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

Endpoint summary

Description of key information

SKIN IRRITATION
In a primary dermal irritation study (BASF 1956) two rabbits (strain and sex unknown) were dermally exposed to a 50% aqueous solution of AH salt (limit of solubility) for up to 15 minutes under semiocclusive conditions. This treatment did not cause any sign of irritation in both rabbits.
In a second study used as weight of evidence (Monsanto 1978) the skin of 6 rabbits was exposed to Nylon 6,6 salt solution for 24 hours. An erythema score of 1 was observed after 24 hours which was reversible within 72 hours.

EYE IRRITATION
In a primary eye irritation study (BASF 1956), a 50% aqueous preparation of AH salt (limit of solubility) was instilled without rinsing into one eye of each of 2 rabbits (strain and sex not given). The eyes of 2 rabbits were examined 10 minutes, and 1, 3, and 24 hours after instillation of an 50% aqueous solution of the test substance into the right eye. The other eye served as control and were treated with physiological saline. The test material caused slight and transient conjunctivitis in two rabbits after exposure up to 3 hours. All effects were completely reversible within 24 hours.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

Before OECD Guideline 404 was established in 1982, skin irritation was tested using an internal method (BASF test). White Vienna rabbits were used. 2 animals were treated for 1, 5 and 15 minutes and 2 other animals for 20 hours using occlusive conditions. An application site of 2.5 x 2.5 cm was covered with the liquid test substance on a patch. After the application time of 1, 5, and 15 minutes, respectively, the skin was first washed with undiluted Lutrol 9, then with an aqueous Lutrol solution (50 %). The skin of the animals that had been treated with the test substance for 20 hours, remained unwashed.
The short exposure time of 15 minutes is thought not to impair the evaluation of the skin irritation potential significantly. As a 50% aqueous preparation is the limit of solubility, no higher concentrations would have been achieved if neat AH salt had been tested and this deviation from the test guideline is thought not to impair the evaluation of the skin irritation potential significantly.

GLP compliance:

no

Remarks:

pre-GLP study

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

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

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 50%; saturated solution; pH = 7.5

Duration of treatment / exposure:

1, 5 and 15 minutes

Observation period:

No data

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: back, an application site of 2.5 X 2.5 cm was covered with the liquid (37°C; approx. 1 ml)

REMOVAL OF TEST SUBSTANCE
- Washing: yes, the sites were wiped with a mixture of acetic acid and polyethylene glycol (Lutrol) after the end of the exposure period.

SCORING
Descriptive scores of the raw data have been converted to Draize numerical scores.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

n = 2

Time point:

other: unspecified

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

short-time test with 1; 5; 15 min exposure

Irritation parameter:

edema score

Basis:

mean

Remarks:

n = 2

Time point:

other: unspecified

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

short-time test with 1; 5; 15 min exposure

Irritant / corrosive response data:

None of two animals showed any effects of irritation at any application site.
primary dermal irritation index (PDII), mean of n=2: Score = 0

Limited documentation; no further details.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not irritating to the skin according to EU GHS classification and according to annex VI-Directive 67/548/EEC.

Executive summary:

Application of a saturated aqueous solution of the test substance (concentration ca. 50%) to the back of two rabbits for up to 15 minutes did not produce any signs of irritation.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

more animals, observation time up to 168 hours

Principles of method if other than guideline:

according A.T.S. 8/73

GLP compliance:

no

Remarks:

pre GLP-study

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not required

Amount / concentration applied:

0.5 ml of undiluted substance

Duration of treatment / exposure:

Exposure 24 hours

Observation period:

4, 24, 48, 72, 168 hours

Number of animals:

6 rabbits

Details on study design:

6 NewZealand Albino Rabbits were tested with 0.5 ml undiluted substance. Erythema and edema were scored, the max. score =8

Irritation parameter:

erythema score

Basis:

mean

Remarks:

n = 6

Time point:

other: 24 - 72 h

Score:

0.3

Max. score:

8

Reversibility:

fully reversible

Remarks:

72 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

n = 6

Time point:

other: 24 - 72 hours

Score:

0

Max. score:

8

Remarks on result:

no indication of irritation

Other effects:

No data

 

Primary skinirritation = not classified as primary skin irritant

 

Hours	4	4	24	24	48	48	72	72	168	168
Animal number	Erythema I       A	Edema I      A	Erythema I       A	Edema I      A	Erythema I       A	Edema I      A	Erythema I       A	Edema I       A	Erythema I       A	Edema I      A
1	o     o	0     o	0      o	0     o	0      o	0     o	0      o	0      o	0      o	0     o
2	0      o	0     o	1      1	0     o	0      o	0     o	0      o	0      o	0      o	0     o
3	0      o	0     o	1      1	0     o	1      1	0     o	0      o	0      o	0      o	0     o
4	0      o	0     o	1      1	0     o	0      1	0     o	0      o	0      o	0      o	0     o
5	0      o	0     o	1      1	0    o	0       1	0     o	0      o	0      o	0      o	0     o
6	0      o	0     o	0      1	0     o	0      o	0     o	0      o	0      o	0      o	0     o
Mean score	0.0		0.7		0.3		0.0		0.0

 

 

 

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not irritating to the skin according to EU GHS classification and according to annex VI-Directive 67/548/EEC.

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

limited documentation, 50 µl instead of 100 µl test substance instilled

Principles of method if other than guideline:

Data on purity are lacking, but as there was no strong irritation observed, this is thought not to impair the evaluation of the eye irritation potential significantly. As a 50% aqueous preparation is the limit of solubility, no higher concentrations would have been achieved if neat AH salt had been tested and this deviation from the test guideline is thought not to impair the evaluation of the eye irritation potential significantly

GLP compliance:

no

Remarks:

pre-GLP study

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Breeder
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

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

Vehicle:

water

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 50%

Duration of treatment / exposure:

instillation once without rinsing

Observation period (in vivo):

10 minutes, and 1, 3 and 24 hours

Number of animals or in vitro replicates:

2

Details on study design:

REMOVAL OF TEST SUBSTANCE
- The eye was left unwashed.
SCORING SYSTEM:
- Descriptive scores of the raw data have been converted to Draize numerical scores.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

n = 2

Time point:

24 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

n = 2

Time point:

24 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

n = 2

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

other: after 10 min and 1 to 3 hours mean score of 1

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

n = 2

Time point:

24 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Until 3 hours after administration of the test substance, very slight (equivalent to Draize score 0) and transient conjunctivitis was observed in both tested animals. All effects were completely reversible at 24 hours after instillation (no effects were observed in the control eyes treated with physiological saline).

Other effects:

No data

Limited documentation; no further details.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is not irritating to eyes according to EU GHS classification and according to annex VI-Directive 67/548/EEC.

Executive summary:

A saturated (ca. 50%) aqueous solution of the test substance as instilled into one eye of each of two rabbits. For control purpose, physiological saline was instilled into the other eye. Until 3 hours after administration of the test substance, very slight and transient conjunctivitis was observed in both tested animals. All effects were completely reversible at 24 hours after instillation. No effects were observed in the control eyes treated with physiological saline. 

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation

The short exposure time of 15 minutes is thought not to impair the evaluation of the skin irritation potential significantly. As a 50% aqueous preparation is the limit of solubility, no higher concentrations would have been achieved if neat AH salt had been tested and this deviation from the test guideline is thought not to impair the evaluation of the skin irritation potential significantly. Data on purity are lacking, but as there was no irritation observed, this is thought not to impair the evaluation of the eye irritation potential significantly.

Due to the short exposure time in the first study (BASF AG 1956), a second study (Monsanto 1978) was used as weight of evidence.

In this study the skin of 6 rabbits was exposed to 0.5 mL Nylon 6,6 salt solution for 24 hours. An erythema score of 1 was observed after 24 hours which was reversible within 72 hours. Data on purity are not available.

Conclusion: A 50 % aqueous preparation of AH salt as well as Nylon salt 6,6 salt solution was not irritating to the skin of rabbits.

Eye Irritation

Data on purity are lacking, but as there was no strong irritation observed, this is thought not to impair the evaluation of the eye irritation potential significantly. As a 50% aqueous preparation is the limit of solubility, no higher concentrations would have been achieved if neat AH salt had been tested and this deviation from the test guideline is thought not to impair the evaluation of the eye irritation potential significantly.

Indeed, a very slight and transient conjunctivitis was observed within the first 3 hours in both test animals. However, in more ancient studies conducted by BASF Akteingesellschaft, the term "very slight" was used equivalent to Draize score 1. All eyes were normal at the 24 -hour reading. Therefore no readings were necessary to be done at 48 and 72 hours as required by the guideline. As there were only very slight reactions after 3 hours and as no signs of irritation were observed after 24 hours, the test substance can be assumed to have no eye irritating properties.

Conclusion: A 50% aqueous preparation of AH salt was slightly irritating to the eyes of rabbits.

Justification for classification or non-classification

There is no need to classify AH-Salt for skin or eye irritation according to the Directive 67/548/EC and according to EU GHS criteria (Regulation (EC) N° 1907/2006)..