Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-10-24 to 2012-11-23
Reliability:
1 (reliable without restriction)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
Animal Supplier: Kuiper Rabbitry (Gary, Indiana)
Animal Age/Weight: Young adults/290-400g at start of the study.
Prior to use, all animals were acclimated for at least five days. Animals were individually housed in wire mesh suspension cages. The animals were maintained on a 12-hour cycle light controlled room, at a temperature of 64° - 79°F (approximately 18°C to 26°C) and a relative humidity of 30-70%. The animals were supplied Purina Guinea Pig Chow and tap water ad libitum during both acclimation and test periods. There were no contaminants in either the feed or the water that would be expected to affect the outcome of this study.
Route:
epicutaneous, occlusive
Vehicle:
other: Walgreens Mineral Oil (Walgreens Mineral Oil EXP514 EP61188E)
Concentration / amount:
Induction: 10% concentration in mineral oil
Challenge: 5% concentration in mineral oil
Route:
epicutaneous, occlusive
Vehicle:
other: Walgreens Mineral Oil (Walgreens Mineral Oil EXP514 EP61188E)
Concentration / amount:
Induction: 10% concentration in mineral oil
Challenge: 5% concentration in mineral oil
No. of animals per dose:
20 animals
Details on study design:
Irritation Screening (Pilot Study):
The irritation potential of dimethyl octadecylphosphonate (DMOP) at levels of 50%, 25%, 10% and 5% were evaluated in one group of two animals. Four levels of test substance were evaluated per animal. Dilutions of the test substance were formulated w/w in mineral oil for all phases of the study. The position of the different concentrations of the test substance on the animals was varied to adjust for possible site-to-site variation in response. The day prior to test substance exposure, the hair was removed from each of the animal's backs using a small animal clipper. Closed patches were applied to the animals in the following manner. A 0.4 ml quantity of each test preparation was applied directly into a 25 mm Hilltop Chamber® and the chambers were secured with Micropore tape and further secured with Kendall adhesive tape. Approximately six hours later, the tape and chambers were removed.

Based upon the irritation screen results the test substance was dosed as 10% concentration for the induction phase of the study, and 5% concentration, the highest non-irritating concentration, for the challenge phase of the study.

Induction Phase:
The left shoulder of each test animal was clipped with a small animal clipper the day before exposure. The chambers were applied as previously described under the "Irritation Screening" section. Two additional induction doses were conducted following the same procedure, at weekly intervals. After the last induction exposure, the animals were left untreated for 14 days before primary challenge.

Primary Challenge Phase:
The test animals, which had three previous exposures to the test substance, were exposed to the test substance in the challenge phase 14 days after the last induction exposure. The same exposure procedure as for the "Induction Phase" was used, except the Hilltop Chambers were applied to a skin site that had not been previously exposed. Each animal received a single chamber to the clipped right shoulder.
The day following the irritation exposure all animals were scored as described under below:
The test sites were graded using the following scale:
0 = no perceptible reaction
± = slight, diffuse or ill-defined erythema
1 = slight but confluent, or moderate patchy erythema
2 = moderate erythema
3 = severe erythema with or without edema
The grading was repeated the following day. For reporting purposes, the first and second gradings were designated as 24 and 48 hour readings, respectively.

Interpretation
Grades of 1 or greater in an induced group generally indicate sensitization, provided grades of less than 1 are seen on respective control animals. If grades of 1 or greater are noted on control animals, then the reactions of respective test animals which exceed the most severe control reaction are presumed to be due to sensitization.
The results of the primary challenge and rechallenge (if performed) are expressed in terms of both incidence and severity of responses and an assessment by comparison of responses in the test group to those of the corresponding control.

Incidence: The number of animals in each group showing a specific response at either the first or second readings divided by the total number of animals tested in that group (e.g. 10/20).
Severity: The sum of the test grades divided by the total number of animals tested in a given group determined separately for both the first and second readings (e.g. 0.8-0.7). Grades of ± are equal to 0.5 for the purpose of calculating severity indices. All average grades are to be rounded to the nearest tenth of a unit, unless the severity is between 0 and 0.05, in which case the severity is rounded to the nearest hundredth of a unit.

Body Weights
Initial body weights were measured just prior to the first exposure of a respective group of animals. Final body weights were taken at the termination of the study. Final body weights were not taken for pilot animals due to their short term study participation. Animals were euthanized by carbon dioxide inhalation at the termination of the study.

Historical Positive Control Data
Historical data generated by Tox Monitor Laboratories, Inc was considered.
Challenge controls:
Challenge Controls: 5 animals
(Ten guinea pigs served as a naive control group, and remained untreated through the induction phase. Five naive control animals received only the primary challenge dose, at a 5% concentration. The five remaining guinea pigs were designated for a re-challenge, if necessary).
Positive control substance(s):
no
Remarks:
Acceptable historical control data are available
Positive control results:
Not applicable
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5% w/w
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
No abnormal observations when comparede to the control group
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5% w/w. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: No abnormal observations when comparede to the control group.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5% w/w
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No abnormal observations when compared to the control group
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5% w/w. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No abnormal observations when compared to the control group.
Reading:
1st reading
Hours after challenge:
24
Group:
other: naive control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No abnormal observations
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: naive control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No abnormal observations.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: naive control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No abnormal observations
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: naive control. Dose level: 5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: No abnormal observations.

Primary Challenge - Incidence of Responses

 

24 hours

48 hours

Means

Group

Conc.

0

±

1

2

3

0

±

1

2

3

24 h

48 h

Test

5%

16

3

1

0

0

19

1

0

0

0

0.13

0.03

Naive Control

5%

3

2

0

0

0

5

0

0

0

0

0.20

0

 

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
Sensitisation was not induced by the test meaterial.
Executive summary:

Dimethyl octadecylphosphonate (DMOP) was tested for dermal sensitization potential utilizing a Buehler Technique Guinea Pig Sensitization Protocol. The test substance was evaluated for sensitization potential by applying 0.4 ml at a 10% concentration in mineral oil directly into Hilltop Chambers® and applying them to the clipped left shoulder of twenty albino guinea pigs in the following manner: The chambers were applied to the clipped left shoulder and secured with Micropore tape and further secured with Kendall adhesive tape. Approximately six hours later, the tape and chambers were removed. Two additional induction doses were conducted following the same procedure, at weekly intervals. Two weeks after the final application the animals received a topical primary challenge dose (6 hour contact) of DMOP at 5% concentration in mineral oil on a naive site located on the right shoulder. Animals were scored for irritation at 24 and 48 hours after initiation of the primary challenge application. Ten guinea pigs served as a naive control group, and remained untreated through the induction phase. Five naive control animals received only the primary challenge dose, at a 5% concentration. The five remaining guinea pigs were designated for a re-challenge, if necessary.

Following primary challenge of DMOP at 5% concentration, the incidence of grade 1 response or greater in the test group (1 of 20) was compared to that of the naive control group (0 of 5). The incidence and severity of these responses were not significantly greater than those produced by the naive control group indicating that sensitization had not been induced.

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

In a GLP, guideline compliant study dimethyl octadecylphosphonate (also known as DMOP) was tested for dermal sensitization potential utilizing a Buehler Technique Guinea Pig Sensitization Protocol. The test substance was evaluated for sensitization potential by applying 0.4 ml at a 10% concentration in mineral oil directly into Hilltop Chambers® and applying them to the clipped left shoulder of twenty albino guinea pigs on 3 occasions at weekly intervals. Two weeks after the final application the animals received a topical primary challenge dose (6 hour contact) of DMOP at 5% concentration in mineral oil on a naive site located on the right shoulder. Animals were scored for irritation at 24 and 48 hours after initiation of the primary challenge application. Ten guinea pigs served as a naive control group, and remained untreated through the induction phase. Five naive control animals received only the primary challenge dose, at a 5% concentration. The five remaining guinea pigs were designated for a re-challenge, if necessary.

Following primary challenge of DMOP at 5% concentration, the incidence of grade 1 response or greater in the test group (1 of 20) was compared to that of the naive control group (0 of 5). The incidence and severity of these responses were not significantly greater than those produced by the naive control group indicating that sensitization had not been induced.

Conclusion for skin sensitisation

It may therefore be concluded that dimethyl octatdecylphosphonate is not a skin sensitizer based on the results from a GLP, guideline compliant in-vivo study in guinea pigs.


Justification for selection of skin sensitisation endpoint:
Key study

Justification for classification or non-classification