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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:
1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline 406
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The study was performed prior to the implementation of REACH and therefore pre-dates the requirement to use the LLNA as the method of choice for assessing skin sensitising potential.
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, FRG.
- Age at study initiation: 2 months old
- Weight at study initiation: 355 to 432 g
- Housing: The animals were housed in metal cages with wire-mesh floors
- Diet (e.g. ad libitum): Standard guinea pig diet, including ascorbic acid (1600 mg/kg) ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: A combined quarantine/acclimation period of 13 days was observed (7 days for the primary irritation animals).


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21°C
- Humidity (%): 35-75%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: From: October 25, 1988 (Primary irritation test) To: December 1, 1988 (Buehler study)
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
Undiluted test compound (0.5% w/w)
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
Undiluted test compound (0.5% w/w)
No. of animals per dose:
20 test animals and 10 control animals
Details on study design:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Nine repeated occluded topical applications
- Exposure period: 6 hours
- Site: Scapula region (left side)
- Frequency of applications: Nine times during the first three weeks (days 0, 2, 4, 7, 9, 11, 14, 16, 18)
- Concentrations: Undiluted


B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: one (day 28)
- Exposure period: 6 hours
- Site: Clipped and shaved right flank
- Concentrations: undiluted (0.5% w/w)
- Evaluation (hr after challenge): 24 and 48 hours after removal of the dressings


OTHER: The primary irritation experiments included a treatment of one animal with the undiluted test substance (mainly to assess any toxic effects) and epicutaneous application with four guinea pigs of several concentrations of the test substance: 100%, 50%, 25% and 10% (w/w), in propylene glycol to assess primary irritancy. The left flank of the first animal was exposed to 0.5 ml of the test substance for 24 hours. This treatment caused no skin irritation. The left flank of ther four other animals was exposed to 0.05 ml of each of the above mentioned concentrations for 6 hours. No signs of systemic toxicity were observed in any of the five treated animals.
Positive control substance(s):
yes
Positive control substance(s):
other: formaldehyde solution
Positive control results:
A sensitization rate of 50% was obtained to the 1% concentration.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
undiluted
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: undiluted. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

The challenge treatment resulted in no skin reactions in any of the experimental animals or the controls. No signs of systemic toxicity were observed in any of the animals during the study. Thus, a sensitization rate of 0 % was obtained.

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Applying the EEC criteria for classification and labelling of dangerous substances, DOWANOL TPnB need not be labelled as sensitizing to skin.
Classification: not sensitizing
Executive summary:

A sample of Dowanol TPnB (batch no. 880621 R004) with a purity of 98.47% was evaluated by the Buehler test to determine its sensitizing potential. The test guidelines followed were in conformity with OECD 406 and EU B.6.

Thirty-five young adult female guinea pigs of the Dunkin-Hartley strain, SPF quality, approximately 2 months old and weighing 355 to 432 g at the start of the experiment were used. The animals were housed in metal cages with wire mesh floors. They were fed standard guinea pig diet, including ascorbic acid (1600 mg/kg) and had free access to tap water.

The animal room temperature was maintained between 19 and 21ºC and the relative humidity between 35 and 75 per cent. The artificial light sequence was 12 hours light and 12 hours dark.

The primary irritation experiments included a treatment of one animal with the undiluted test substance (mainly to assess any toxic effects) and epicutaneous application with four guinea pigs of several concentrations of the test substance: 100%, 50%, 25% and 10% (w/w), in propylene glycol to assess primary irritancy. The left flank of the first animal was exposed to 0.5 ml of the test substance for 24 hours. This treatment caused no skin irritation. The left flank of the four other animals was exposed to 0.05 ml of each of the above mentioned concentrations for 6 hours. No signs of systemic toxicity were observed in any of the five treated animals.

The experimental group consisted of 20 animals and 10 animals were used as a control group. The animals were subjected to nine epicutaneous occlusive induction exposures with the undiluted test compound. The control animals were treated with a dry patch. Ten days after the last induction treatment, all animals were challenged with the undiluted test substance and a dry patch. The challenge treatment resulted in no skin reactions in any of the experimental animals and the control animals as well. No signs of systemic toxicity were observed in any of the animals during the study.

Thus, a sensitization rate of 0% was obtained.

Applying the EEC criteria for classification and labeling of dangerous substances, the test substance need not be labeled as sensitizing to skin.

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

Tripropylene glycol butyl ether (TPnB) was tested undiluted in guinea pigs for skin sensitization potential. At both readings (24- and 48-hours after challenge), all scores in treated animals were 0 for erythema or edema, and remained 0 at the 48-hour reading.


Migrated from Short description of key information:
A GLP-study according to OECD guideline 406 (Buehler method) is available for tripropylene glycol butyl ether.

Justification for selection of skin sensitisation endpoint:
GLP study conducted according to OECD TG 406

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No studies on respiratory sensitization is available for triptopylene glycol n-butyl ether but an assessment of respiratory sensitization potential is made using the skin sensitization and genotoxicity data. Based on the absence of skin sensitising potential, genotoxicity and irritancy, tripropylene glycol n-butyl ether is not expected to be a respiratory tract sensitizer.


Migrated from Short description of key information:
No studies on respiratory sensitization is available for triptopylene glycol n-butyl ether but an assessment of respiratory sensitization potential is made using the skin sensitization and genotoxicity data.

Justification for classification or non-classification

In the sole skin sensitization study in guinea pigs, at both readings (24- and 48-hours after challenge), all scores in treated animals were 0 for erythema or edema, and remained 0 at the 48-hour reading. Based on the results and EU classification and labeling criteria as laid down in Annex VI of the EEC Council Directive 67/548 EEC (amended by Directive 83/467 EEC) and in accordance with CLP (Guidance to Regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, tripropylene glycol n-butyl ether (TPnB) is not a contact sensitizer. Based on the absence of skin sensitising potential, genotoxicity and irrtancy, tripropylene glycol n-butyl ether (TPnB) is not expected to be a respiratory tract sensitizer.