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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.