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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route
Dose descriptor:
2 106 mg/m³
Additional information

Groups of 30 males and 30 females CD rats, designed as P generation, were exposed to vapor of monochlorobenzene (MCB) at target concentrations of 0 , 50, 150, or 450 ppm (0, 234, 702 or 2106 mg/m³) for 10 weeks prior to mating and during mating, gestation, and lactation. The progeny of the P generation was designed as the F1 generation and groups of 30 male and 30 female F1 animals were exposed to the same concentration of MCB as the F0 parents. Exposure of F1 animals was initiated prior to the mating and through mating, gestation, and lactation. All F2 pups were observed through weaning at which time they were killed.

Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues.

No mortality was observed during the course of this study. No adverse effect of treatment was evident on body weight, food consumption, and physical observation. Mating and fertility indices for males and females for both generations appeared unaffected by treatment.The slightly reduced pregnancy indices mainly at the highest concentration level (0, 50, 150, 450 ppm: P: 90, 100, 93.1, 86.7 F1: 80, 100, 79.3, 89.3) were within the historical control data of the testing facility in the respective time interval (CD rat at Bio/dynamics, Inc., 1978 -1984, representing pregnancy rates for a total of 16 studies containing a total of 62 litter intervals:

mean = 85.0 % [67.9 % to 100.0 %]. Body weights and food consumption for all treated groups were comparable to controls during the growth period. Maternal body weight data during gestation and lactation were also comparable between the control and treated groups

Overall, reproductive performance, fertility and development of pups were not affected by treatment with monochlorobenzene yielding a NOAEC of 450 ppm (corresponding to 2106 mg/m³) for reproduction and development.

However, post mortem examinations revealed significantly elevated absolute and relative liver weights in P and F1 male and female rats at 150 and 450 ppm and at 50 ppm in F1 males accompanied by hepatocellular hypertrophy. In addition, renal changes (tubular dilation with eosinophilic material, interstitial nephritis, and foci of regenerative epithelium) were observed mainly in F0 and F1 male rats. The significance of reported degeneration of the testicular germinal epithelium in male rats at 450 ppm is unclear because no histopathological correlate is reported. Thus, the LOAEC (systemic toxicity) is considered to be 50 ppm (corresponding to 234 mg/m³).

Short description of key information:
In a two generation reproductive toxicity study in accordance to OECD TG 416 male and female CD rats were exposed to 0, 50, 150 and 450 ppm ( corresponding to 0, 234, 702, 2106 mg/m³) monochlorobenzene. The exposure to monochlorobenzene has no adverse effect s on reproductive performance or fertility of male and female rests despite the availabliity of systemic toxicity:
NOAEC ( male, female, reproduction and fertility): 450 ppm (2106 mg/m³); LOAEC male, female, systemic): 50 ppm (234 mg/m³)

Effects on developmental toxicity

Description of key information
The embryotoxic and teratogenic potential of inhaled chlorobenzene was evaluated in rats and rabbits  
Fischer 344 rats and New Zealand White rabbits were exposed to 0, 351, 983, or 2761 mg/m³ chlorobenzene via inhalation for 6 hr/day during the period of major organogenesis. In a second study with rabbit, additional groups were exposed to 0, 47, 140, 351, or 2761 mg/m³ using the same experimental conditions. Overall, based on the available results in rats and rabbits the NOAEC (development) is considered to be 450 ppm ( corresponding to 2761 mg/m³ ).
Effect on developmental toxicity: via inhalation route
Dose descriptor:
2 761 mg/m³
Additional information

The embryotoxic and teratogenic potential of inhaled chlorobenzene was evaluated in rats and rabbits (John et al, 1984). Fischer 344 rats and New Zealand White rabbits were exposed to 0, 351, 983, or 2761 mg/m³ chlorobenzene via inhalation for 6 hr/day during the period of major organogenesis. To further evaluate the effects of chlorobenzene in rabbits, additional groups were exposed to 0, 47, 140, 351, or 2761 mg/m³ under the same experimental conditions

With respect to the studies in rats monochlorobenzene vapor inhalation during gestation was not embryotoxic or teratogenic.

In the first study with rabbits, evidence of slight maternal toxicity was observed among rabbits exposed to 983 or 2761 mg/m³; the absolute and relative weights of the liver were significantly increased in these groups. No statistically identified or consistent effects on body weight or body weight gain were observed in any of the exposure groups of rabbits. The pregnancy rate in rabbits was not altered by exposure to chlorobenzene. At the same time any adverse effects on the mean litter size or the incidence of implementations which were undergoing resorption were observed.

In the second study in rabbits, exposure to 2761 mg/m³ produced an increase in the liver weight of maternal animals. A significant increase in the percentage of implantations undergoing resorption was observed in the 2761 mg/m³group. In this group, 61% of the litters (12% of fetuses) contained resorptions compared to 41% of the litters for the controls (6% of the fetuses). The resorption rate was not signifcantly altered at the lower exposure concentrations.

A significant increase in the mean fetal crown-rump lenght was observed in litters from the 983 mg/m³ group, but this increase was not considered to be of toxicological importance. Mean fetal body weights of litters from the exposed groups were not significantly altered. In the first study, exposure of rabbits to 0, 351, 983, or 2761 mg/m³ chlorobenzene resulted in a variety of malformations in all groups, at an incidence slightly higher than historical controls. Forelimb flexure, the malformation most often observed occurred more often among controls than among any of the treatment groups as malformations of the skeletal system. The latter induced hemivertebrae, missing or fused vertebrae, crooked long bones, and a variety of rib malformations. However, there were several cases of external and visceral malformations which were scattered among exposed groups. For instance spina bifica (single case) and low incidence of heart anomalies were observed in the 210 and 590 ppm (983 and 2761 mg/m³) groups, whereas these malformations were not observed among the concurrent control group. In the second study , fetal body measurements were not adversely affected by exposure by chlorobenzene. The incidence of malformations from the exposed groups, when cosidered individually or collectively, was not significantly increased compared to the control group. Fetuses with external soft tissue, and the skeletal malformations were observed among all groups including controls.

Overall, the NOAEC was deduced to more than 2761 mg/m3.

Justification for classification or non-classification

No classification/labelling is required..

Additional information