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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:
March 22 - April 25 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
- reduced numbers of animals used (10 rather than 20 in test group), no control animals
Principles of method if other than guideline:
Ten male guinea pigs, weighing 300-400 g were used to assess the contact dermal irritation/sensitisation potential of Tris (2-ethylhexyl)trimellitate/Nuoplaz 6959/TOTM. The animals were housed & maintained in compliance with the animal welfare act (Pub. L-94-279) 9CFR part 3. ). TOTM was applied to intact skin sites and left in contact for 24h. TOTM was applied a second time on the same sites on day 3 and the sequence was repeated for a total of 10 applications. The animals were untreated for 2 weeks after which a challenge dose was applied to new skin sites for 24h . Twenty -four h after each application in the induction phase and 24 & 48h after the challenge application the sites were examined for signs of irritation and any findings scored using the Draize method.
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Study undertaken prior to the introduction of the LLNA (OECD TG 429 originally adopted April 2002)
Species:
guinea pig
Strain:
other: albino
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: Not reported
- Weight at study initiation: 300-400 g
- Housing: Stainless steel cages with elevated wire mesh flooring
- Diet (e.g. ad libitum): ad libitum, Charles River Guinea pig Formula,
- Water (e.g. ad libitum): ad libitum, tap water
- Acclimation period: No data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 70 +/-2 degrees F
- Humidity (%): 45+/-5
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12:12
IN-LIFE DATES: From: 21 September To: 28 October 1981
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Induction phase: neat Tris (2-ethylhexyl)trimellitate/Nuoplaz 6959/TOTM
Challenge phase: Tris (2-ethylhexyl)trimellitate/Nuoplaz 6959/TOTM
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
Induction phase: neat Tris (2-ethylhexyl)trimellitate/Nuoplaz 6959/TOTM
Challenge phase: Tris (2-ethylhexyl)trimellitate/Nuoplaz 6959/TOTM
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS: No data

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: 24 h
- Test groups: 1
- Control group: 0 (none)
- Site: Not specified
- Frequency of applications: 10 with a 24h recovery period between them
- Duration: Until Tris (2-ethylhexyl)trimellitate/Nuoplaz 6959/TOTM had been applied 10 times
- Concentrations: 0.5 ml of 100%/neat TOTM

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 2 weeks after 10th sensitising/induction application
- Exposure period: 24 h
- Test groups: 1
- Control group: 0 (none)
- Site: No data
- Concentrations: 100%, used as supplied
- Evaluation (hr after challenge): 24 & 48h

OTHER:
Challenge controls:
None used
Positive control substance(s):
no
Positive control results:
None no positive control group on study
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100% TOTM
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No data
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% TOTM. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No data.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100% TOTM
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No data
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% TOTM. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No data.
Group:
negative control
Remarks on result:
not measured/tested
Group:
positive control
Remarks on result:
not measured/tested

Induction score : 0.0

Topical challenge scores

after 24 h:0.0

After 48h :0.0

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this test is not a primary irritant, fatiguing agent or skin sensitiser in the albino guinea pig. No skin reactions were seen during the induction (sensitising) phase or subsequent challenge phase.
Executive summary:

Delayed dermal sensitisation has been assessed using the Buehler method.

No sensitisation response was reported at challenge following a period of induction exposures to the substance

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

Delayed dermal sensitisation has been assessed in the guinea pig using the Buehler method. No sensitisation response was reported at challenge following a period of induction exposures to the substance.

In addition, the potential sensitizing effects of a number of plasticizers, including TOTM, has been examined in a human repeated insult patch test. The substances were judjed to be non-sensitizers based on the criteria established by the FDA for sensitization of human subjects


Migrated from Short description of key information:
Skin sensitisation: Not sensitising

Justification for selection of skin sensitisation endpoint:
Best documented of the available studies

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

No sensitisation response was reported at challenge following a period of induction exposures to the substance in both animal and human models.