Hydrocarbons, C9, aromatics

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Hydrocarbons, C9 Aromatics:

Inhalation: Hydrocarbons, C9, aromatics, were examined for toxicity in a three-generation reproductive toxicity study. The NOAEC (inhalation) for reproductive toxicity for the P, F1, and F2 generation was ≥1500 ppm.

 

Hydrocarbons, C10 Aromatics:

Oral: N-butylbenzene, a C10 aromatic hydrocarbon, was examined for toxicity in a two-generation reproductive toxicity study. The NOAEL was determined to be ≥300 mg/Kg bw/day.

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Hydrocarbons, C9 Aromatics:

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.

 

Hydrocarbons, C10 Aromatics:

N-butylbenzene, a C10 aromatic hydrocarbon, was examined for toxicity in a two-generation reproductive toxicity study. N-butylbenzene was administered by oral gavage at dose levels of 0, 30, 100, and 300 mg/Kg/day to groups of Crj: CD (SD) IGS rats (24 males and 24 females per group) over 2 generations, and the effects on fertility of the parental animals and development/growth of the offspring were investigated. It was concluded that n-butylbenzene did not induce reproductive toxicity in the F1 parental animals and no effects on the endocrine system were observed. Therefore, the NOAEL was determined to be ≥300 mg/Kg bw/day. 

Based on this study, C10-C12 Aromatic Hydrocarbons, are not expected to be reproductive toxicants.

Effects on developmental toxicity

Description of key information

Hydrocarbons, C9 Aromatics:

Maternal (inhalation) NOAEC = 100 ppm

 

Developmental (inhalation) NOAEC = 100 ppm

 

Hydrocarbons, C10 Aromatics:

Maternal (oral) NOAEL = 150 mg/Kg/day

 

Developmental (oral) NOAEL >450 mg/Kg/day

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Hydrocarbons, C9 Aromatics:

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 of isopropyl benzene 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.

Hydrocarbons, C10 Aromatics:

The developmental toxicity of naphthalene was evaluated in in rats and rabbits (Naphthalene, a C10 aromatic substance was used as analogue read-across for all C10 aromatic fluids). Rats were administered 0, 50, 150 or 450 mg/Kg/day via oral gavage on gestation days 6-15 (NTP, 1991). Naphthalene produced visible evidence of central nervous system depression (lethargy, prone body posture and slow breathing) in all dose groups, although the effects subsided in the 50 and 150 mg/Kg dose groups before the end of the treatment period. Naphthalene exposure caused a statistically significant decrease in maternal body weight gain in the mid and high dose groups. However, the authors reported that naphthalene was not fetotoxic or teratogenic at any dose as there were no significant differences in the average number of corpora lutea/dam, implantation sites/litter, live fetuses/litter and fetal body weights. Maternal NOAEL was determined to be <50 mg/Kg/day on the basis of central nervous system depression. Developmental/fetal NOAEL was determined to be greater than 450 mg/Kg/day although increasing trends towards decreased fetal weight and increased malformations suggested that the true developmental/fetal LOAEL was close to the highest dose tested.

 

In the rabbit study, dams were administered 0, 20, 80 or 120 mg/Kg/day by oral gavage on gestation days 6-19 (NTP, 1992). Dose levels were lower than those in the rat as a result of significant mortality in rabbits (40% mortality) with administration of 150 mg/Kg/day in a range-finding study. No treatment-related effects were reported in the dams or fetus. NOAEL for maternal and developmental/fetal effects was greater than the highest dose tested.

Justification for classification or non-classification

Based on the results from read across studies, Hydrocarbons, C9, aromatics do not warrant classification as a reproductive or developmental toxicants under Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).