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Key value for chemical safety assessment

Effects on fertility

Additional information

The reproductive toxicity of high flash aromatic naphtha (C9 aromatics) was examined in a three generation study in which 30 rats of each sex (F0 generation) were exposed via inhalation to 100, 500, or 1500 ppm for 6 hrs/day, 5 days/week for 10 weeks prior to mating until GD20. This exposure regime was repeated for two subsequent generations. The results show no exposure related effects to fertility in either male or female rats. The NOAEL (inhalation) for reproductive toxicity for the P, F1, and F2 generation was >=1500 ppm.

Short description of key information:
Hydrocarbons, C9, aromatics, were examined for toxicity in a three-generation reproductive toxicity study. The NOAEL (inhalation) for reproductive toxicity for the P, F1, and F2 generation was >=1500 ppm.

Effects on developmental toxicity

Description of key information
Maternal (inhalation) NOAEL = 100 ppm
Developmental (inhalation) NOAEL = 100 ppm
Additional information

A study was conducted to determine the developmental toxicity of C9 aromatics in mice. Groups of 30 pregnant female mice were exposed via inhalation to 100, 500, or 1500 ppm for 6 hrs per day during gestation days 6 -15. The mice were sacrificed on gestation day 18, and examined for a variety of fetal developmental parameters including number of viable and nonviable fetuses, number of resorptions, total implantations, and number of corpea lutea. Animals were also examined for maternal toxicity signs including body weight, and changes in appearance and behaviour. There was a statistically significant reduction in body weight gain in dams and reduced mean body weight for fetuses in the 500 ppm exposure group, and therefore the LOAEC is 500 ppm for both maternal and developmental toxicity. There was no reduction in mean body weight or any other exposure related adverse effects for fetuses in the 100 ppm exposure group. Therefore, the maternal and developmental toxicity NOAEC = 100 ppm. The maternal toxicity LOAEC was 500 ppm based on significant reduction in weight gain for the dams. The development toxicity LOAEC was 500 ppm based on significant reduction in weight gain likely caused by the significant reduction in maternal body weight.

The developmental toxicity of cumene (isopropyl benzene) was evaluated in Sprague-Dawley rats exposed to 0, 100, 500 or 1200 ppm 6 hours/day on gestation days 6-15 (Darmer et al., 1997). Mean body weight gain was statistically significantly decreased in the 1200 ppm dams on gestation days 6-9 and 6-15, although no significant differences in maternal body weight were observed in any of the treated groups compared to control rats. However, there were no treatment-related observations at gross necropsy, maternal corrected gestational weight change or gravid uterine weight differences. With regard to the fetus, there were no differences in the incidences of malformations or other gestational parameters including number of corpora lutea, number of nonviable (early or late resorptions or dead fetuses), viable implantations, percent pre- or post-implantation loss or sex ratio. Overall, maternal NOAEL was determined to be 500 ppm (on the basis of mean body weight gain) while fetal NOAEL was greater than the highest concentration tested.

A similar study was conducted in New Zealand rabbits exposed to 0, 500, 1200 or 2300 ppm, 6 hours/day from gestation days 6-18 (Darmer et al., 1997). Similar to rats, there was a statistically significant decrease in mean body weight gain on gestation days 6-18 for the 2300 ppm dams. No other treatment-related effects were reported. There were no treatment-related effects on gestational parameters and malformations. Maternal NOAEL was determined to be 1200 ppm while fetal NOAEL was determined to be greater than highest concentration tested.

Justification for classification or non-classification

No developmental toxicity was reported in two GLP developmental toxicity studies of isopropyl benzene (a C9 aromatic hydrocarbon) in rats and rabbits. Effects found in the mouse inhalation developmental study was most likely related to maternal effects. The mouse inhalation developmental toxicity study caused maternal toxicity at 500 ppm, as evidenced by a decrease in maternal weight gain, possibly secondary to subclinical CNS depression; at this concentration there was also decreased foetal body weight, but no other evidence of developmental toxicity. At the next lowest dose, 100 ppm, there was no evidence of either maternal or developmental toxicity. The mouse may be more sensitive than the rat because of an increased respiratory rate, per kg bdy wt, would result in an increased internal dose.Classification as a repro/developmental toxicant under GHS is not required, because the effect (reduced body weight) was minor and reversible, and occurred only at a concentration which produced similar effects in the dams.”

Additional information