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Administrative data

Description of key information

-In vivo skin sensitization according to Draize (intradermal application): sensitizing (guinea pig)


-In vivo skin sensitization according to Landsteiner and Jacobs procedure (intradermal application): not sensitizing (guinea pig)


-In vivo skin sensitization, Buehler test (topical application): not sensitizing (guinea pig)


-In vivo skin sensitization, human volunteers: not sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 October - 21 November 1980
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: An intradermal sensitization test was conducted by injecting Amine CS-1135™ solution (P-1952) into male guinea pigs according to Landsteiner.and Jacobs procedure (Landsteiner, K., and J. Jacobs. "Studies on Sensitization of Animals with Simple Chemieal, Compounds." J. Exp. Med. 61:643-656, 1935).
- Short description of test conditions: A total of 10 injections was made on alternate days, three times a week, over a four week period in male guinea pigs. After each injection the site was scored. After the last injection, the animals were allowed to rest for two weeks. A challenge injection was made at a virgin site.
- Parameters analysed / observed: Erythema and edema at 24 and 48 h after injection.
GLP compliance:
yes
Type of study:
intracutaneous test
Justification for non-LLNA method:
The study was conducted before the OECD Guideline 429: Skin Sensitisation Local Lymph Node Assay came into force in 2002.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot No.of test material: IMC, Terre Haute, Indiana; lot No. 94
- Purity test:
An analytical report for CS-1135 (Lot 94) submitted with the sample showed the following analysis:

Oxadine 82.01 %
TMO 2.90 %
Water 15.00 %
ox APD 0.01 %
ox E 0.05 %

(TMO=Trimethyl oxazolidine, ox APD=Oxazolidine from amino propanediol, ox E=Oxazolidine E)
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Murphy Breeding Laboratories, Inc., Plainfield, Indiana.
- Age at study initiation: at least 4 weeks old
- Weight at study initiation: 250 to 300 g
- Housing: housed as five per cage during and after each treatment.
- Diet: The animals were fed Purina Certified Guinea Pig Chow #5026, ad libitum. Each utilized lot was identified and dated.
- Water: The tap water was supplied ad libitum. Every quarter the animals' drinking water was analyzed to ensure that the levels of contaminants are equal to or less than the recommended levels as per the Primary Drinking water Regulations.
- Acclimation period: Allowed to acclimatize to the laboratory. The guina pigs used in this study were purchased at least one week before the test
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
9 x 0.1 ml of 0.1 % solution of P-1952 in saline
1 x 0.05 ml of 0.1 % solution of P-1952 in saline
Day(s)/duration:
28 days
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1 ml of 0.05 % solution of P-1952 in saline
Day(s)/duration:
2
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10x
- Exposure period: 24 h
- Test groups: Group IX was intradermally injected once with 0.05 ml of 0.1% solution of P-1952 in saline. After 48 hours, the intradermal injection procedure was repeated for each group with 0.1 ml of each solution two or three times a week until a total of 10 injections have been made.
- Control groups: Group X (positive control) was similarly injected with 0.05 ml of 0.3% dinitrochlorobenzene (DNCB) solution (solubilized in minimum volume of alcohol and made to volume with saline). Group XI (negative control) was injected with 0.05 ml of saline. After 48 hours, the intradermal injection procedure was repeated for the control groups with 0.1 ml of each solution two or three times a week until a total of 10 injections have been made.
- Site: back and flank of the animals
- Frequecy of applications: 2-3 d
- Duration: 28 d
- Readings: After 24 hours and 48 hours the injected sites were scored for erythema and edema, according to Draize.

B. CHALLENGE EXPOSURE
- Time between Induction and Challenge: 14 d after 10th induction injection
- No. of exposures: 1x
- Day(s) of challenge: 2 d
- Test groups: Group IX (treatment group) were challenged with 0.1 ml of 0.05% and 0.1 % solution of P-1952 in saline
- Negative Control group XI were challenged with 0.1 ml of saline
- Positive Control group: Group X animals were challenged with 0.03 and 0.3 % DNCB solution (solubilized in minimum volume of acetone and made to volume with saline).
- Readings: Readings were made 24 and 48 h after challenge. The injected sites were scored for inflammatory skin reactions (erythema and edema). The material is considered a sensitizer, if at challenge the number of animals showing skin reactions are higher in the treatment group (IX) than in the negative control group (XI). The positive control group serves as an internal control for the test.
- Scoring: The skin irritation for erythema, edema or other lesions will be scored according to Draize ('Appraisal of the Safety of Chemica1s in Foods, Drugs, and Cosmetics. 'Association of Food and Drug Officials of the United States, pp 46-59, 1959).
Challenge controls:
0.03 % and 0.3 % DCNB solution (solubilized in minimum volume of alcohol and made to volume with saline)
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene (DCNB)
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 % of P-1952
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1 % of P-1952
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.05 % of P-1952
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.05 % of P-1952
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.3 % of DCNB
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.3 % of DCNB
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.03 % of DCNB
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.03 % of DCNB
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.05 % of P-1952
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.05 % of P-1952
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.01 % of P-1952
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.01 of P-1952
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. reacted/challenged
Remarks on result:
no indication of skin sensitisation

During the induction phase the guinea pigs in Group IX showed some skin reactions, so that the last (10th) injection was made with 0.05% solution of P-1952. None of the animals in Group XI showed any skin reactions. The animals in Group X showed mild to necrotic skin reactions during the entire induction period.

At challenge, Group IX (treatment group) and Group XI (negative control) guinea pigs were intradermally injected with 0.05 and 0.01% solution of P-1952, and none of the animals in either group showed any skin reactions. In the positive control (Group X) at 24 hr, seven animals at 0.03% and all animals at 0.3% showed skin reactions. At 48 hours only two animals at 0.3% showed skin reactions.

Interpretation of results:
GHS criteria not met
Conclusions:
Amine CS-113S™ (P-19S2) was a nonsensitizer to the guinea pigs under the conditions of this test. The positive control DNCB gave an expected positive response.
The toxicity index for Amine CS-113S™ (P-1952) is: Sensitization: Intradermally a nonsensitizer. (Guinea Pig)
Endpoint:
skin sensitisation, other
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 April - 08 June 1979
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
other: Shelanski (Combination method)
Deviations:
not specified
Principles of method if other than guideline:
- Principle of test: Shelanski (Combination method)
- Short description of test conditions:
A total of 105 individuals was selected to participate in this evaluation. The procedure is a double-blin
d evaluation of the test material in a randomy selected group from the local population.
Induction was done through a series of twelve consecutive daily applications, each of twenty-four h
ours duration, was scheduled to be carried out during the induction period (weeks #1, 2 and 3). In
week #1 and #2 the test material was applied in a concentration of 3.0 % w/v in water; in week #3 the
test material was applied in a concentration of 0.3 % w/v in water.
Challenge was done through one application with a concentration of 0.3 % w/v of the test material in
water on virgin sites during the challenge week (week #6).
An additional challenge application was done with 2 individuals with a concentration 0.1 % w/v of the
test substance in water (week #8).
Site definition: A site on the arm of each individual was selected and identified for contact with the
test material.
Patch definition: Specially prepared Parke-Davis Readi-Bandages werde used in this procedure. 0.2
ml of the test material was applied to the webril pads of occlusive Readi-Bandages. The patches were
then applied to the sites.
- Parameters analysed / observed:
Direct effects: Immediate Primary Irritation and/or Fatigue or Cumulative Primary Irritation
Indirect effects (Hypersensitivity): Immediate Reaction Type (Histamine release, phenomenon,
wheal and flare, urticaria, Arthus penomenon), Delayed Reaction Type (Macular or maculo-papular
eruptions, induration, itching)
GLP compliance:
not specified
Type of study:
patch test
Justification for non-LLNA method:
The study was conducted before the OECD Guideline 429: Skin Sensitisation Local Lymph Node Assay came into force in 2002.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot No: Received from International Minerals and Chemical Corporation at 16 April 1979,
Lot No. 55
- Description: clear liquid
- Purity: 78%
Species:
other: human
Sex:
male/female
Details on test animals and environmental conditions:
TESTED POPULATION
- Source: Randomly selected group from the local population
Adults (18 years and older) from local population were recruited to participate.
Criteria for initial qualification:
1. Willingness to cooperate
2. Dependability and perserverance.
3. Ability to understand the purpose of the procedure and what was required of him or her.
4. Ability to understand the risks involved and to make a reasonable judgment to participate.
5. Ability to understand the items in the consent form which he or she was required to sign before the
start of the study.
Exclusion Criteria:
A history of past and present health status and medication intake was obtained from each of the
individuals being considered a brief physical examination was performed in order to detect and eli
minate any who evidenced any finding which could be considered a basis for exclusion.
Candidates were exeluded for any one of the following reasons:
1. Systemic illnes which might have contra-indicated participation.
2. Skin disease with manifestions wich might be confused with effects of the test material.
3. Intake of medications which might augment or impede the irritant effects of the test material.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
3% w/v solution
No. with + reactions:
1
Total no. in group:
101
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
3% w/v solution
No. with + reactions:
1
Total no. in group:
100
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
3% w/v solution
No. with + reactions:
0
Total no. in group:
101
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
other: Rechallenge of two individuals that showed positive reaction on first challenge
Dose level:
0.1 % w/v
No. with + reactions:
0
Total no. in group:
2
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: rechallenge 2nd reading
Hours after challenge:
48
Group:
other: Rechallenge of two individuals that showed positive reaction on first challenge
Dose level:
0.1% w/v
No. with + reactions:
0
Total no. in group:
2
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: rechallenge 3rd reading
Hours after challenge:
72
Group:
other: Rechallenge of two individuals that showed positive reaction on first challenge
No. with + reactions:
0
Total no. in group:
2
Remarks on result:
no indication of skin sensitisation

No significant irritation was recorded as a result of the first application.

The presence of visible irritation after two or more applications indicates that the sample material tes

ted at 3.0% w/v emulsion in water did excert a primary irritant effect of the cumulative type in 70.3 %

of the individuals under test.

The presence of visible irritation after two or more applications on week #3 indicates that the sample

material tested at 0.3 w/v emulsion in water did excert a primary irritant effect of the cumulative type

in 6.9 % of the individuals under test.

Challenge period: 0.3% w/v emulsion in water

The test material, tested at 0.3% w/v emulsion in water was well tolerated by all but two panelists.

Additional Challenge period: 0.1% w/v emulsion in water

The absence of any significant reaction in the two panelists indicate that this dilution of the test material, 0.1% w/v solution in water, was incapable of eliciting a response wich could be interpreted as evidence that sensitization has occured.

Interpretation of results:
GHS criteria not met
Conclusions:
The results indicate that, though a 3.05 w/v dilution of the test material was capable of irritating the skin of 70.3% of the test panel, it was not capable of eliciting a state of hypersensitivity in any of the individuals.
The 95 percentile confidence limits, where CS-1135 will not elicite any sensitization reactions are 96.41 to 100%, for n = 101.
Executive summary:

Amine CS-1135 (P-1952, 4,4-dimethyl-1,3-oxazolidine or Oxazolidine A 78% plus water 22% by weight) Lot No. 55, was submitted to Product Investigations, Inc., Conshohocken, PA, for potential assessment of dermal irritation and sensitization hazard in human volunteers. A series of twelve, 24 hr applications, four applications per week of Amine CS-1135 were applied to the intact skin. Each application consisted of 0.2 m1 solution of Amine CS-1135 under an occlusive patch.

Initially, a 3.0 % solution of Amine CS-1135 was applied but by the end of the second week, 60% of the subjects were exhibiting irritation at the application site. Thus, for the third week repeat applications of the concentration of CS-1135 was reduced to 0.3%. After two weeks of rest a virgin site was challenged with 0.3% CS-1135 solution.

Only two subjects out of 101 showed any skin reaction within the four-day observation period. The same two subjects upon rechallenge with a 0.1% CS-1135 solution at a virgin site showed no skin reaction. A 3% CS-1135 solution produces fatiguing and irritation to the human skin but it does not elicite a sensitization reaction. The 95 percentile confidence limits, where CS-1135 will not elicite any sensitization reactions are 96.41 to 100%, for n = 101.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 May - 29 June 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
- Principle of test: A topical contact sensitization test was conducted in the male guinea pigs according to Buehler's procedure (Buehler, E. V. "Delayed Contact Hypersensitivity in the Guinea Pig," Arch. Dermat. 91: 171-75, 1965).
- Short description of test conditions: Guinea pigs were topically treated with the test substance, applied under an occlusive patch. After 24 h the patches were removed and the treated skin sites were scored at 24 and 48 h for erythema and edema according to Draize. ("Appraisal of the Safety of Chemicals in Foods, Drugs, and cosmetics." Assoc. of Food & Drug Officials of the United States, p. 48, 1957). At 48 h the topical application procedure was repeated with each group of animals two to three times a week until a total of 10 applications have been made. After 14 d of rest animals in each group were challenged with their respective material. After 24 and 48 h the challenged areas were scored for inflammatory skin reactions (erythema and edema) according to Draize.
- Parameters analysed / observed: Erythema/Edema
GLP compliance:
not specified
Type of study:
Buehler test
Justification for non-LLNA method:
The study was conducted before the OECD Guideline 429: Skin Sensitisation Local Lymph Node Assay came into force in 2002.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot No.of test material:
IMC, Terre Haute, Indiana; lot No. 94
- Purity test:
An analytical report for CS-1135 (Lot 94) submitted with the sample showed the following analysis:

Oxadine 82.01 %
TMO 2.90 %
Water 15.00 %
ox APD 0.01 %
ox E 0.05 %

(TMO=Trimethyl oxazolidine, ox APD=Oxazolidine from amino propanediol, ox E=Oxazolidine E)
Species:
guinea pig
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 250 to 300 g
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
10 x 0.5 ml of a 5% solution
Day(s)/duration:
28 days
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
0.5 ml of a 0.5% / 1.5% solution
Day(s)/duration:
1 d
Adequacy of challenge:
not specified
No. of animals per dose:
10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10x
- Exposure period: 24 h
- Test groups: Group IV (treatment group) was topically treated with 0.5 ml of a 5% solution of P-1952 in saline, applied under an occlusive patch. 48 h after start of the first application, the topical application procedure was repeated with each group of animals two to three times a week until a total of 10 applications have been made.
- Control groups: Group VI (positive control) was similarly treated with 0.5 ml of 0.3% dinitrochlorobenzene solution (DNCB solubilized in minimum volume of alcohol and made to volume with saline). Group X and Group VIII (negative controls) consisting of ten animals each, were similarly treated with 0.5 ml of saline. 48 h after start of the first application, the topical application procedure was repeated with the control group of animals two to three times a week until a total of 10 applications have been made.
- Site: backs and flanks (shaved)
- Frequency of applications: 2-3 d
- Duration: 28 d
- Readings: After 24 and 48 h of every induction, the treated skin sites were scored at 24 and 48 h for erythema and edema according to Draize.

B. CHALLENGE EXPOSURE
- Time between Induction and Challenge: 14 d
- No. of exposures: 1x
- Length of challenge: 1 d
- Test groups: Group IV was challenged with a topical treatment of 0.5 ml 5% solution of P-1952 in saline, applied under an occlusive patch.
- Control group: Group VI was challenged with 0.5 ml of 0.3% dinitrochlorobenzene solution (DNCB solubilized in minimum volume of alcohol and made to volume with saline). Group X was challenged with 0.5 ml 5% solution of P-1952 in saline. Group VIII was challenged with 0.5 ml of 0.3% dinitrochlorobenzene solution.
- Evaluation: After 24 and 48 h the treated skin sites were scored at 24 and 48 h for erythema and edema according to Draize. The material is considered a sensitizer if the skin reaction scores are higher in the treatment group thanthat in the negative control group. The positive control group serves as an internal control for the test.
Positive control substance(s):
yes
Remarks:
0.3% dinitrochlorobenzene (DNCB solubilized in minimum volume of alcohol and made to volume with saline)
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5 % Test material
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
No. Reacted
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5 % test material
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. Reacted
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1.5 % test material
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
No. Reacted
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1.5 % test material
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. Reacted
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.3 % of DNCB
No. with + reactions:
9
Total no. in group:
9
Clinical observations:
No. Reacted
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.3 % of DNCB
No. with + reactions:
7
Total no. in group:
9
Clinical observations:
No. Reacted
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5 % test material
No. with + reactions:
1
Total no. in group:
9
Clinical observations:
No. Reacted
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5 % of test material
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
No. Reacted
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1.5 % test material
No. with + reactions:
1
Total no. in group:
9
Clinical observations:
No. Reacted
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1.5 % test material
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
No. Reacted
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.3 % of DNCB
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
No. Reacted
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.3 % of DNCB
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No. Reacted
Remarks on result:
no indication of skin sensitisation

After the first two topical applications, the guinea pigs in the treatment group (Group IV) showed mild skin reactions. The last 8 treatments were made with a 2.5% solution. The animals in the other two groups showed none to very mild skin reactions during the induction period. Animal #71 in Group VI died of lung infection after the second application and another animal (#99) in Group X also died of lung infection after the last application.

When challenged with 0.5 and 1.5% solution of test material, one guinea pig in Group IV and one in Group X (negative control) showed some skin reactions at 24 hours. At 48 hours none of the animals showed any skin reactions. When challenged with 0.3% DNCB solution, all the animals in Group VI and four in Group VIII showed skin reactions, but at 48 hours only seven animals in Group VI and none in Group VIII showed any reactions.

Interpretation of results:
GHS criteria not met
Conclusions:
Topically Amine CS-113S™ (Oxadine A™, P-19S2) was a nonsensitizer in the guinea pig test.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: A predictive test to determine the potential of the material CS-1135 to produce allergic contact dermatitis was carried out using the general procedure of Draize, et al.
Draize, J.H., 1959, "Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics," Dermal Toxicity, p. 46, Austin, Texas, Association of Food and Drug Officials of the United States, Texas State Departrnent of Health.
- Short description of test conditions: The test solutions were administered intracutaneously over a 21-day period to a group of 10 guinea pigs. Fourteen days following the last dose, the animals were tested for drug sensitization by administering test solutions intracutaneously. Contemporary positive and negative controls consisted of horse serum and saline treated animals.
- Parameters analysed / observed: Readings for the sensitization reaction were made at 24 hrs following the challenge. Numerical evaluations arbitrarily assigned for scoring the height, diameter and color of the skin reaction were compared with the average of the readings taken after each of the original 10 insult injections.
GLP compliance:
not specified
Type of study:
Draize test
Justification for non-LLNA method:
The study was conducted before the OECD Guideline 429: Skin Sensitisation Local Lymph Node Assay came into force in 2002.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: 37
- Composition: CS-1135 contains 85-90 % of 4,4-dimethyloxazolidine
Species:
guinea pig
Strain:
Hartley
Remarks:
Albino
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CAMM Co., Wayne, N. J.,
- Females: not specified
- Age at study initiation: not specified
- Weight at study initiation: 240 - 300 g
- Housing: suspended wire cages either individually or by groups depending upon the protocol requirement
- Diet: pelleted guina pig ration (Ralston-Purina, Guinea Pig Chow) with stabilized ascorbic acid
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24±4
- Air changes: dynamic filtered air flow by central control system
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.05 ml of 0.3% w/v CS-1135
Day(s)/duration:
10
Adequacy of induction:
not specified
No.:
#1
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.05 ml of 0.3% w/v CS-1135
Day(s)/duration:
24 h
Adequacy of challenge:
not specified
No. of animals per dose:
10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10x
- Exposure period: 21 d
- Test groups: 0.05 ml of the test substance as a first dose, 0.1 ml of the test substance for the other nine doses. Each dose was administered at a new site.
- Control groups: see test groups but with positive control (horse serum) or negative control (0.9 % Saline) instead of test material
- Site: back and flanks (hair removed through clipping)
- Readings: Readings were made of each injection site 24 h following each of the injections. Reactions were recorded using an arbitrary nurnerical evaluation index to score diameter, height, and color of the responses to the injection. For the purposes of this test the following index was used:

Response Index Scale
No reaction 0
Very Slight 1
Slight 2
Mild 4
Moderate 6
Severe 8

B. CHALLENGE EXPOSURE
- Time between Induction and Challenge: 14 d after 10th induction injection
- No. of exposures: 1
- Day(s) of challenge: 1
- Test groups: 0.05 ml of the test substance
- Control group: see test groups but with positive control (horse serum) or negative control (0.9 % Saline) instead of test material
- Readings: Readings were made 24 h after challenge. The areas were examined and readings made of the diameter, height and color of the reaction. The reactions were scored according to the index outlined above.

C. RECORDING AND INTERPRETATION OF THE DATA

a. A daily record was maintained of the individual animal response in each of the three groups for diameter, height and color of the reaction. A daily average for each group was calculated for each of the 10 insult injections. Likewise, the average 10 daily readings were cornbined to obtain an overall average response for the 10 day insult test period. A group average was calculated for the 24 hr reactions following the retest injection.
b. In analyzing the results, a comparison of the reaction following the challenge -or retest dose is made with the average of the readings taken after each of the original 10 injections. Should the value for retest reading be substantially higher than for the average of the 10 original readings, the substance is considered to have produced a sensitizing reaction. The degree of sensitization is proportional to the increase in the final reading compared to the average of the readings following the 10 original doses.
Positive control substance(s):
yes
Remarks:
Horse serum (Difco)
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Diameter of skin response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Height of skin response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Color of skin response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Average skin response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 %
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
Diameter of skin response
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 %
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Height of skin response
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 %
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
Color of skin response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.3 %
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Average skin response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Diameter of skin response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
Height of skin response
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Color of skin reponse
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
Average of skin response
Remarks on result:
no indication of skin sensitisation

Induction:

The CS-1135, 0.3% solution in isotonic sodiurn chloride administered using 0.1 ml, intracutaneously, produced significant skin irritation resulting in edema and erythema within 24 to 48 hours and severe tissue necrosis with eschar formation within 72 hours. This was observed in the 9 insult doses of 0.1 ml; it was not observed following the first insult dose of 0.05 ml.

The combined average score of the 10 induction doses for each test material are shown below

   

 Skin response         
 Test Group  Treatment  Diameter  Height  Color  Average
 I  Saline 0.9 %  0.06  0.11  0.24  0.14
 II  CS-1135 (Batch 37) 0.3 %  0.58  0.55  0.88  0.67
 III  Horse serum  0.39  0.52  0.9 0.6

 Challenge:

Seven of 10 animals in Test Group III, horse serum, showed necrosis at the retest injection sites at 48 hrs. One of 10 in Test Group II, CS-1135, had necrosis at retest injection site. No animals in saline control group had necrosis.

Cornparison of the above values reveals that CS-1135, 0.3% solution, produced a skin response which, on average, was substantially greater than that resulting from the insult treatments. Thus, this material is capable of producing sensitization when administered to the guinea pig. Horse serum, a known sensitizing agent, produced a sensitizing reaction.

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The average values found following the challenge were found to be substantially higher than the average value af the original 10 readings with 0.3% CS-1135. Thus, under the conditions of this test, CS-1135 produced sensitization when administered intracutaneously to the guinea pig.
Executive summary:

CS-1135 (P-1952) Oxazolidine-A contains as the active principle, 4-4 dimethyloxazolidine which comprises 85-90% by weight of the product. This is hereinafter referred to as CS-1135. CS-1135 was tested as a 0.3 percent solution. Isotonic saline was used as the diluent.

The test solutions were administered intracutaneously over a 2l-day period to a group of 10 guinea pigs. Fourteen days following the last dose, the animals were tested for drug sensitization by administering test solutions intracutaneously. Contemporary positive and negative controls consisted of horse serum and saline treated animals.

Readings for the sensitization reaction were made at 24 h following the challenge. Numerical evaluations arbitrarily assigned for scoring the height, diameter and color of the skin reaction were compared with the average of the readings taken after each of the original 10 insult injections.

The average values found following the challenge were found to be substantially higher than the average value af the original 10 readings with 0.3% CS-1135. Thus, under the conditions of this test, CS-1135 produced sensitization when administered intracutaneously to the guinea pig.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

4-4 dimethyloxazolidine produced sensitization in one study when administered intracutaneously to the guinea pig, but induced no sensitization in a second study.

Topical application of 4-4 dimethyloxazolidine to guinea pigs (Buehler test) did not induce skin sensitization

In a study performed with human volunteers, no sensitization reaction was observed after reapeated topical application.

Therefore, 4-4 dimethyloxazolidine (CAS 51200-87-4) does not need to be classified as skin sensitizer according to the CLP Regulation (EC) No 1272/2008 and amendments.