3 ketone solvents (methyl ethyl ketone (MEK), methyl isobutyl ketone (MiBK), and isophorone) were tested for potential genotoxicity. The assays of MEK and MiBK included the Salmonella/microsome (Ames) assay, L5178Y/TK+/- mouse lymphoma (ML) assay, BALB/3T3 cell transformation (CT) assay, unscheduled DNA synthesis (UDS) assay, and micronucleus (MN) assay. Only the ML, UDS, and MN assays were conducted on samples of isophorone. No genotoxicity was found for MEK or isophorone. The presence of a marginal response only at the highest, cytotoxic concentration tested in the ML assay, the lack of reproducibility in the CT assay, and clearly negative results in the Ames assay, UDS and MN assays, suggest that MiBK is unlikely to be genotoxic in mammalian systems.

Animals↗

PubMed1987

A 14-week vapor inhalation toxicity study of methyl isobutyl ketone.

In a 2-week probe study male and female Fischer-344 rats and B6C3F1 mice were exposed 6 hr/day to 2000, 500, 100, or 0 ppm methyl isobutyl ketone (MIBK). At 2000 ppm there was a slight increase in male rat liver weight (absolute and relative). The only changes observed histologically were increases in regenerative tubular epithelia and hyalin droplets in kidneys of male rats exposed to 2000 or 500 ppm. Exposure levels for a subchronic study were 0, 50, 250, or 1000 ppm methyl isobutyl ketone vapors 6 hr/day, 5 days per week, for 14 weeks. The 14 weeks of exposure had no adverse effect on the clinical health or growth of rats or mice. Male rats and male mice exposed to 1000 ppm MIBK had a slight but statistically significant increase in liver weight and the liver weight/body weight ratio. Liver weight was also increased slightly in male mice exposed to 250 ppm. No gross or microscopic hepatic lesions related to MIBK exposure were observed. Furthermore, the only microscopic change observed was an increase in the incidence and extent of hyalin droplets within proximal tubular cells of the kidneys of male rats exposed to 250 and 1000 ppm of MIBK. The relevance of the male rat kidney tubular effect to humans is not known. In conclusion, other than the male rat kidney effect, exposure of male and female rats and mice to MIBK at levels up to 1000 ppm for 14 weeks was without significant toxicological effect.

Administration, Inhalation↗

PubMed1987

Developmental toxicity evaluation of inhaled methyl isobutyl ketone in Fischer 344 rats and CD-1 mice.

Pregnant Fischer 344 rats and CD-1 mice were exposed to methyl isobutyl ketone vapor (CAS No. 108-10-1) by inhalation on Gestational Days 6 through 15 at concentrations of 0, 300, 1000, or 3000 ppm (mean analytical values of 0, 305, 1012, and 2997 ppm, respectively). The animals were sacrificed on Gestational Day 21 (rats) or 18 (mice), and live fetuses were examined for external, visceral, and skeletal alterations. In rats, exposure to 3000 ppm resulted in maternal toxicity expressed as clinical signs, decreased body weight and body weight gain, increased relative kidney weight, and decreased food consumption, and in fetotoxicity expressed as reduced fetal body weight per litter and reductions in skeletal ossification. In mice, exposure to 3000 ppm resulted in maternal toxicity expressed as exposure-related increases in deaths (12.0%, 3/25 dams), clinical signs, and increased absolute and relative liver weight, and in fetotoxicity expressed as increased incidence of dead fetuses, reduced fetal body weight per litter, and reductions in skeletal ossification. No treatment-related increases in embryotoxicity or fetal malformations were seen in either species at any exposure concentration tested. There was no evidence of treatment-related maternal, embryo, or fetal toxicity (including malformations) at 1000 or 300 ppm in either species.

Administration, Inhalation↗

PubMed1987

Peroxisome induction studies on seven phthalate esters.

Seven phthalate esters, representing a variety of chain lengths and degrees of branching in the alcohol moiety, were tested for their ability to produce peroxisome proliferation in the Fischer 344 rat. Di(2-ethylhexyl)adipate (DEHA) was tested using the same protocol and di(2-ethylhexyl)phthalate (DEHP) was run with each study as an internal control. Each ester was administered in the feed for a period of 21 days at levels of 2.5%, 1.2% and either 0.6% or 0.3%. DEHP and DEHA were also fed at levels of 0.1% and 0.01%. The animals were sacrificed and samples of liver were prepared for both light and electron microscopy. Serum samples were assayed for both triglyceride and cholesterol. The remaining portion of the liver was homogenized and assayed for cyanide-insensitive palmitoyl-CoA oxidation, lauric acid 11-hydroxylase and lauric acid 12-hydroxylase. The results show that there is approximately a ten-fold difference between the weakest and strongest esters in terms of their potency to induce changes in relative liver weight and in several of the biochemical parameters. In general, the longer chain esters were more potent than the shorter chain ones, and branched chain esters seemed more potent than straight. Several statistical analyses of the dataset have been performed and all render similar conclusions. The results of one of these evaluations are presented elsewhere in this volume (Lin, 1987).

Animals↗

PubMed1980

Acute oral toxicity of selected flavor chemicals.

The acute oral lethal doses are reported in rats or mice for 63 substances which are used in flavorings. For specific groups of compounds which contain several representatives of one structural class, some effects of structure on acute oral toxicity were observed. For pyrazines, the addition and position of methyl groups affected the toxicity while the substitution of ethyl for methyl had little effect. Toxicity increased with the proximity of the methyl group. The thiazoles and thiazolines tested had similar toxicities regardless of the side groups. The furan thioesters tested were about equally toxic, a fact which would be consistent with hydrolysis to the acid plus thiol.

Animals↗

PubMed1980

Toxicology advisory guidelines for fragrance safety assurance.

Explore the source record for details and available documents.

Dermatitis, Contact↗