Carbamic acid, [(1S,2S)-3-chloro-2-hydroxy-1-(phenylmethyl)propyl]-, methyl ester

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

in vitro

Type of information:

experimental study

Adequacy of study:

other information

Study period:

December 3, 1997 to March 13, 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Good Laboratory Practice, The United Kingdom Compliance Programme, Department of Health 1989 and subsequently the United Kingdom Good Laboratory Practice Regulations 1997, Statutory Instrument No. 654. EC Council Directive, 87/18 EEC of 18 December 1986, (No. L 15/29). Good Laboratory Practice in the testing of Chemicals OECD, ISBN 92-64-12367-9, Paris 1982, subsequently republished OECD Environment Monograph No. 45, 1992.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

EC Council Directive, 87/18 EEC of 18 December 1986, (No. L 15/29). Good Laboratory Practice in the testing of Chemicals OECD, ISBN 92-64-12367-9, Paris 1982, subsequently republished OECD Environment Monograph No. 45, 1992.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Chlorohydrine

IUPAC Name:

Chlorohydrine

Constituent 2

Reference substance name:

(l5,25)-(1-benzyl-3-chloro-2-hydroxy-propyl)- carbamic acid methyl ester

IUPAC Name:

(l5,25)-(1-benzyl-3-chloro-2-hydroxy-propyl)- carbamic acid methyl ester

Details on test material:

Identity: Chlorohydrine
Chemical name: (l5,25)-(1-benzyl-3-chloro-2-hydroxy-propyl)- carbamic acid methyl ester
Intended use: Chemical intermediate
Appearance: White powder
Storage conditions: ca. 4°C in the dark
Expiry: Assumed to be stable for six months from receipt
Date received: 17 July 1997

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

other: absolute alcohol

Concentration:

5, 10 and 20% w/w in alcohol

No. of animals per dose:

4 mice

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: na, 0.8, 0.7 and 0.9

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

TABLE 1 Group dpm/node and test/control ratios Group Concentration dpm number of dpm/node test/control + = positive % w/w lymph nodes ratio - = negative 1 Control 4523 8 565 na na 2 5 3469 8 434 0.8 - 3 10 3029 8 379 0.77 - 4 20 4276 8 535 0.9 - Vehicle = absolute alcohol Test/control ratio of 3 or greater indicates a positive result na Not applicable

Any other information on results incl. tables

In this assay the test/control ratios obtained for 5, 10 and 20% concentrations applied were 0.8, 0.7 and 0.9 respectively which indicates that Chlorohydrine did not show the potential to induce skin sensitisation (delayed contact hypersensitivity).

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

Under the test conditions, Chlorohydrine was not considered a skin sensitizer.

Executive summary:

The study was performed to assess the skin sensitisation potential of Chlorohydrine  using the murine local lymph node assay (LLNA). The assay can be used as a first stage assessment of skin sensitisation potential as indicated in the OECD Guideline for Testing of Chemicals No. 406 "Skin Sensitisation". Adopted 17 July 1992. The assay has undergone validation and has been shown to reliably detect substances that are moderate to strong sensitisers.

 

The method followed was that described in KIMBER I, HILTON J and WEISENBERGER C (1989) The murine local lymph node assay for identification of contact allergens: A preliminary evaluation of in situ measurement of lymphocyte proliferation Contact Dermatitis 21 215-220 and BASKETTER D.A. and SCHOLES E.W. (1992) Comparison of the local lymph node assay with the guinea-pig maximisation test for the detection of a range of contact allergens. Food and Chemical Toxicology 30, 65-69.

 

Groups of four mice were used in this study at three dosage levels and a vehicle control. Dosages were selected as follows: 5, 10 and 20% w/w in absolute alcohol

 

Each group of mice was treated by daily application of 25 µl of each of one of these three concentrations, and vehicle control, to the dorsal surface of both ears for three consecutive days.

 

The proliferative response of the lymph node cells (LNC) from the draining auricular lymph nodes was assessed five days following the initial application, by measurement of the incorporation or 3H-Thymidine by beta-scintillation counting of LNC suspensions. The response was expressed as radioactive disintegrations per minute per lymph node (dpm/node) and as the ratio of 3HTdR incorporation into LNC of test nodes relative to that recorded for control nodes (test/control ratio).

 

The test substance is regarded as a sensitiser if at least one concentration of the chemical results in a three-fold greater increase in 3HTdR incorporation compared to control values. In this assay the test/control ratios obtained for 5, 10 and 20% concentrations applied were 0.8, 0.7 and 0.9 respectively which indicates that Chlorohydrine did not show the potential to induce skin sensitisation (delayed contact hypersensitivity).

Conclusion

Therefore, under the test conditions, Chlorohydrine was not considered a skin sensitizer.