N,N,N',N'-tetrakis(2-hydroxypropyl)adipamide

Endpoint summary

Description of key information

Skin irritation: Negative.
Eye irritation: Negative.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from April 17, 1996 to April 25, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline test with GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Test System Rationale: New Zealand White Rabbit - Chbb:NZW(SPF)
Source: Recognized by the International guidelines as the recomended test system (e.g. EPA, OECD, EEC)
Number of animals per test: 1 male, 2 females
Age at treatment: 15 weeks
Body weight at start of acclimatization: male: 2.8 kg, females: 2.2 - 3.0 kg
Body weight at start of treatment: male: 3.1 kg; females: 2.4 - 3.1 kg
Identification: By unique cage number and corresponding ear tags.
Acclimatization: Four days under test conditions after examination. Only healthy animals were used study.
Allocation: male no. 13; female nos. 14 - 15
Conditions
Standard Laboratory Conditions.
Air-conditioned with 10 - 15 air changes per hour and continuously monitored environment with target ranges for temperature of 20 ±3 °C and for relative humidity between 40 - 70% (values above 70% during cleaning process possibly), 12 hours artificial fluorescent 12 light/12 hours dark, music during the light period.
Accommodation: Individually in stainless steel cages with an automatic equipped with feed hoppers, drinking water bowls and wood for gnawing.
Diet: Pelleted standard Kliba 341 rabbit maintenance diet (batch 93/96) ad libitum from Kliba Muhlen AG, CH-4303 Kaiseraugst), Results of analysis for contaminants are included in this report.
Water: Community tap water from Itingen, ad libitum. Results of bacteriological, chemical and contaminant analyses are included in this report.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

bi-distilled water

Controls:

other:

Amount / concentration applied:

0.5 g of the test article was applied to approx. 6 cm² of the intact skin of the clipped area

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hrs after administration

Number of animals:

1 males, 2 females

Details on study design:

Approximately 24 hours before treatment, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 100 square centimeters (10 cm x 10 cm).
The skin of the animals was examined once, 1 day prior to test article administration.
Only those animals with no signs of skin injury or irritation were used in the test.
On the day of treatment, 0.5 g of the test article was applied to approx. 6 cm² of the intact skin of the clipped area. It was covered with a 2.5 cm x 2.5 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. The test article was applied in such a position as to preclude oral ingestion after removal of the dressing.
The duration of treatment was 4 hours.Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
The skin reaction was assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test article.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

The dermal irritation scores were evaluated in conjunction with the nature and reversibility or otherwise of the responses observed. The individual scores do not represent an absolute standard for and they are viewed as reference values, a severe test and the results are not conditions.
irritation
PRIMID QM 1260 showed a primary irritation score of 0.11 when applied to healthy intact rabbit skin.
Local signs (mean values from 24 to 72 hours) consisted of grade 0,11 erythema and grade 0.00 edema. Erythema was noted in one animal only and was reversible after 48 hours.

CORROSION
No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Other effects:

Necropsy
No necropsy was performed in the animals euthanized at termination of observation.
VIABILITY / MORTALITY AND CLINICAL SIGNS
No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.
COLORATION
No staining by the test article of the treated skin was observed.
BODY WEIGHTS
The body weight gain of all rabbits was within the normal range of variability.

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

No test-related response was observed in the study and thus, the test substance is a non-irritant for skin of rabbits.

Executive summary:

The primary irritation score was calculated by totaling the individual cumulative scores at 24, 48 and 72 hours and then dividing by the number of figures. Under the conditions of this experiment, the test material was found to cause a primary irritation score of 0.11 (max. 8.0) when applied to healthy intact rabbit skin.

Local signs (mean values from 24 to 72 hours) consisted of grade 0.11 erythema and grade 0.00 edema. The single erythema grade was reversible after 48 hours.

The test article did not cause staining of the treated skin.

No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Based on the available data, the test substance is not to be classified according to CLP (Regulation EC No.1272/2008) for effects to skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

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:

from April 24, 1996 to May 2, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Conditions: Standard Laboratory Conditions.
Air-conditioned with 10 - 15 air changes per hour and continuously monitored environment with target ranges for temperature of 20 ±3 °C and for relative humidity between 40 - 70% (values above 70% during cleaning process possible), 12 hours artificial fluorescent light/12 hours dark, music during the light period.
Accommodation: Individually in stainless steel cages with an automatic equipped with feed hoppers, drinking water bowls and wood for Diet
Diet: Pelleted standard Kliba 341 rabbit maintenance diet (batch 93/96) ad libitum from Kliba Muhlen AG, CH-4303 Kaiseraugst). Results of analysis for contaminants are included in this report.
Water: Community tap water from Itlngen, ad libitum. Results of bacteriological findings/analyses, included in this report.

Vehicle:

unchanged (no vehicle)

Controls:

other: right eye for control

Amount / concentration applied:

Solid: 0.1 g / animal (left eye only)

Duration of treatment / exposure:

one second

Observation period (in vivo):

1, 24, 48, 72 h after administration

Number of animals or in vitro replicates:

2 females and 1 male

Details on study design:

The eyes of the animals were examined for intactness once, one day prior to test article administration.
Only those animals with no signs of ocular injury or irritation were used on the test.
At treatment, 0.1 g of the test article (undiluted) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test article. The right eye remained untreated and served as the reference control.
In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission Washington, C. 20207 was used for additional control purposes (Washington, 1977).
The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion
Any findings ascertained during examination were recorded and the numerical irritation scores were assigned thereafter based upon the severity of the individual findings. Therefore, the description of observed findings may differ slightly from the respective numerical irritation scores.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

3

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Other effects:

PATHOLOGY
Necropsy
No necropsy was performed on the animals euthanized at termination of observation.
All rabbits were euthanized by an intravenous injection of NARCOREN (Rhone Merieux GmbH, D-88471 Laupheim) into the ear vein at a dose of at least 1.0 ml /kg body weight (equivalent to 160 mg sodium pentobarbitone/kg body weight) and discarded.

 

VIABILITY / MORTALITY AND CLINICAL SIGNS

No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

IRRITATION                                                                                   

PRIMID QM 1260 showed a primary irritation score of 0.00，when applied to the conjunctival sac of the rabbit eye.

COLORATION

No staining of the cornea, sclera or conjunctivae by the test article was observed.

CORROSION

No corrosion of the cornea was observed at any of the reading  times.

BODY WEIGHTS

The body weight of the animals was within the normal range of variability.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

No test-related response was observed in the study and thus, test substance is a non-irritant for eyes of rabbits.

Executive summary:

The primary irritation potential of the test article was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totaling the individual cumulative scores at 24, 48 and 72 hours and then dividing the resulting total by the number of figures. The primary irritation score was 0.00 (max. 13). No staining of the cornea, sclera or conjunctivae of the treated eyes by the test article was observed. No corrosion was observed at any of the measuring intervals. Based on the criteria of CLP (Regulation EC No. 1272/2008), test substance is not to be classified for eye irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Two studies were conducted to assess the potential toxicity to skin and eyes of rabbits following guideline and GLP principles.

The primary skin irritation potential of the test article was investigated by topical application of 0.5 g onto 6 cm² intact dorsal skin of each of three young adult rabbits. The primary irritation score was calculated by totaling the individual cumulative scores at 24, 48 and 72 hours and then dividing by the number of figures. Under the conditions of this experiment, the test substance was found to cause a primary irritation score of 0.11 (max. 8.0) when applied to healthy intact rabbit skin. Local signs (mean values from 24 to 72 hours) consisted of grade 0.11 erythema and grade 0.00 edema. They were reversible after 48 hours. The test article did not cause staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Based on the available data, the test substance is not to be classified according to CLP (Regulation EC No. 1272/2008) for skin irritation/corrosion.

Another primary irritation potential of the test article was investigated by instillation of 0.1 g into one eye of each of three young adult rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totaling the individual cumulative scores at 24, 48 and 72 hours and then dividing the resulting total by the number of figures. The primary irritation score was 0.00 (max. 13). No staining of the cornea, sclera or conjunctivae of the treated eyes by the test article was observed. No corrosion was observed at any of the measuring intervals. Based on the criteria of CLP (Regulation EC No. 1272/2008), the test substance is not to be classified for eye irritation/damage.

Justification for classification or non-classification

No adverse test-related response was observed during in vivo skin and eye irritation studies. Based on the available data, the test substance is not subject to classification for skin irritation/corrosion or eye irritation/damage according to CLP (Regulation EC No. 1272/2008).