Methyl hydrogen octadecylphosphonate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Remarks:

Modified Beuhler Design

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

Buehler test

Justification for non-LLNA method:

A Buehler assay was conducted for R&D purposes in 2004 and in the interest of animal welfare it was considered unethical to run a LLNA.

Test material

Test material information

Constituent 1

Reference substance name:

Methyl hydrogen octadecylphosphonate

EC Number:

246-905-6

EC Name:

Methyl hydrogen octadecylphosphonate

Cas Number:

25371-55-5

Molecular formula:

C19H41O3P

IUPAC Name:

methoxy(octadecyl)phosphinic acid

impurity 1

Reference substance name:

Octadecylphosphonic acid

EC Number:

225-216-4

EC Name:

Octadecylphosphonic acid

Cas Number:

4724-47-4

Molecular formula:

C18H39O3P

IUPAC Name:

octadecylphosphonic acid

impurity 2

Reference substance name:

Dimethyl octadecylphosphonate

EC Number:

246-904-0

EC Name:

Dimethyl octadecylphosphonate

Cas Number:

25371-54-4

Molecular formula:

C20H43O3P

IUPAC Name:

dimethyl octadecylphosphonate

Test material form:

solid

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

Animals were housed individually in suspended stainless steel cages. All housing and care were based on the standards recommended by the Guide for hte Care and Use of Laboratory Animals. PMI Cerified Guinea Pig Chow and municipal tap water treated by reverse osmosis was available ad libitum throughout the studyENVIRONMENTAL CONDITIONS:Room Temperature: 18-22 ° CRelative Humidity: 36-68% Light Cycle: 12-hour light /12-hour dark cycleVentilation: 10-15 air changes /hour

Study design: in vivo (non-LLNA)

No. of animals per dose:

10/sex/dose

Details on study design:

Ten male and ten females were topically treated with 2.% MMOP in propylene glycol, once per week for three consecutive weeks. Following a two-week rest period, a challenge was performed wherbu the 20 test and ten previously untreated ontrol guinea pigs were topically treated with 0.1 % w/v MMOP in propylene glycol. Challenge responses in the test animals were compared with those of the challenge control animals

Challenge controls:

Ten previously untreated (naive) challenge control guinea pigs were topically treated with 0.1% w/v MMOP in propylene glycol.

Positive control substance(s):

yes

Remarks:

A α-Hexyclcinnamaldehyde (HCA)

Study design: in vivo (LLNA)

Vehicle:

propylene glycol

Concentration:

Topical application: 2.5% MMOP in propylene glycolChallenge application: 0.1% w/v MMOP in propylene glycol

No. of animals per dose:

10 animals/sex/dose

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

0

Total no. in group:

20

Results 2

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1%

No. with + reactions:

1

Total no. in group:

20

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.1%

No. with + reactions:

0

Total no. in group:

10

Results 4

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.1%

No. with + reactions:

0

Total no. in group:

10

Results 5

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

2.5%

No. with + reactions:

10

Total no. in group:

10

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

0/20 animals were sensitized during the course of this study indicating that sensitization has not been induced after eposure to the test item.

Executive summary:

The dermal sensitization potential of MMOP was evaluated in Hartley-derived albino guinea pigs. Ten male and tem female guinea pigs were topically treated with 2.5% w/v MMOP in propylene glycol, once per week, for three consecutive weeks. Following a two-week rest period, a challenge was performed whereby the 20 test and 10 previosuly untreated (naive) challenge control guinea pigs were topically treated with 0.1% w/v MMOP in propylene glycol. Challenge responses in the test animals were compared with those of the challenge control animals. A α-Hexylcinnamaldehyde positive control group consisting of ten HCA test and ten HCA control guinea pigs was included in the study. The HCA test animals received a 5.0% w/v HCA in ethanol for induction and 2.5% and 1.0% HCA in acetone for challenge.

Following challenge, dermal reactions in the test animals were limited to score of 0 to ± at the 24 -hour scoring interval. At the 48 hour scoring interval a score of 1 was noted in 1/20 test animals. All remaining test and challenge control animals had score of 0 to ±.

Following challenge with HCA, 10/10 HCA test animals were noted to have a stronger dermal response than was observed in the corresponding HCA control animals. The results of the HCA positive control study demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitizers.

0/20 test animals had a positive response 24 hours after challenge but by the 48 hour observation point 1/20 test animals had a positive reaction. Under the classification criteria documented in the Classification, labelling and packaging regulation (EC)2382/2008, this substance is not a skin sensitizer.