intestinal tract irritation and intestinal bleeding were found.

Table 7.2.1/1: mortality data

Dose [mg/kg]	Mortality rate	Death occurred within
10000	1/1	3  hours
8000	5/5	1-2 days
5000	4/5	1-8 days
4000	0/5
2000	0/1
1000	0/1
500	0/1

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the test item is not classified for acute oral toxicity in rats as LD50 is higher than 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study (BASF, 1956), groups of 1 to 5 rats were given a single dose of Hexamethylenediamine adipate, dry (purity not given) at doses of 500, 1000, 2000, 4000, 5000, 8000, and 100000 mg/kg bw and were observed for 8 days. Necropsy was performed at the end of the study.

All but one of the animals given 5000 mg/kg bw and more died; late deaths were observed. Lethal doses caused seizures. Sub-lethal doses led to stiff gait, apathy, reduced appetite, diarrhea, and rough coat. At necropsy, signs of gastro-intestinal tract irritation and intestinal bleeding were found.

Based on this study,the oral LD50 in rats was approximately 4900 mg/kg bw.

 

Under the test conditions, the test substance is not classified for acute oral toxicity according to the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC criteria, as for sebacic acid, compound with hexane-1,6 -diamine (1:1), considering the read-accross approach.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 900 mg/kg bw

Quality of whole database:

Good quality study according to a standardised guideline (pre-GLP study).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

READ-ACROSS JUSTIFICATION

When toxicological data required by REACH regulation are missing for sebacic acid, compound with hexane-1,6-diamine (1:1), read-across approach with adipic acid, compound with hexane-1,6-diamine (1:1) (CAS RN: 3323-53-3) is performed. This approach is justified by the information below:

1) Structural similarity

Both substances are acid compounds with hexane-1,6-diamine and therefore these acids have similar chemical structure.

As the difference between the 2 molecules is acids, the comparison is done between sebacic acid and adipic acid.

Both are linear diacids with structural formula of COOH-(CH2)₄-COOH for adipic acid and COOH-(CH2)₈-COOH for sebacic acid.

 

2) Similar physico-chemical properties

Below are the physic-chemical properties of both acids:

	Sebacic acid	Adipic acid
Melting point	135°C (exp)	150.85°C (exp)
Boiling point	> 420°C ; decomposes before boiling (exp)	337.5°C (published data)
Water solubility	224 mg/L at 25°C	23 g/L at 25°C
Vapour pressure	9x10E-6 Pa at 25°C	9.7 Pa at 18.5°C
Log kow	1.5 at 23°C and pH=3	0.093 at 25°C and pH=3.3
Flammability	Not flammable	Not flammable
Explosivity	Not explosive	Not explosive
Oxidizing properties	Not considered as oxidizing (SAR)	Not considered as oxidizing (SAR)

 

3) Similar toxicity potential

Both acid are:

- Not classified by oral route

- Not classified by dermal route

- Not classified for skin irritation

- Sebacic acid is slightly irritating to eyes and adipic acid causes serious eye damage

- Not classified for skin sensitization

 

To conclude, based on the similar chemical structure, physico-chemical properties and toxicity potential of diacids, the toxicity data obtained on adipic acid, compound with hexane-1,6-diamine (1:1) can be used to assess the toxicological profile of sebacic acid, compound with hexane-1,6-diamine (1:1). Data on adipic acid, compound with hexane-1,6-diamine (1:1) are used in a read-across approach in this dossier.

Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for classification or non-classification

Based on oral LD50 of 4900 mg/kg of the analog adipic acid, compound with hexane-1,6 -diamine, no classification is required for sebacic acid, compound with hexane-1,6 -diamine according to the directive 67/548/EC and the CLP 1272/2008 regulation criteria.