1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylindeno[5,6-c]pyran

Endpoint summary

Description of key information

Skin sensitisation: no skin sensitiser based on testing in OECD TG 406.

Respiratory sensitisation: the substance is not considered a respiratory sensitiser in absence of human data and in absence of skin sensitisation from animal/in vitro tests.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Key study Skin Sensitisation

The sensitising potential of Galaxolide (65% HHCB in DEP) was tested in a guinea pig maximization test (OECD TG 406, non-GLP). The used doses of Galaxolide were 0.5% in 0.01% dodecylbenzene sulphonate in 0.9% saline (DOBS/saline) for the intradermal injection, 100% for the induction patch, and 25% in 70% acetone/30% polyethylene glycol 400 (acetone/PEG400) for the challenge patch. These doses were selected based on preliminary irritation tests using 0.1, 0.25, 0.5, 1.0 and 2.0% Galaxolide concentrations for intradermal injections, however the selection criteria were not clear. The actual concentrations of HHCB are 0.325%, 65%, and 16.25%, respectively. Ten (six male, four female) Albino Dunkin/Hartley guinea pigs (weight 316-350g) were tested on a 2cm x 4cm area of skin in the dorsal shoulder area, clipped and shaved free of fur. Induction consisted of a 0.1 ml intradermal injection of 0.325% HHCB in DOBS/saline and 0.1 ml 50% Freund’s Complete Adjuvant in 0.9% saline. This was followed one week later by a 48-hr occluded patch saturated with 65% HHCB. Challenge applications were made 14 days later with a patch with 16.25% HHCB in 70% acetone/30% PEG 400. Two repeat challenges at weekly intervals were conducted. Observations were made after each challenge at 24 and 48 hours. Eight control animals were received induction and challenge treatments similar to the test pigs minus the test material. At challenge 1, in one animal very faint to faint erythema (score 0.5-1) was noted at 24 hours. In all three challenges three or less per group of ten animals showed very faint erythema (score 0.5) at 24 or 48 hours. There was no evidence of sensitisation in any of the guinea pigs at any of the three challenge treatments.

Other Supporting studies (EU-RAR, 2008)

Galaxolide (65% HHCB in DEP) was tested (OECD 406, in compliance with GLP, K2) for its allergenic and photo-allergenic potential in 12 albino Hartley strain guinea pigs (418 to 487 g) with Freund's adjuvant injection. Dermal induction (1% Galaxolide (65% HHCB in DEP)) was performed twice (second induction after 24hr), once including adjuvant injections, one excluding adjuvant injections. After 25 min, the sites were exposed to ultraviolet light. A control group was included. Ten to fourteen days after induction, a challenge with 1, 0.3 or 0.1% Galaxolide in ethanol (actual HHCB concentrations 0.65%, 0.2%, and 0.065%) was performed by dermal application. Thirty min later, the animals were irradiated as above, after which the test material was applied to fresh sites to check for contact sensitivity, and the sites scored at 24 and 48 hr. A second challenge was carried out 6 or 7 days later. In 1/12 a very faint trace of erythema was found at 1.0% and 0.3% Galaxolide with UVA at challenge 1 and 2. Under the conditions of the study, Galaxolide is not a photosensitiser in guinea pigs. (Parish, 1988)

 

In a skin sensitisation experiment with guinea pigs, 0,1% Galaxolide in physiological saline was injected intracutaneously (first injection 0.05 mL followed by 9 injections of 0.1 mL). Two weeks after induction, for the challenge 0.05 mL 0.1% was injected. After a 24-hour observation period, no signs of sensitisation were observed (Levenstein, 1963).

Additionally, several human studies are available, which have been summarized in the table below (source: EU-RAR, 2008).

 

Study Type	Number tested	Concentration of HHCB	Patch details	Result	Reference
HRIPT	40	3.75% Galaxolide in alcohol	Semi-occlusive, 9 applications of 24-Hr each	Negative	Rubenkoenig and Ede, 1964
HRIPT	43	100% 50% Galaxolide in alcohol SDA 39Cl	Semi-occlusive, 8-9 applications of 24-Hr each	Negative	Guillaume et al., 1973a
HRIPT	42	100% neat HHCB, no vehicle	Semi-occlusive, 8-9 applications of 24-Hr each	Negative	Guillaume et al., 1973b
Maximization	10	65% HHCB in DEP, vehicle-petrolatum	Occlusive, 48-hr patch on 5 alternate days.	Negative	Epstein, 1974
Maximization	24	65% HHCB in DEP, vehicle-petrolatum	Occlusive, 48-hr patch on 5 alternate days.	Negative	Epstein, 1979

The available data with guinea pigs and humans (HRIPT and maximization tests) provide no evidence of potential for induction of sensitisation for HHCB. There is no evidence from studies in experimental animals or with humans, that HHCB is a photosensitiser.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Respiratory sensitisation can be assessed using human data such as indicated in R7.3.5.2 of the ECHA guidance (2015) that indicate respiratory reactions e. g. from consumer experience or occupational exposure. In case no such data are available the respiratory sensitisation can be assessed using the integrated evaluation strategy for respiratory sensitisation data in the ECHA guidance (R7A, Fig. 7.3-4, 2017), which says that if the substance is not a skin sensitiser, it is unlikely to be a respiratory sensitiser.

Justification for classification or non-classification

Based on the available skin sensitisation studies, test item does not have to be classified for skin sensitisation in accordance with EU CLP (1272/2008 and its amendments.