Oxydipropanol

Endpoint summary

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other: GLP-compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

EPA OPP 81-6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Justification for non-LLNA method:

Available study pre-dates availability of OECD 429 (LLNA) test guideline.

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Camm Research Lab Animals, Wayne, New Jersey
- Age at study initiation: young adult
- Weight at study initiation: males: 386 to 455 g; females: 355 to 422 g
- Housing: housed individually under standard laboratory conditions in the study room.
- Diet (e.g. ad libitum): Camm Guinea Pig Diet or equivalent
- Water (e.g. ad libitum): potable municipal water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 68-74ºF
- Humidity (%): 35-65%
- Photoperiod (hrs dark / hrs light): 12 hours on/12 hours off cycle

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

Undiluted 0.5 ml

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

Undiluted 0.5 ml

No. of animals per dose:

Test animals: 10 animals; 7 male, 3 female
Control Animals: 5 animals; 3 male, 2 female

Details on study design:

RANGE FINDING TESTS:
To determine the correct concentrations to be used for induction (minimal irritation) and challenge (non-irritating), 5 guinea pigs were exposed to 4 concentrations (10, 25, 50 and 100% w/w in distilled water) of the test material in order to determine (approximately) a highest non-irritating concentration and a concentration that caused minimal irritation. In this screen, both sides of the animal were shaved and sites were exposed to the various concentrations of the material; locations of the concentartions were alternated to avoid site-to-site variations; one test site had normal saline applied.
The substance was tested at 0, 10, 25, 50 and 100% w/w concentration in distilled water. There was no irritation and the 100% concentration of the test substance was seleceted for induction and challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
24 hours before first application of the test substance, and subsquently as necessary, hair was closely clipped on the right side of then animals. A dose of 0.5 ml of the freshly prepared test solution was applied to a non-adherent sterile (aproximately 6 cm2) pad coverd by hypo-allerginec cloth tape. The pad was placed on the shaved surface of the animal, and then further occluded with a latex wrap to ensure adequate contract of the test substance with the skin. The patch remained in place for six hours. At the end of the application period, extremely viscous materials were removed by gentle rinse with warm water. This induction procedure was repeated at the same site during the next 2 weeks for a total of three 6-hour exposures. The interval between induction exposures may vary between 5 and 9 days. The animals were then left untreated for approximately 2 weeks prior to primary challenge. If a second challenge was used, animals were rested for at least one week after the primary challenge.

B. CHALLENGE EXPOSURE
2 weeks after the last induction, the animals and a naive group were challanged at a virgin site (left side) with 0.5 ml at the non-irritating concentration at each site. The test substance was applied as for induction. Reactions were scored at approximately 24, 48 and 72 hours after challenge. If there was more than minimal irritation at the virgin site or if animals were considered to have shown a possible positive reaction they were re-challenged 2 weeks later at an unused site.

Challenge controls:

A group of 5 naive animals were tested for comparison using the challenge concentration - a second naive group was tested for re-challenge if applicable.

Positive control substance(s):

no

Positive control results:

not applicable

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5 ml

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No systemic overt effects were observed and no overt reduced gains in body weight were noted.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No systemic overt effects were observed and no overt reduced gains in body weight were noted. .

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.5 ml

No. with + reactions:

1

Total no. in group:

5

Clinical observations:

No irritation except for transient slight patchy erythema at one site in 1 of the 5 animals.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.5 ml. No with. + reactions: 1.0. Total no. in groups: 5.0. Clinical observations: No irritation except for transient slight patchy erythema at one site in 1 of the 5 animals..

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5 ml

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.5 ml

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

0.5 ml

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

negative control

Dose level:

0.5 ml

No. with + reactions:

0

Total no. in group:

5

Remarks on result:

other: Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: 0.5 ml. No with. + reactions: 0.0. Total no. in groups: 5.0.

Reading:

1st reading

Group:

positive control

Remarks on result:

not measured/tested

Remarks:

No positive control group.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

One Buehler test with guinea pigs (Cosmopolitan Safety Evaluation, Inc., 1995f), performed under GLP and in accordance with EPA OPP 81-6 (Skin Sensitization) guideline, was available for assessment.

A dose of 0.5 ml of the freshly prepared test solution was applied to a shaved surface of 10 animals under occlusion and kept for six hours. This induction procedure was repeated at the same site during the next 2 weeks for a total of three 6-hour exposures, with 5-9 days interval between induction exposures. Two weeks after the last induction, the animals and a naive group were challenged at a virgin site (left side) with 0.5 ml at the non-irritating concentration at each site. The test substance was applied as for induction. Reactions were scored at approximately 24, 48 and 72 hours after challenge.

No irritation was observed except for transient slight patchy erythema at one site in 1 of the 5 animals. Based on these results, dipropylene glycol is considered not to have a skin sensitizing potential.

Also one human study in an eczema population (Johansen et al., 1995) was available for assessment. 503 eczema patients were patch tested with 10% aqueous solution of dipropylene glycol of two different grades (cosmetic and synthesis, purity 96% and 97%, respectively. Patches were applied for 2 days and reactions were scored at days 2, 3 and 5-7. There was only 1 positive patch test to synthesis grade of dipropylene glycol, the remaining reactions being either equivocal (26 in total; 4 patiens having equivocal reactions to both grades of dipropylene glycol) or irritating (7). Overall, the results suggest that dipropylene glycol has a very weak sensitizing potential, if any.

Migrated from Short description of key information:
Based on the result of the GLP-compliant Buehler test with guinea pigs, dipropylene glycol is not sensitising to skin.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No data on respiratory sensitization are available. However, in accordance with Section 1 of REACH Annex XI, the study is scientifically unjustified, as respiratory tract sensitization is not expected based on the fact that dipropylene glycol is not skin sensitizer and no human data are available indicating a concern for respiratory sensitization.

Justification for classification or non-classification

Based on the absence of skin sensitizing effect in a Buehler study with guinea pigs and the lack of data indicating the respiratory sensitization of dipropylene glycol, classification according to Directive 67/548/EEC and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 is not warranted.