1,2,3-trichloropropane

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: - pre OECD, but generally compliant to OECD TG 406 as at 1980 - GLP compliant - study only available as summary from the SIDS report - reliability score copied from the SIDS report without further assessment

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Reference 2

Reference Type:

secondary source

Title:

SIDS INITIAL ASSESSMENT REPORT For SIAM 18 - 1,2,3-Trichloropropane

Author:

OECD

Year:

2004

Bibliographic source:

Published OECD SIDS initial assessments of HPV chemicals: http://www.oecd.org/document/63/0,3343,en_2649_34379_1897983_1_1_1_1,00.html

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

Buehler Test

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: NAS Publication 1138 dtd 1977

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A valid Buehler test conducted comparable to guideline, which is reliable and adequate for classification and labelling purposes. Potency estimation is not mandatory when existing guideline and GLP conforming data are available, which were conducted before the new annex of the REACH Regulation entered into force. Moreover, no indication for skin sensitisation was observed in this study, thus, no dose response information is needed. For this reason and for reasons of animal welfare no additional LLNA was conducted.

Test material

Test material information

Constituent 1

Reference substance name:

1,2,3-trichloropropane

EC Number:

202-486-1

EC Name:

1,2,3-trichloropropane

Cas Number:

96-18-4

Molecular formula:

C3H5Cl3

IUPAC Name:

1,2,3-trichloropropane

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Camm Research Lab
- Age at study initiation: young adults
- Weight at study initiation: not stated in the SIDS report study summary
- no further details given not in the SIDS report study summary

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Induction 2

Concentration / amount:

details not given in the SIDS report study summary

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Challenge 2

Concentration / amount:

details not given in the SIDS report study summary

No. of animals per dose:

5 males and 5 females

Details on study design:

RANGE FINDING TESTS: 0.5 mL of 1,2,3-trichloropropane was reported to be the highest not irritating level as determined in a pretest. No further details given in the SIDS report study summary.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 (day 2, 9, 26)
- Exposure period: 30 d in total, exposures at 3 days (see above)
- Test groups: two test groups - one for sensitization and one for irritation (the irritation group was not treated with the test item during the induction period = naive or "challenge" control group).
- Control group: two control groups - a vehicle control group (corn oil) and a positive control group
Comment: Please note that in the treatment groups the substance was applied as neat liquid. Nevertheless the "vehicle" control groups was treated with corn oil
- Site: laterally from the midline of the back on the left front quadrant of the exposure areas with the gauze pads adjacent to, but not overlapping, the midline of the backs
- Frequency of applications: 3 times (see above)
- Duration: 6 h
- Concentrations: treatment groups (sensitization group only): 0.5 mL of neat 1,2,3-trichloropropane; control groups: negative: details not given in the SIDS report study summary, positive: 0.1% 2,4 DNCB, but solvent and amount not given in the SIDS report study summary.
The amount of 1,2,3-trichloropropane was reported to be the highest not irritating level as determined in a pretest

B. CHALLENGE EXPOSURE
- No. of exposures: once
- Day(s) of challenge: d 30, 28 d after first induction exposure
- Exposure period: not applicable
- Test groups: two test groups - one for sensitization and one for irritation (both treated with the test item)
- Control group: two control groups - a vehicle control group (corn oil) and a positive control group
- Site: different to induction site, laterally on the right rear quadrant
- Concentrations: treatment groups: 0.5 mL of neat 1,2,3-trichloropropane; control groups: negative: details not given in the SIDS report study summary, positive: 0.1% 2,4 DNCB, but solvent and amount not given in the SIDS report study summary.
The amount of 1,2,3-trichloropropane was reported to be the highest not irritating level as determined in a pretest
- Evaluation (hr after challenge): 24 and 48 h

Scoring was conducted using the Draize score system

Challenge controls:

an average Draize score of only 0.1 was produced by the treatment of naive (uninduced) animals (5 males and 5 females)

Positive control substance(s):

yes

Remarks:

DNCB (Dinitrochlorobenzene)

Results and discussion

Positive control results:

Sensitivity of the guinea pigs to the experimental procedure was confirmed with known human sensitizers: DNCB (2,4-dinitro chlorobenzene).

In vivo (non-LLNA)

Results

Results 1

Reading:

other: details not given in the SIDS report study summary

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5 mL neat 1,2,3-trichloropropane

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Results 2

Reading:

other: details not given in the SIDS report study summary

Hours after challenge:

24

Group:

negative control

Dose level:

induction: corn oil; challenge: 0.5 mL neat 1,2,3-trichloropropane

No. with + reactions:

0

Total no. in group:

5

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

1,2,3-trichloropropane was tested for its skin sensitizing properties using the Buehler Test with male and female Dunkin-Hartley guinea pigs in general compliance to OECD TG 406 as at 1980.
Based on the derived result 1,2,3-trichloropropane is not a skin sensitizer in this test system.

Executive summary:

In the present study (Shell Developmental Company 1980C) 1,2,3-trichloropropane was tested for its skin sensitizing properties using the Buehler Test with male and female Dunkin-Hartley guinea pigs in general compliance to OECD TG 406 as at 1980. The test item was tested at the highest non irritating concentration as derived from a pretest (0.5 mL of neat test item) under occlusive conditions for 6 h per exposure (3 induction exposures, 1 challenge exposure). None of the animals in the test group showed a sensitization reaction, while the positive test group (agent: 2,4-dinitro chlorobenzene) showed the sensitivity of the test system. Based on this result 1,2,3-trichloropropane is not a skin sensitizer in this test system and a classification for skin sensitization CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU is not necessary.

5 males and 5 females per group were clipped on the back 48 prior to treatment and finally depilatated with Neet hair remover 24 h prior to treatment. 4 groups were used: a "vehicle" control group (corn oil, even though in the treatment groups the test material was applied undiluted), a positive control group (agent: 2,4-dinitro chlorobenzene) and two test groups - one for sensitization and one for irritation. The irritation group and the "vehicle" control group were not treated with the test item during the induction, while the two other groups were treated with the respective substance on day 2, 9 and 26. Substances were applied to patches which were placed laterally from the midline of the back on the left front quadrant of the exposure areas with the gauze pads adjacent to, but not overlapping, the midline of the backs. On day 30 the two test groups were treated similarly with 1,2,3 -trichloropropane but on a different site, laterally on the right rear quadrant. Positive and negative controls were treated accordingly and all animals were scored for skin reactions 24 and 48 h after challenge exposure using the Draize score system.