Nitric acid, reaction products with cyclododecanol and cyclododecanone, by-products from, high-boiling fraction

Endpoint summary

Description of key information

The test substance produced no to mild erythema by 1 and 24 hours after test substance removal. By 48 and 72 hours, all rabbits except 1 were clear of all irritation; the last rabbit exhibited moderate erythema. No edema, clinical signs of toxicity, or significant body weight losses were observed during the study.  high eye irritation was noted in the study.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 28, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted using the In Vitro International Corrositex Assay which is a standardized and quantitative in vitro corrosivity test. EU/OECD approval this type of test on July 19, 2006.

Qualifier:

according to guideline

Guideline:

other: The method to determine United nations' Packing Group

Deviations:

no

Remarks:

according to the study the testing protocol was followed.

Principles of method if other than guideline:

Corrositex uses a synthetic membrane-based or matrix dics system to determine the United Nation packing group classification of chemicals. The results are expressed as a break-through time and correlate with rabbit dermal corrosivity tests. A glass vial filled with a chemical detection fluid is capped by a" proprietary bio-barrier membrane" which is designed to mimic the effect of corrosives on living skin.

Corrositex measures the time required for a test article to pass through a hydrated collagen matrix and supporting filter membrane. As the corrosive sample passes through or destroys this bio-barrier, the underlying liquid Chemical Detection System changes color or texture. The time it takes for the sample to break through the membrane is recorded and compared to a classification chart to determine corrosivity/noncorrosivity for assignment of the proper U.N. Packing Group classification for U.S. DOT or EPA compliance.

GLP compliance:

not specified

Remarks:

GLP statement was not included in this study report, but the procedures for the tests were closely followed.

Species:

other: In Vitro test

Strain:

other: In Vitro test

Details on test animals or test system and environmental conditions:

No test animals were used in this study. Bio-barrier membrane or matrix discs were prepared and stored at 2.8 degrees celsius for at least 2 hours prior to conducting the assay.

Type of coverage:

other: the vials are open at the top and observed.

Preparation of test site:

other: 4 vials are used in this test.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Approximately 0.5 grams of the Corfree® M1

Duration of treatment / exposure:

>4 hours

Observation period:

Vials l-4 were observed for > 240 minutes. 

Number of animals:

No animals were used in this In Vitro study.

Details on study design:

The In Vitro International Corrositex Assay which is a standardized and quantitative in vitro corrosivity test is conducted in 3 steps. Step 1 is the qualifying step. Corfree® M1 (100 mg) is added to the Corrositex test tube to determine if it is compatible with the test system. The tube is shaken and allowed to stand for 1 minute. The tube is observed for a color change or change of consistency at the sample fluid interface. If the amber fluid changes color or consistency, we proceed to Step 2. If a physical change is not observed the substance is not suitable for the Corrositex system. Step 2 is where the categorize of cut-off times for the sample is established. Corfree® M1 (100 mg/vial) is added to two Corrositex test tube which are capped and shaken until mixed. If a color change is noted in either tube the color is matched to a corresponding color chart on the Corrositex Testing Protocol Poster. The appropriate category is assigned according to the color found on the poster. If no color is observed in either tube 2 drops of a confirm reagent is added to Tube B, the tube is shaken until mixed. The resulting color is matched to a corresponding color chart on the Corrositex Testing Protocol Poster. The appropriate category is assigned according to the color found on the poster. Step 3 is the classification step used to determine the appropriate Packing Group. Several vials (4) are used for sample replicate testing. There is a positive and negative control. Corfree® M1 (500 mg) is added to top of the bio-barrier disc; the timer is started the instant the test substance is applied. The vials are observed for changes in the membranes' structure by colormetrics. The category assigned and the mean value of the breakthrough time for all 4 samples replicate vials determine the packing group.

Irritant / corrosive response data:

No breakthrough occured in Vials 1-4. Under the conditions of this test, Corfree® M1 was not a corrosive substance and was assigned to non-corrosive.

Other effects:

No other effects were observed.

No other information is available on this test.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Corfree® M1 was not a corrosive substance and was assigned to non-corrosive.

Executive summary:

Dermal Irritation (DuPont, 1999): In a non-GLP, non-guideline study, a membrane disk containing the bio-barrier matrix was placed into a chemical detection system (CDS) vial. Approximately 0.5 grams of the Corfree® M1 (consisting of 46 wt% Dodecanedioic acid, 31 wt% Undecanedioic acid, 5 wt % Sebacic acid and 11 wt% other dibasic acids), ground with a mortar and pestle, was placed on the top of the disc. The vial was then observed for a change in the CDS. This procedure was followed for each of 4 test vials. Vial 5 was similarly treated with a positive control (sulfuric acid) and Vial 6 was similarly treated with a negative control (citric acid). Vials l-4 were observed for > 240 minutes. 

The test substance did not pass through any of the membranes. It was concluded that Corfree® M1 was not a corrosive substance.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

April 9, 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Only 10 mg of the solid test substance was applied to only one test animal whose eyes were left unwashed. The test was conducted in the same lab as the acute oral test, but the statement of reliability is not located on the cover page. However, the OECD guidline are mentioned in the conclusion section. Study is comparable to OECD 402 and performed without a written statement of GLP, but the lab management system is clearly stated.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

The GLP was not stated, but OECD was classification was mentioned

Principles of method if other than guideline:

Draize Method

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Young adult HM (NZW) fBR New Zealand White rabbits were received from Hare Marland, Hewitt, New Jersey. The rabbits were housed singly in suspended stainless steel, wire-mesh cages. Each rabbit was asssigned an unique identification number which was written on the inside of each rabbit's
ear. The animals were offered approximately 125 grams of PMI Nutrition International, Inc. Certfied High Fiber LabDiet 5325 daily during the study. Water wasavailable ad libtum. Rabbits were quarantined, weighted, and observed for general health for 12 days or 14 days. Animal rooms were maintained on a timer-controlled, 12-hours light and 12 hours dark cycle. Environmental conditions of the rooms were targeted for a temperature of 20 degrees celsius plus or minus one degree celsius and relative humidity of fifty percent plus or minus ten percent. Excursions outside these ranges were judged to have been of insufficient magnitude and/or duration to have adverselyaffected the validity of the study.

Vehicle:

unchanged (no vehicle)

Remarks:

ground into a fine powder as possible with a mortar and pestle

Controls:

not required

Amount / concentration applied:

Approximately 0.01 gram /one eye/rabbit

Duration of treatment / exposure:

20 seconds/both eyes rinsed with water of one rabbit and the others rabbits eyes were not washed.

Observation period (in vivo):

Approximately 20 seconds after instillation, the treated and control eyes of 1 rabbit were washed. The treated and control eyes of the remaining rabbit were not washed. The eyes of the rabbits were examined on the day of treatment and on days 1, 2, 3, and 7 following treatment.

Number of animals or in vitro replicates:

2 young adult rabbits

Details on study design:

The study was non-GLP, non-guideline. The rabbits weighed 2,778 or 3,018 g on the day of treatment. The rabbits used on the study were free of pre-existing cornea1 or conjunctival injury or irritation and were judged to be in good health. 
Approximately 0.01 g of the test substance was instilled into the lower conjunctival sac of the right eye of each rabbit

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: Avg. of 24, 48, and 72 hrs

Score:

0

Max. score:

0

Reversibility:

other: No effects observed

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: Avg. of 24, 48, and 72 hrs

Score:

0

Max. score:

0

Reversibility:

other: No effects observed

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: Avg. of 24, 48, and 72 hrs

Score:

1.3

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: Avg. of 24, 48, and 72 hrs.

Score:

0.33

Max. score:

1

Reversibility:

fully reversible

Irritant / corrosive response data:

The test substance produced moderate conjunctival redness and moderate discharge in both treated rabbit eyes. In addition, slight chemosis was observed in the treated unwashed eye, and mild chemosis and blistering on the conjunctiva and the nictitating membrane were observed in the eye washed after treatment. Both treated eyes were normal by 7 days after administration of the test substance. No clinical signs of toxicity or body weight losses were observed during the study.

No additional results are available.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance produced moderate conjunctival redness and moderate discharge in both treated rabbit eyes. In addition, slight chemosis was observed in the treated unwashed eye, and mild chemosis and blistering on the conjunctiva and the nictitating membrane were observed in the eye washed after treatment. Both treated eyes were normal by 7 days after administration of the test substance. No clinical signs of toxicity or body weight losses were observed during the study.

Executive summary:

Eye Irritation (DuPont, 1999): The Corfree® M1(consisting of 46 wt% Dodecanedioic acid, 31 wt% Undecanedioic acid, 5 wt % Sebacic acid and 11 wt% other dibasic acids) was tested for eye irritation potential in 2 young adult rabbits. The study was non-GLP, non-guideline. The rabbits weighed 2,778 or 3,018 g on the day of treatment. The rabbits used on the study were free of pre-existing cornea1 or conjunctival injury or irritation and were judged to be in good health.

 

Approximately 0.01 g of the test substance was instilled into the lower conjunctival sac of the right eye of each rabbit. Approximately 20 seconds after instillation, the treated and control eyes of 1 rabbit were washed. The treated and control eyes of the remaining rabbit were not washed. The eyes of the rabbits were examined on the day of treatment and on days 1, 2, 3, and 7 following treatment. At each of these observation periods, eyes were examined using illumination and magnification and scored for ocular reactions according to the Draize scale. Clinical signs of toxicity and body weights were periodically recorded.

 

The test substance produced moderate conjunctival redness and moderate discharge in both treated rabbit eyes. In addition, slight chemosis was observed in the treated unwashed eye, and mild chemosis and blistering on the conjunctiva and the nictitating membrane were observed in the eye washed after treatment. Both treated eyes were normal by 7 days after administration of the test substance. No clinical signs of toxicity or body weight losses were observed during the study.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Corfree® M1 was a slighty skin irritant and stained the skin of 5 rabbits yellow; however, the test sites could still be evaluated for erythema. One rabbit exhibited no dermal irritation during the study. The test substance produced no to mild erythema by 1 and 24 hours after test substance removal. By 48 and 72 hours, all rabbits except 1 were clear of all irritation; the last rabbit exhibited moderate erythema. No edema, clinical signs of toxicity, or significant body weight losses were observed during the study.

The test substance produced moderate conjunctival redness and moderate discharge in both treated rabbit eyes. In addition, slight chemosis was observed in the treated unwashed eye, and mild chemosis and blistering on the conjunctiva and the nictitating membrane were observed in the eye washed after treatment. Both treated eyes were normal by 7 days after administration of the test substance.

Justification for selection of skin irritation / corrosion endpoint:
The study was conducted using the In Vitro International Corrositex Assay which is a standardized and quantitative in vitro corrosivity test. EU/OECD
approval this type of test on July 19, 2006.

Justification for selection of eye irritation endpoint:
The test was conducted in the same lab as the acute oral test, but the statement of reliability is not located on the cover page. However, the OECD guidline are mentioned in the conclusion section. Study is comparable to OECD 402 and performed without a written statement of GLP, but the lab management system is clearly stated.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Eye Irritation:

Classified as Category 2 based on the weight of evidence between two Klimisch 2 in vivo studies, the older of which reported clear effects on the eye (with possible but unconfirmed irreversibility) while the more recent study (similar to OECD 405 with deviations) produced more minor effects that were clearly reversible within 7 days. This classification is further supported by read-across to Dodecanedioic Acid (CAS# 693-23-2), a primary constituent of the UVCB substance being registered, which is also classified as a Catergory 2 eye irritant.

Skin Irritation/Corrosion:

Not classified as corrosive. Referencing the Corrositex study by DuPont 2138 (1999), the material did not pass thru the membrane during the observation period.

Not classified as irritating. Referencing DuPont 2450 (1999), the material, after a 4 -hour application, produced no to mild erythema by 1 and 24 hours after application removal.