Acute toxicity testing of chemicals-Opportunities to avoid redundant testing and use alternative approaches.

Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin and eye irritancy, and skin sensitisation potential of chemicals is required under regulatory schemes worldwide. In vivo studies conducted to assess these endpoints can sometimes be associated with substantial adverse effects in the test animals, and their use should always be scientifically justified. It has been argued that while information obtained from such acute tests provides data needed to meet classification and labelling regulations, it is of limited value for hazard and risk assessments. Inconsistent application of in vitro replacements, protocol requirements across regions, and bridging principles also contribute to unnecessary and redundant animal testing. Assessment of data from acute oral and dermal toxicity testing demonstrates that acute dermal testing rarely provides value for hazard assessment purposes when an acute oral study has been conducted. Options to waive requirements for acute oral and inhalation toxicity testing should be employed to avoid unnecessary in vivo studies. In vitro irritation models should receive wider adoption and be used to meet regulatory needs. Global requirements for sensitisation testing need continued harmonisation for both substance and mixture assessments. This paper highlights where alternative approaches or elimination of tests can reduce and refine animal use for acute toxicity requirements.

Studies to investigate the absorption and excretion of shea oleine sterols in rat and man.

Shea oleine (SU), an oil fraction derived from the nut of the African tree, Butyrospermum parkii, is used as a frying oil and, after hardening (SH), in margarine and toffee fat. Both SU and SH contain a high level (approximately 8%) of 4,4-dimethylsterols (4,4-DMS), mostly as esters of cinnamic acid. As part of a series of studies evaluating SU, investigations to study rat and human dietary utilization were carried out. These comprised fecal fat analysis of groups of Wistar rats and a small number (four subjects) of human volunteers. Groups of rats were administered SU in a semisynthetic diet over 3 weeks at up to 20% in the diet (approximately 10 g/kg/day). In the human study, four male volunteers consumed a single 25-g portion of SU (approximately 0.4 g/kg) and ate no other vegetable fat during the course of the study. No preferential absorption of any of the 4,4-DMS occurred in the rat or man. Apparent absorption of the most prominent sterol fraction in the unsaponifiable material, 4,4-DMS, as estimated by its disappearance from feces, was similar in both species (27% to 52% in the rat compared with 13% to 49% in human subjects). Both rats and humans showed a similar profile of dietary and fecal 4,4-DMS fraction sterol components.

A 13-week feeding study in the rat with shea oleine and hardened shea oleine.

Shea oleine is an oil fraction derived from the nut of the tree, Butyrospermum parkii, which grows in central and western Africa. There are several uses of shea oleine, including its use as a cooking oil and, after hardening, in margarine and toffee fat. As part of a series of studies, a 13-week rat feeding study was conducted in which groups of Colworth-Wistar rats (15 male and 15 female) were fed 27.5% total fat semipurified diets containing 20% (w/w) shea oleine (SU) or hardened shea oleine (SH). Equivalent groups of rats were fed either 20% (w/w) palm oil (PU), soyabean oil (BU), or the hardened (hydrogenated) equivalents (PH and BH, respectively). Assessments of body weight, food and water intake, clinical pathology, organ weights, and macroscopic histopathology were carried out. Results showed that shea oleine diets produced similar biological effects to palm oil and and soyabean oil diets. A slightly reduced body weight gain was noted in rats fed either of the shea oleine diets in comparison with palm oil and soyabean oil. The process of hardening had no significant impact on the normal growth in rats fed shea oleine, although minor differences compared with unhardened diets comprised some small changes in clinical chemistry parameters, raised liver weight, and less liver lipid. In addition, raised alkaline phosphatase and an increase in food intake were noted in rats fed SH. All diets were well tolerated in the growing rat and none of the findings in the study were considered to be adverse.