Glycerides, castor-oil mono-, di- and tri-

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames test (OECD 471): negative

HPRT assay (OECD 476): negative

The clastogenic potential of a structurally related substance was assessed in a chromosomal aberration (similar to OECD 473) assay and a sister chromatid exchange assay (similar to OECD 479): both negative.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

For the substance itself, an Ames test and HPRT assay are available. Data on cytogenicity are derived from the structural analogue CAS 8001-79-4.

Ames test (OECD 471)

An Ames test, similar to OECD guideline 471 and GLP principles, was used to determine the mutagenicity of the test item in bacterial cells. The test item was tested on S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100, in absence and presence of Aroclor 1254 induced rat S9 -mix as metabolic system. Test concentrations were between 8 to 5000 µg/plate were applied according to the plate incorporation method. No cytotoxicity was observed up to the guidelines recommended maximum test concentration. Positive controls and a vehicle and negative (untreated cells) control were taken along.  The substance did not induce any reverse mutations in the absence or presence of S9 -mix. Therefore, it is concluded that the substance is not mutagenic under the conditions of the test (Henkel, 1990).

HPRT assay (OECD476)

In a HPRT assay conducted according to OECD guideline 476 and GLP, Chinese hamster lung fibroblasts (V79) cells cultured in vitro were exposed to the test substance. Two pre-experiments were performed in order to determine the toxicity of the test item at incubation times of 4 (+/- metabolic activation) and 24 hours (- metabolic activation) up to a concentration of 2 mg/mL. Based on observed cytotoxicity and phase-separation, the main experiment I (4 hour incubations in absence and presence of Phenobarbital/ß-naphthoflavone induced rat liver S9) was performed in duplicate with the following concentrations: 2.3, 4.7, 9.4, 18.8, 37.5, 75.0, 150.0 and 300 µg/ mL. Based on these additional observation, in experiment II, with an incubation time of 24 hours in absence of S9 and 4 hours in presence of S9 the following concentrations were used: 2.3, 4.7, 9.4, 18.8, 37.5, 75.0 and 150.0 µg/ mL. In experiment IIA the 24 hour incubations in absence of S9 were repeated under the same conditions. Phase separation was observed at doses of 37.5 µg/mL and above. To avoid analysis of too many phase separating concentrations the highest three (experiment I) or two (experiment II and IIA) concentrations were excluded from analysis. When sufficient analysable concentrations were available, the lowest concentration was excluded as well. Concurrent vehicle (DMSO) and positive controls were included and these results were in the historical ranges. No cytotoxicity (determined as cloning efficiencies) was observed at the analysed substance concentrations. In addition, no relevant and reproducible increase in mutant colony numbers/10^6 cells was observed in the main experiments up to the maximum concentration. Therefore, under the test conditions, the test substance is non-mutagenic in the HPRT mammalian cell mutation assay (Envigo, 2017).

Chromosomal aberration assay (NTP) with CAS 8001-79-4

A chromosome aberration test, similar to OECD guideline 473 and according to NTP standards, was conducted to determine the clastogenicity of the test item in mammalian cells. The test item was supplemented at dose levels of 1600, 3000 and 5000 µg/ plate in presence (2 hour incubation time) and absence (10 hour incubation time) of Aroclor 1254-induced rat S9 as metabolic system. Solvent and positive controls were included and showed that the test system was sensitive to detect the induction of structural aberrations potential. After Giemsa staining, two hundred first-division metaphase cells were scored at each dose level (50 for the high dose positive control). The substance did not induce chromosomal aberrations, both in the absence or presence of the bioactivation systems. Therefore, it is concluded that the substance is not clastogenic under the conditions of the test (NTP, 1987).

Sister Chromatid Exchange assay (NTP) with CAS 8001-79-4

A Sister Chromatid Exchange assay, similar to OECD guideline 479 and according to NTP standards, was conducted. The test item was supplemented at dose levels of 160, 500 1600 and 5000 µg/ plate in presence (2 hours incubation) and absence (2 hour incubation) of Aroclor 1254-induced rat S9 as metabolic system. Solvent and positive controls were included and showed that the test system was sensitive to detect DNA damage. After staining, fifty second-division metaphase cells were scored to determine the frequency of SCE/cell for each dose level (10 cells for the high dose positive control).The substance did not induce chromosomal aberrations, both in the absence or presence of the bioactivation systems. Therefore, it is concluded that the substance is not clastogenic under the conditions of the test (NTP, 1986).

Ames test (NTP) with CAS 8001-79-4

An Ames test, similar to OECD 471 and according to NTP standards, was conducted to determine the mutagenicity of the test item in bacterial cells. The substance was tested on S. typhimurium TA 100, TA 1535, TA 97 and TA 98 in absence and presence induced rat and hamster S9 as metabolic system (both at 10 and 30%). The substance was applied at concentrations of 0, 100, 333, 1000, 3333 and 10000 µg/plate using DMSO as vehicle. Solvent and positive controls were included and showed that the test system was sensitive to detect mutagenic potential. The substance did not induce any reverse mutations in the absence or presence of the bioactivation systems. Therefore, it is concluded that the substance is not mutagenic under the conditions of the test (NTP, 1983).

Justification for classification or non-classification

The substance was not mutagenic in the Ames and HPRT assays and a structurally related substance did not show clastogenic potential. Therefore, classification for genetic toxicity is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.