Registration Dossier

Administrative data

Description of key information

not sensitising, (OECD TG 406, guinea pig maximisation test); study Shell Development Company (1980C) / key (Hartley-Albino guinea pigs, Buehler Test, OECD TG 406)

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
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
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Buehler Test
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.
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
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
details not given in the SIDS report study summary
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
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)
Positive control results:
Sensitivity of the guinea pigs to the experimental procedure was confirmed with known human sensitizers: DNCB (2,4-dinitro chlorobenzene).
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
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
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.

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

- The classification of the key parameter is based on results of the study Shell Development Company (1980C) / key (Hartley-Albino guinea pigs, Buehler Test, OECD TG 406) considered to be fully reliable and compliant to OECD TG 406 by the SIDS INITIAL ASSESSMENT REPORT For SIAM 18 - 1,2,3-Trichloropropane as at 2004. Shell Development Company (1980C) / key (Hartley-Albino guinea pigs, Buehler Test, OECD TG 406). In an additional study that is only available from a secondary source this finding is confirmed (guinea pig maximisation test; Bio/dynamics Inc. (1985), Buehler test). In Clark (1977, guinea pig maximisation test) slight positive results were found. Nevertheless these effects would not be sufficient for classification. Anyway the study is regarded unreliable as the study was conducted with 1,2,3 -trichloropropane of a purity of 92 % without any information on the nature of the impurities.
Therefore 1,2,3 -trichloropropane is deemed not to be a skin sensitizer which is in-line with the current classification and labelling.



Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

- No information on the sensitising potential of 1,2,3-trichloropropane via the inhalation route is available. As 1,2,3-trichloropropane is not a sensitizer via the dermal route the risk that the substance is a respiratory sensitizer is regarded negligible.


Justification for classification or non-classification

- Based on the results presented above, 1,2,3 -chloropropane is not a skin sensitizer and therefore does not need to be classified for skin sensitization according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).

- No information on the sensitising potential of1,2,3 -chloropropane via the inhalation route is available. As 3-chloropropene is not a sensitizer via the dermal route the risk that 3-chloropropene is a respiratory sensitizer is regarded negligible. Based on this reasoning 3 -chloropropene does not need to be classified for respiratory sensitization according to CLP as implementation of UN GHS in the EU (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL).