•Theaspirane; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, read-across, and/or ...TTC.
•Butanoic acid, 2-methyl-5-(1-methylethyl)cyclopentyl ester; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were ...cleared using target data, read-across, and/or TTC.
•Benzenepropanol, α, γ, γ-trimethyl-; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target ...data, read-across, and/or TTC.
•Ethyl pyruvate; a safety assessment based on RIFM’s criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, read-across, ...and/or TTC.
•Cyclohexanol, 5-methyl-2-(1-methylethyl)-, acetate, (1a,2a,5b)-; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints ...were cleared using target data, read-across, and/or TTC.
•MATERIAL NAME; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, read-across, ...and/or TTC.
•2,6-Dimethyl-10-methylene-2,6,11-dodecatrienal; a safety assessment based on RIFM's criteria.•A safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared ...using target data, read-across, and/or TTC.
•p-Mentha-1,8-dien-7-ol, safety assessment based on RIFM's criteria.•Safety assessment based on 7 human health endpoints plus environmental.•All endpoints were cleared using target data, read-across, ...and/or TTC.
Background. Perfumes are complex mixtures composed of many fragrance ingredients, many of which are known to be only weak allergens when tested individually. It is therefore surprising that fragrance ...contact allergy is one of the most common forms of contact allergy.
Objectives. To investigate whether mixing different fragrance allergens leads to increased sensitization potency, and to examine the difference in the challenge response to one chemical in mice sensitized either with the mixture of allergens or with only the relevant allergen.
Methods. CBA mice were sensitized with three different concentrations of three fragrance allergens alone or as a mixture. The sensitization and elicitation responses were measured by ear thickness plus infiltration of B and T cells and T cell proliferation in the draining lymph nodes.
Results. We found a dose‐dependent sensitization response for each of the allergens. An increased response was seen when the allergens were mixed. A stronger challenge response to cinnamal was seen in mice sensitized with the allergen mixture than in mice sensitized with cinnamal alone.
Conclusions. Our findings suggest that mixtures of allergens increase the primary response that potentiates the generation of memory T cells in response to the specific allergen. Thus, allergen mixtures enhance both induction and elicitation of contact allergy.
Several aromatic aldehydes such as 3-(4-tert-butylphenyl)-2-methylpropanal were shown to adversely affect the reproductive system in male rats following oral gavage dose of ≥ 25 mg/kg bw/d. It was ...hypothesized that these aldehydes are metabolized to benzoic acids such as p-tert-butylbenzoic acid as key toxic principle and that Coenzyme A (CoA) conjugates may be formed from such acids. Here we performed a detailed structure activity relationship study on the formation of benzoic acids from p-alkyl-phenylpropanals and related chemicals in rat hepatocytes in suspension. Formation of CoA conjugates from either p-alkyl-phenylpropanals directly or from their benzoic acid metabolites was further assessed in plated rat hepatocytes using high resolution LC-MS. All of the test chemicals causing reproductive adverse effects in male rats formed p-alkyl-benzoic acids in rat hepatocytes in suspension. Compounds metabolized to p-alkyl-benzoic acids led to accumulation of p-alkyl-benzoyl-CoA conjugates at high and steady levels in plated rat hepatocytes, whereas CoA conjugates of most other xenobiotic acids were only transiently detected in this in vitro system. The correlation between this metabolic fate and the toxic outcome may indicate that accumulation of the alkyl-benzoyl-CoA conjugates in testicular cells could impair male reproduction by adversely affecting CoA-dependent processes required for spermatogenesis. This hypothesis prompted a search for new p-alkyl-phenylpropanal derivatives which do not form benzoic acid metabolites and the corresponding CoA conjugates. It was found that such metabolism did not occur with a derivative containing an o-methyl substituent, ie, 3-(4-isobutyl-2-methylphenyl)propanal. This congener preserved the fragrance quality but lacked the male reproductive toxicity in a 28-day rat study, as predicted from its in vitro metabolism.
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